06 influenza olson 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Effectiveness of Maternal Influenza Vaccination during Pregnancy
against Influenza- associated Hospitalizations & ED Visits in Infants <6
Months of Age
Samantha M. Olson, MPH
NVSN Flu Lead/ EpidemiologistInfluenza Prevention and Control Team (IPACT)
Influenza Division
ACIP Meeting: Influenza Session
October 25, 2023
•Influenza virus infection during pregnancy is associated with severe disease and may be associated
with some adverse birth outcomes . Background
•Influenza vaccination during pregnancy can protect infants <6 months of age, who are not age -eligible
for vaccination.
•Randomized control trials conducted outside of the US showed a maternal vaccine efficacy against
laboratory -confirmed influenza in infants of 30-63%
•There is a lack of real -world, multi -center, multi -season, and US data on maternal vaccine effectiveness (VE)
against medically -attended influenza in infants•Receipt of inactivated influenza vaccine during pregnancy is safe and effective.
•Since the COVID -19 pandemic, influenza vaccination uptake during pregnancy is ~5-15% lower than pre -
pandemic seasons.
Current ACIP Wording (As of 2021- 2022 Influenza Season):
–Pregnant persons in the third trimester: Vaccination during July and August can be considered for
pregnant persons who are in the third trimester because vaccination might reduce risk for influenza
illness in their infants during the first months after birth, when they are too young to receive
influenza vaccine (33 –36). For pregnant persons in the first or second trimester during July and
August, waiting to vaccinate until September or October is preferable , unless there is concern that
later vaccination might not be possible.Prevention and Control of Seasonal Influenza with Vaccines:
Recommendations of the Advisory Committee on Immunization Practices
https://www.cdc.gov/mmwr/volumes/71/rr/rr7101a1.htm
https://www.cdc.gov/mmwr/volumes/70/rr/rr7005a1.htm?s_cid=rr7005a1_w
Influenza Division  |NCIRDQuestion:
Does maternal influenza vaccination during pregnancy
reduce influenza -associated hospitalizations and
emergency department (ED) visits in infants <6 months
of age?
NVSN* Pediatric Inpatient & ED Network Sites
Seattle Children’s
Cincinnati
Children’sChildren’s Hospital of
Pittsburgh
Vanderbilt University
Nashville
Texas Children’s Hospital
Houston
Children’s Mercy Hospital
Kansas City
University of Rochester
*NVSN --New Vaccine Surveillance Network
•Enrollment: Infants <6 months of age admitted to the hospital or emergency department during 4 influenza seasons
(from Fall 2016 through Spring 2020) at 7 pediatric medical centers within the NVSN
•Cases:
•Tested positive for influenza by RT -PCR with acute respiratory illness (ARI) symptoms within 10 days of symptom
onset
•Controls: Tested negative for influenza with ARI symptoms
•Design: Test-negative design
•Odds of maternal influenza vaccination ≥14 days prior to delivery in case infants with influenza were compared
to control infants with non -influenza respiratory illness
•Vaccination status: Vaccination was defined as influenza vaccine received during pregnancy
•Documented (registry or providers) or self -reported vaccination with timing (date or trimester) during pregnancy
•Data on maternal influenza infection during pregnancy was not collected
•Analysis: VE= (1 – adjusted odds ratio) x 100%
•Adjusted for infant age, NVSN site, and calendar timeMethods
Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality

Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality

Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality

Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality

Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality

Figure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and
influenza seasonality

Influenza Division  |NCIRDResults
4,049 infants <6 months of age enrolled
between the 2016- 2017 through the
2019- 2020 flu seasons from 7 pediatric
medical institutions
3,764 infants included
2,007 (53%) born to vaccinated mothers
1,757 (47%) born to unvaccinated
mothers285 Were excluded (21 cases, 264 controls)
92Born to mothers vaccinated <14 days
prior to delivery (8 cases, 84 controls)
193 Had unknown vaccination timing (13
cases, 180 controls)
223 case -infants tested positive for influenza
94 (42%) born to vaccinated mothers
129 (58%) born to unvaccinated mothers3,541 control -infants tested negative for influenza
1,913 (54%) born to vaccinated mothers
1,642 (46%) born to unvaccinated mothers
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Median age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)
Age group –no. (%)
0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)
3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)
Female sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)
Race and ethnic group –no./ total no. (%)
White, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)
Black, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)
Hispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)
Other21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)
At least one underlying condition in
infants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Median age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)
Age group –no. (%)
0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)
3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)
Female sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)
Race and ethnic group –no./ total no. (%)
White, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)
Black, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)
Hispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)
Other21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)
At least one underlying condition in
infants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)Case -infants and those born to unvaccinated mothers were older than control -
infants and those born to vaccinated mothers.
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Median age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)
Age group –no. (%)
0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)
3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)
Female sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)
Race and ethnic group –no./ total no. (%)
White, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)
Black, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)
Hispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)
Other21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)
At least one underlying condition in
infants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)Infant case status and maternal vaccination status differed by race and ethnic
group .
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Median age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)
Age group –no. (%)
0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)
3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)
Female sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)
Race and ethnic group –no./ total no. (%)
White, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)
Black, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)
Hispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)
Other21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)
At least one underlying condition in
infants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)More infants born to vaccinated mothers were breastfeeding on enrollment,
and more infants born to unvaccinated mothers had underlying conditions .
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Preterm birth (born <37 weeks gestation)
–no./ total no. (%)37/223 (17) 613/3535 (17) 315/2004 (16) 335/1754 (19)
35-<37 weeks 20/36 (56) 319/600 (53) 167/307 (54) 172/329 (52)
30-34 weeks 14/36 (39) 219/600 (37) 122/307 (40) 111/329 (34)
≤29 weeks 2/36 (6) 62/600 (10) 18/307 (6) 46/329 (14)
NVSN sites– no. (%)
Nashville 38 (17) 708 (20) 361 (18) 385 (22)
Rochester 14 (6) 358 (10) 213 (11) 159 (9)
Cincinnati 42 (19) 345 (10) 198 (10) 189 (11)
Seattle 26 (12) 359 (10) 281 (14) 104 (6)
Houston 39 (17) 797 (23) 391 (19) 445 (25)
Kansas City 35 (16) 317 (9) 174 (9) 178 (10)
Pittsburgh 29 (13) 657 (19) 389 (19) 297 (17)
Season of enrollment – no. (%)
2016- 2017 49 (22) 778 (22) 462 (23) 365 (21)
2017- 2018 60 (27) 829 (23) 429 (21) 460 (26)
2018- 2019 45 (20) 986 (28) 560 (28) 471 (27)
2019- 2020 69 (31) 948 (27) 556 (28) 461 (26)
CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Preterm birth (born <37 weeks gestation)
–no./ total no. (%)37/223 (17) 613/3535 (17) 315/2004 (16) 335/1754 (19)
35-<37 weeks 20/36 (56) 319/600 (53) 167/307 (54) 172/329 (52)
30-34 weeks 14/36 (39) 219/600 (37) 122/307 (40) 111/329 (34)
≤29 weeks 2/36 (6) 62/600 (10) 18/307 (6) 46/329 (14)
NVSN sites– no. (%)
Nashville 38 (17) 708 (20) 361 (18) 385 (22)
Rochester 14 (6) 358 (10) 213 (11) 159 (9)
Cincinnati 42 (19) 345 (10) 198 (10) 189 (11)
Seattle 26 (12) 359 (10) 281 (14) 104 (6)
Houston 39 (17) 797 (23) 391 (19) 445 (25)
Kansas City 35 (16) 317 (9) 174 (9) 178 (10)
Pittsburgh 29 (13) 657 (19) 389 (19) 297 (17)
Season of enrollment – no. (%)
2016- 2017 49 (22) 778 (22) 462 (23) 365 (21)
2017- 2018 60 (27) 829 (23) 429 (21) 460 (26)
2018- 2019 45 (20) 986 (28) 560 (28) 471 (27)
2019- 2020 69 (31) 948 (27) 556 (28) 461 (26)More infants born to unvaccinated mothers were born preterm.
Preterm birth (born <37 weeks
gestation) –no./ total no. (%)35/216 (16) 612/3597 (17) 310/2051 (15) 337/1762 (19)
35-<37 weeks 19/34 (56) 318/602 (53) 166/305 (54) 171/331 (52)
30-34 weeks 14/34 (41) 219/602 (36) 120/305 (39) 113/331 (34)
≤29 weeks 1/34 (3) 65/602 (11) 19/305 (6) 47/331 (14)CharacteristicCase status Maternal Vaccination Status
Case -infants
(N=223)Control -infants
(N=3541)Vaccinated
(N=2007)Unvaccinated (N=1757)
Preterm birth (born <37 weeks gestation)
–no./ total no. (%)37/223 (17) 613/3535 (17) 315/2004 (16) 335/1754 (19)
35-<37 weeks 20/36 (56) 319/600 (53) 167/307 (54) 172/329 (52)
30-34 weeks 14/36 (39) 219/600 (37) 122/307 (40) 111/329 (34)
≤29 weeks 2/36 (6) 62/600 (10) 18/307 (6) 46/329 (14)
NVSN sites– no. (%)
Nashville 38 (17) 708 (20) 361 (18) 385 (22)
Rochester 14 (6) 358 (10) 213 (11) 159 (9)
Cincinnati 42 (19) 345 (10) 198 (10) 189 (11)
Seattle 26 (12) 359 (10) 281 (14) 104 (6)
Houston 39 (17) 797 (23) 391 (19) 445 (25)
Kansas City 35 (16) 317 (9) 174 (9) 178 (10)
Pittsburgh 29 (13) 657 (19) 389 (19) 297 (17)
Season of enrollment – no. (%)
2016- 2017 49 (22) 778 (22) 462 (23) 365 (21)
2017- 2018 60 (27) 829 (23) 429 (21) 460 (26)
2018- 2019 45 (20) 986 (28) 560 (28) 471 (27)
2019- 2020 69 (31) 948 (27) 556 (28) 461 (26)Vaccination status differed by NVSN site and flu season of enrollment.
Maternal Vaccine Effectiveness against Influenza -associated
Hospitalizations and Emergency Department Visits in Infants <6 months
Overall maternal vaccine effectiveness against influenza hospitalizations
and emergency department visits in infants <6 months of age is 34%
Maternal vaccine effectiveness was higher among infants <3 months,
vaccinated during the third trimester , and against hospital admission
Maternal vaccine effectiveness was consistent with other VE estimates by
influenza type and subtype for the 2016 -17 through 2019 -20 flu seasons.

Maternal Vaccine Uptake
Influenza vaccine uptake during
pregnancy is nationally consistent
but suboptimal.
Benefits to Infants
Maternal vaccination was
associated with reduced odds of
influenza hospitalizations & ED
visits in infants <6 months of age.
Highest Vaccine Effectiveness
VE was greatest among infants <3
months of age , those born to
mothers vaccinated during their
third trimester of pregnancy, and
against influenza -associated
hospitalizations .
Summary Policy Implications
Currently, there are no anticipated
changes to vaccination timing
recommendations during
pregnancy.
Influenza Division  |NCIRD
Acknowledgments
Leila C. Sahni
Natasha B. Halasa
Laura S. Stewart
Marian G. Michaels
John V. Williams
Janet A. Englund
Eileen J. Klein
Mary A. Staat
Elizabeth P . Schlaudecker
Jennifer E. SchusterRangaraj Selvarangan
Geoffrey A. Weinberg
Peter G. Szilagyi
Manish M. Patel
Julie A. Boom
Flor M. Muñoz
NVSN Research Teams & Study Participants

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Effectiveness of Maternal Influenza Vaccination during Pregnancy  against Influenza- associated Hospitalizations & ED Visits in Infants <6  Months of Age Samantha M.…


07 influenza kondor 508

1
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
Update on Influenza B/Yamagata
Surveillance
Rebecca Kondor, PhD
Interim Director, WHO Collaborating Center for Surveillance,
Epidemiology and Control of Influenza
Lead, Genomics Analysis Team
Virology, Surveillance and Diagnosis Branch –Influenza Division –NCIRD
2
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
WHO’s Global Influenza Surveillance and Response System (GISRS)
The mission of GISRS is to protect people from
the threat of influenza by continuously functioning as a:
•Global mechanism of surveillance,
preparedness and response for seasonal, pandemic and zoonotic influenza
•Global platform for monitoring influenza
epidemiology and disease
•Global alert for novel influenza viruses and
other respiratory pathogens
WHO GISRS
3
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
•GISRS National Influenza Centers (NICs)
•Collect respiratory specimens from
established networks of physicians, health
care centers or other sentinel sites,
and/or they solicit influenza virus -positive
samples
•Perform initial influenza virus detection, typing and subtyping
•CDC develops and manufactures assays which are distributed by IRR
•Share a subset of representative influenza virus specimens and/or isolates with
WHO CCs for antigenic and genetic
characterization and creation of candidate vaccine viruses
•Report to WHO RespiMart
•epidemiological information FluID
•laboratory results to FluNet
152 WHO National Influenza Centers in 129 Member States
•7 WHO Collaborating Centers for Influenza
•4 Essential Reference Laboratories
•12 WHO H5 Reference LaboratoriesWHO’s Global Influenza Surveillance and Response System (GISRS)
WHO GISRS
4
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
WHO GISRS
Update on Influenza B/Yamagata Surveillance
FluNet data can be delineated by surveillance site type
•Sentinel –Sentinel surveillance systems collect high -quality data in a timely manner, systematically and routinely
from sentinel surveillance sites representative of the population under surveillance. Case definition (ILI, SARI, ARI)
and populations differ by country (e.g., only certain age groups, health -care workers, hospitalized)
•Non -sentinel –Data reported in this category may include outbreak investigation, universal testing, testing at point
of care or other systems apart from sentinel surveillance
•Type not defined –These data may include sentinel or non -sentinel surveillance sources or both
The level of information reported to FluNet depends on the country and the laboratory where testing occurs
•Rapid tests only determine influenza A or B
•Large clinical and hospital laboratories often only determine influenza A or B, with some assays also determining influenza A subtype
•A higher proportion of viruses from sentinel surveillance will include influenza A and B subtyping results
WHO GISRS
5
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
Types of Assays for B/lineage at NIC:
•Serology Based
•CDC WHO Kit
•anti-B/Vic and anti -B/Yam goat antiserum –created by WHO CC Atlanta available in CDC IRR
•52 countries recently ordered kits
•HI Assay –anti-B/Vic and anti -B/Yam ferret antiserum provided by WHO CCs
•Molecular Based
•CDC RT- PCR B Lineage Assay RUO -created by WHO CC Atlanta available in CDC IRR
•104 countries recently ordered kits
•Other RT -PCR assays
•Sequencing (sanger or NGS) –clinical specimens or viral isolates
GISRS NICs also submit specimens to WHO CCs for virus characterization
•Using the above methods B lineage is attempted for all viruses received
•WHO CC have confirmed ZERO circulating B/Yamagata lineage viruses collected after March 2020
•Those reported as B/Yamagata were determined to be incorrectly lineage reports, negative for influenza
or B/Yamagata component of LAIV
Non-sentinel surveillance may use different assays than those listed above.WHO GISRSWHO GISRS
Update on Influenza B/Yamagata Surveillance
6
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
WHO GISRS Influenza Surveillance
September 2017 -August 2020
Northern Hemisphere
Southern Hemisphere•Influenza B/Yamagata lineage viruses were the
predominant B/lineage circulating during the 2017- 18 Northern Hemisphere and 2018
Southern Hemisphere seasons
•2018- 2019 Northern Hemisphere had much less
B activity overall and B/Victoria lineage viruses predominated
•2019 Southern Hemisphere showed regional differences in B/lineage circulation with B/Yamagata mainly circulating in South America
•2019- 20 Northern Hemisphere season began
with an early B/Victoria lineage peak, followed by A(H1N1)pdm09
•COVID -19 Pandemic and its mitigation saw a
drop in influenza virus detection and circulation
GIP FLUNET PowerBI

7
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
WHO GISRS Influenza Surveillance
September 2020 -August 2023
Northern Hemisphere
Southern Hemisphere•GISRS NICs continued influenza surveillance
during the COVID -19 Pandemic
•Influenza continued to be detected but without seasonal peaks in epidemics until late 2021
•All influenza B activity due to B/Victoria lineage
•February 1 – August 31, 2023
•1/3 of all viruses detected by GISRS were influenza B
•Parts of Northern Hemisphere saw second peak of activity due to B/Victoria and A(H1N1)pdm09 viruses
•Southern Hemisphere 2023 season co -circulation
of B/Victoria and A(H1N1)pdm09 viruses
GIP FLUNET PowerBI

8
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
Countries reporting influenza B detections to FluNet February 1 -August 31, 2023
All Types of Surveillance
GIP FLUNET PowerBI Map made from data available at
9
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
Virus Detections by B lineage reported to FluNet
All Types of Surveillance
Data source: GIP FLUNET PowerBI1 B/Yamagata reported (non -sentinel surveillance)
1 February 2023 through 31 August 2023
1 B/Yam non -sentinel surveillance
10
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
Virus Detections by subtype reported to FluNet
Sentinel Surveillance
Data source: GIP FLUNET PowerBINo B/Yamagata detected in GISRS sentinel surveillance
1 February 2023 through 31 August 2023
11
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
WHO GISRS Influenza B/Lineage Reports
February 1 –August 31, 2023
As of 31 August 2023•99,453 influenza B viruses detected in 139 countries
•15,878 influenza B viruses had results from B/lineage assays reported to FluNet from all surveillance
types
•15 initial reports to GISRS as B/Yamagata underwent confirmation by WHO CCs and WHO Global
Influenza Programme
•13 were confirmed as B/Victoria Lineage or negative for influenza and their FluNet records were
updated accordingly
•2 did not have specimens available for confirmation testing at a WHO CC (one was not reported to FluNet ). These specimens did not yield viral isolates or sequence data.
•All influenza B viruses received by WHO CCs were B/Victoria lineage
•Genomic surveillance of influenza B viruses found only genet segments derived from circulating B/Victoria lineage
•This data supports that B/Yamagata viruses are extremely rare and not responsible for recent epidemics
•The majority of B/Yamagata reports are due to an incorrect lineage determination
12
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
WHO vaccine recommendations for the
Southern Hemisphere 2024
WHO recommendation and technical reports available on the WHO web site: https://www.who.int/teams/global -influenza -programme/vaccines/who -recommendations It is recommended that vaccines licensed for use in the 2024 southern hemisphere influenza season
contain the following:
Trivalent: Egg-based Vaccines
-an A/Victoria/4897/2022 (H1N1)pdm09- like virus antigen* ;
-an A/Thailand/8/2022 (H3N2) -like virus antigen** ; and
-a B/Austria/1359417/2021 (B/Victoria lineage) -like virus.
Trivalent: Cell- or recombinant- based Vaccines
-an A/Wisconsin/67/2022 (H1N1)pdm09- like virus antigen*;
-an A/Massachusetts/18/2022 (H3N2) -like virus antigen**; and
-a B/Austria/1359417/2021 (B/Victoria lineage) -like virus antigen.
Quadrivalent: egg-or cell culture -or recombinant- based vaccines
-Above 3 components; and a B/Phuket/3073/2013 (B/Yamagata lineage) -like antigen.
* Different from that recommended for the 2023 southern hemisphere season but the same as the NH 2023 -24 recommendation.
** Different from that recommended for the 2023 southern hemisphere season and from NH 2023 -24 recommendation.
13
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
WHO Vaccine Recommendations Summary
•The absence of confirmed detection of naturally occurring B/Yamagata lineage viruses is
indicative of very low risk of infection by B/Yamagata lineage viruses.
•While influenza vaccines are safe and effective, the manufacture and use of inactivated and live attenuated vaccines containing B/Yamagata lineage viruses pose a theoretical risk of reintroduction of B/Yamagata lineage virus into the population. This risk can be mitigated by
the removal of B/Yamagata lineage viruses from the vaccines.
•It was the opinion of the WHO influenza vaccine composition advisory committee that the
inclusion of a B/Yamagata antigen as a component of influenza vaccines is no longer
warranted, and every effort should be made to exclude this component as soon as practically
possible.
•The committee recognizes that national or regional authorities are responsible for approving the composition and formulation of vaccines used in each country and should consider the
use & relative benefit(s) of trivalent or quadrivalent influenza vaccines.
14
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
Ongoing Influenza B Surveillance
•GISRS laboratories will continue to be supported by CDC for influenza testing, typing
and influenza A/B subtyping through reagents available in IRR
•GISRS laboratories and WHO CCs will continue to perform B/lineage testing
•Any reports of B/Yamagata viruses will be confirmed by WHO CCs
•For the 2023- 2024 season, US public health labs will continue to perform assays to
determine B/lineage –all B/Yamagata detections will be sent to CDC for confirmation.
•All US specimens with RT -PCR results of a mix of influenza A and B will also be sent to
CDC for confirmation. The majority of previous results of A/B mixtures were from individual vaccinated with LAIV.
15
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,
Influenza Division, National Center for Immunization and Respiratory Diseases
Support and Disclaimer
The findings and conclusions in this report are those of the authors and do not necessarily represent
the official position of the Centers for Disease Control and Prevention.
These projects have been funded in part with federal funds from US Health and Human
Services (National Institutes of Health, Centers for Disease Control, and the Biomedical
Advanced Research and Development Authority).

Summary: 1 WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,   Influenza Division, National Center for Immunization and Respiratory Diseases Update on Influenza B/Yamagata  Surveillance Rebecca Kondor, PhD Interim Director, WHO Collaborating Center for Surveillance,  Epidemiology and Control of Influenza Lead, Genomics Analysis Team Virology, Surveillance and Diagnosis Branch –Influenza Division –NCIRD 2 WHO Collaborating Center for Surveillance, Epidemiology and Control…


01 RSV Mat Ped Long 508

1
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Maternal/Pediatric Respiratory Syncytial Virus (RSV)
Work Group
Sarah S. Long, MD
Chair, Maternal/Pediatric RSV Work Group
ACIP General Meeting
September 22, 2023
2Each year in U.S. children aged less than 5 years,
RSV is associated with…
~1,500,0003
outpatient visits~520,0003
emergency department visits58,000 –80,0003,4
hospitalizations100–3001,2
deaths
1Thompson et al, JAMA, 2003 ; 2Hansen et al, JAMA Network Open, 2022 ; 3Hall et al, NEJM, 2009 ; 4McLaughlin et al, J Infect Dis, 2022 (*estimate 80,000 hospitalizations in infants
<1y)
3▪Most (68%) infants are infected in the first year of life and
nearly all (97%) by age 2 years2
▪2-3% of young infants will be hospitalized for RSV3,4,5
▪RSV is a common cause of lower respiratory tract infection
in infants
▪Highest RSV hospitalization rates occur in first months of
life and risk declines with increasing age in early
childhood3,5
▪79% of children hospitalized with RSV aged <2 years had no
underlying medical conditions3RSV is the leading cause of hospitalization in U.S.
infants1
1Suh et al. JID 2022 ; 2Glezen et al, Arch Dis Child, 1986 ; 3Hall et al, Pediatrics, 2013 ; 4Langley & Anderson, PIDJ, 2011 ; 5CDC NVSN data
Image: Goncalves et al. Critical Care
Research and Practice 2012
4▪Epidemiology and burden of RSV in infants
▪Virology and immunology of RSV
▪Safety and efficacy of RSVpreF
▪Cost effectiveness analysis for RSVpreF –CDC model
▪Cost effectiveness analysis for RSVpreF –Comparison with manufacturer model
▪Evidence to Recommendations framework for RSVpreF
▪Clinical considerations for RSVpreFPrevious maternal/pediatric RSV ACIP presentations on
RSVpreF vaccine
5▪On August 21, 2023, FDA approved Pfizer RSVpreF vaccine for use in pregnant people for the
prevention of RSV lower respiratory tract disease and severe lower respiratory tract disease in
infants from birth to 6 months of age
▪Approved as a single dose to be given at 32 –36 weeks gestation
–In phase 2b and 3 trials, vaccination was given during 24 –36 weeks gestation
–A numerical imbalance in preterm births was observed in RSVpreF vaccine compared to
placebo recipients in two clinical studies
–Available data are insufficient to establish or exclude a causal relationship between preterm
birth and RSVpreF
–Additionally, a numerical imbalance in hypertensive disorders of pregnancy was observed in
RSVpreF vaccine compared to placebo recipientsFDA approval for RSVpreF vaccine
FDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants | FDA
Package Insert -ABRYSVO (STN 125768) (fda.gov)
August 21, 2023 Approval Letter -ABRYSVO (STN 125768) (fda.gov)
6▪Starting dosing at 32 weeks gestation can reduce the potential risk of and complications from
preterm birth until additional safety data are available
–Avoids the risk of extremely preterm births, where there is substantive morbidity and
mortality, and very preterm births
–Similar vaccine efficacy in 32 -36 weeks gestation compared to the overall study population
▪FDA has required the manufacturer to conduct post -marketing studies to assess preterm birth
and hypertensive disorders of pregnancy, including pre -eclampsiaFDA approval for RSVpreF vaccine (cont.)
FDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants | FDA
Package Insert -ABRYSVO (STN 125768) (fda.gov)
August 21, 2023 Approval Letter -ABRYSVO (STN 125768) (fda.gov)
7▪On August 3, 2023, ACIP recommended nirsevimab for RSV prevention in infants
–Infants aged <8 months born during or entering their first RSV season are
recommended to receive one dose of nirsevimab (50 mg for infants <5 kg and 100
mg for infants ≥5 kg)
–Children aged 8 –19 months who are at increased risk of severe RSV disease and
entering their second RSV season are recommended to receive one dose of
nirsevimab (200 mg) RSVpreF vaccine is one of two available preventive
products for RSV in infants
8▪A person develops active immunity from infection or vaccination
–Triggers an immune response
–Immunologic memory provides prolonged protection that may be lifelong
▪Passive immunity is transfer of preformed antibody produced externally to provide
protection to the recipient
–From mother to baby through transplacental or breastmilk transfer
–Direct administration of antibodies, such as IVIG or monoclonal antibodies
–Provides temporary protection that wanes with timeBoth nirsevimab and maternal RSV vaccine provide passive
immunity
IVIG= Intravenous Immunoglobulin Therapy
https://www.cdc.gov/vaccines/vac -gen/immunity -types.htm
9Agenda: Friday September 22, 2023
RSVpreF Vaccine Safety Surveillance in Pregnancy from
The Vaccine Safety DatalinkDr. Malini DeSilva (HealthPartners
Institute)
Maternal RSV vaccine safety monitoring in the Vaccine
Adverse Event Reporting System (VAERS) and V -safeDr. Pedro Moro (CDC/NCEZID)
Economic analysis of RSVpreF maternal vaccination Dr. David Hutton (University of
Michigan)
Economics of Preventing Respiratory Syncytial Virus
Disease among US Infants by Maternal Vaccination Prior
to BirthDr. Ismael Ortega -Sanchez
(CDC/NCIRD)
Evidence to Recommendations Framework Updates:
Pfizer Maternal RSVpreF VaccineDr. Katherine Fleming -Dutra
(CDC/NCIRD)
10Agenda: Friday September 22, 2023 (cont.)
Updated clinical considerations for use of both
nirsevimab and Pfizer RSVpreF vaccineDr. Jefferson Jones (CDC/NCIRD)
Implementation considerations for maternal RSV
vaccineDr. Georgina Peacock (CDC/NCIRD)
Vaccines for Childrens Resolution Dr. Jeanne Santoli (CDC/NCIRD)
Break
Public Comment
Break
Vote on recommendation and Vaccines for Children
Adult and Pediatric Immunization Schedule Addendum Dr. Sarah Schillie (CDC/NCIRD)
11▪Should Pfizer RSVpreF vaccine be recommended for pregnant people to be given
during 32 through 36 weeks gestation to prevent RSV lower respiratory tract infection
in infants?Policy Question
12Work group members (External)
ACIP Members
Sarah Long (chair)
Pablo Sanchez
Oliver Brooks
Camille KottonConsultants
Cody Meissner (Dartmouth Geisel School of Medicine)
Helen Chu (University of Washington)
Natasha Halasa (Vanderbilt University)
Denise Jamieson (Emory University School of Medicine)
Daniel Feikin (World Health Organization)
Carol Baker (University of Texas Health Science Center)
Kevin Ault (Western Michigan University)Liaisons
James McAuley (IDSA)
Patsy Stinchfield (NFID)
Brenna L. Hughes (ACOG)
Nicole Chaisson (AAFP)
Sean O’Leary (AAP)
Jennifer Schuster (PIDS)
Molly Howell (AIM)GRADE/ EtR Consultants
Doug Campos -Outcalt
Rebecca MorganEx Officio Members
Rachel Zhang (FDA -CBER)
Nicholas Geagan (FDA -CBER)
Judy Beeler (FDA -CBER)
Yodit Belew (FDA -CDER)
Prabha Viswanathan (FDA -CDER)
Sonnie Kim (NIH -NIAID)
April Killikelly (Public Health Agency of Canada)
Winnie Siu (Public Health Agency of Canada)
Valerie Marshall (OIDP/OASH)
Jessica Lee (CMS/CMCS)
Terry Dalle -Tezze (HRSA)
Lucia Lee (FDA -CBER)
Robin Wisch (FDA -CBER)
13Work group members (CDC)
Amber Winn
Chris Taylor
Tami Skoff
Angie Campbell
Michael Melgar
Amanda Payne
Nicole Dowling
Noelle Molinari
Claire Midgley
Fiona HaversPragna Patel
Andrea Sharma
Amadea Britton
Ruth Link -Gelles
Danielle Moulia
Megan Wallace
Monica Godfrey
Karen Broder
Naomi Tepper
Heidi MolineCDC ACIP Staff
Melinda Wharton
Stephanie Thomas
Jessica MacNeilHannah Rosenblum
Derrell Powers
Raigan Wheeler
Sally Ezra
Elizabeth Greene
Manisha Patel
Tom Shimabukuro
Demorah Hayes
Latifah BoyceCDC
Katherine Fleming -Dutra (co -lead)
Jefferson Jones (co -lead)
Meredith McMorrow
Mila Prill
Natalie Thornburg
Aron Hall
Ismael Ortega -Sanchez
Melissa Coughlin
Jamison Pike
Lauren RoperA. Patricia Wodi
Neil Murthy
Christine Olson
Anne Hause
Andrew Leidner
David Shay
Sarah Meyer
14
For more information, contact CDC
1-800 -CDC -INFO (232 -4636)
TTY:  1 -888 -232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.

Summary: 1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Maternal/Pediatric Respiratory Syncytial Virus (RSV)  Work Group Sarah S. Long, MD Chair, Maternal/Pediatric RSV Work Group ACIP General Meeting September 22, 2023…


02 Mat Peds DeSilva 508

RSVpreF Vaccine Safety
Surveillance in Pregnancy from
The Vaccine Safety Datalink
Malini DeSilva, MD, MPH
ACIP meeting
September 22, 20231

Vaccine Safety Datalink (VSD), 2023
•Collaborative project between
CDC and integrated healthcare
organizations
•Monitors safety of vaccines
used in the U.S., primarily
through real -world data of
rare and serious events
following vaccination
•Includes data on ~15.5 million
individuals across all sites
annually
•~ 115,000 annual live births
•Data is organized using a
common data model with
standardized coding systems
2
Vaccine Safety Datalink (VSD) data structure
•Distributed data model –each VSD site creates standardized data files
•Define cohort
•Vaccines
•Diagnoses & procedures from inpatient/outpatient/emergency
•Birth and death files
•Dynamic pregnancy episode file –validated algorithms for identifying
ongoing & completed pregnancies, updated weekly
•Pregnancy start, last menstrual period (LMP)
•Gestational age
•Pregnancy outcome (when available)
•Mom -baby linkage
•Ancillary drug or lab files available ad -hoc for specific studies
•Automated data files supplemented with chart review, as needed
3
4

Prenatal RSVpreF
Vaccine Background
•RSVpreF (Pfizer) effective against
severe RSV -associated LRTI in infants
•RSVpreF clinical trial data on safety in
pregnant persons
•Injection site pain most common
reactogenicity event
•Imbalance in preterm births in
vaccinated group
•Most late preterm (34 –<37
weeks)
•Most occurred >30 days after
vaccination
•Most prominent in a single
country
•GSK RSV prenatal vaccine clinical trial
halted due to imbalance in preterm
birth in vaccinated5
Goal & Challenges
Prenatal RSVpreF Vaccine Surveillance
•Goal : To evaluate the safety of RSVpreF vaccine administered
during pregnancy in the VSD’s large, real -world population
•Challenges :
•Vaccine uptake
•Healthy vaccinee bias
•Uncertain recommendations for RSVpreF use & administration
•Coadministration of COVID -19, influenza, Tdap
6
Pregnancy Outcomes
7
1sttrimester 2ndtrimester 3rdtrimester
LMP
LMP = Last menstrual periodPregnancy
Pregnancy Outcomes
8
1sttrimester 2ndtrimester 3rdtrimester
LMP 20 weeks 26 weeksNon -viablePeriviable
PretermTerm
37 weeksLive Birth
LMP = Last menstrual periodPregnancy
Pregnancy Outcomes
9
1sttrimester 2ndtrimester 3rdtrimester
LMP 20 weeks 26 weeksNon -viablePeriviable
PretermTerm
37 weeksSpontaneous Abortion Stillbirth
IUFD
Live Birth
IUFD = Intrauterine Fetal DemiseLMP = Last menstrual periodPregnancy
Pregnancy Outcomes
10
1sttrimester 2ndtrimester 3rdtrimester
LMP 20 weeks 26 weeksNon -viablePeriviable
PretermTerm
37 weeksSpontaneous Abortion Stillbirth
IUFD
Live Birth
IUFD = Intrauterine Fetal DemiseLMP = Last menstrual periodPregnancy
RSVpreF
32 weeks
Pregnancy Outcomes
11
1sttrimester 2ndtrimester 3rdtrimester
LMP 20 weeks 26 weeksNon -viablePeriviable
PretermTerm
37 weeksSpontaneous Abortion Stillbirth
IUFD
Live Birth
IUFD = Intrauterine Fetal DemiseLMP = Last menstrual periodPregnancy
RSVpreF
32 weeks
Prenatal RSVpreF Surveillance
•Bimonthly surveillance
•Use validated algorithms applied to electronic health data in
VSD to identify pregnant persons 16 –49 years at ≥20 weeks’
gestation
•Exclude pregnancies: ending in therapeutic abortion, multiple
gestation, and with insufficient information to date pregnancy
•Exposure: RSVpreF vaccination ≥28 weeks gestation
•Match 1:1, vaccinated: unvaccinated
•VSD Site & gestational age
•Create propensity scores to account for confounding using readily
available variables (e.g., age, pregnancy start date, race, ethnicity,
medical comorbidities)
12
•Acute outcomes
•Use algorithm developed for other VSD safety surveillance and
modified for pregnant population
•Diagnoses associated with outpatient, emergency department,
and hospital encounters
•Chart confirmation for selected outcomes
•Pregnancy related and birth outcomes
•Preeclampsia/eclampsia –ICD-10 codes
•Preterm birth –gestational age at birth
•Stillbirth –ICD-10 codes with chart review confirmation
13Adverse outcomes evaluated
Acute Outcomes
Outcome Risk window(s)
(days)VSD Background
rate/10,000*
Anaphylaxis 0–1 n/a
Fever 1–7 3.3
Malaise / fatigue 1–7 11.4
Skin and soft tissue or local allergic reactions 1–7 7.0
Acute disseminated encephalomyelitis 1–21, 1–42 0
Acute myocardial infarction 1–21, 1–42 0.3
Appendicitis 1–21, 1–42 0.6
Bell's Palsy 1–21, 1–42 0.8
Cerebral venous sinus thrombosis (CVST) 1–21, 1–42 0.1
Disseminated intravascular coagulation (DIC) 1–21, 1–42 0.3
Guillain -Barré syndrome 1–21, 1–42 0
Immune thrombocytopenic purpura (ITP) 1–21, 1–42 7.6
Lymphadenopathy / lymphadenitis 1–21, 1–42 4.6
14*Identified from unvaccinated pregnant persons, COVID -19 medically attended acute outcomes 1 –7 or 1 –21 day evaluation
Acute Outcomes, continued
15Outcome Risk window (d) Background
rate/10,000*
Myocarditis / pericarditis 1–21, 1–42 0
Pulmonary embolism (PE) 1–21, 1–42 0.1
Seizure 1–21, 1–42 0.8
Stevens -Johnson syndrome or toxic epidermal necrolysis 1–21, 1–42 n/a
Stroke, hemorrhagic 1–21, 1–42 0.4
Stroke, ischemic 1–21, 1–42 0.4
Thrombosis with thrombocytopenia syndrome (TTS) 1–21, 1–42 n/a
Thrombotic thrombocytopenic purpura (TTP) 1–21, 1–42 n/a
Transverse myelitis 1–21, 1–42 n/a
Trigeminal neuralgia and related disorders 1–21, 1–42 0.1
Venous thromboembolism (VTE) 1–21, 1–42 0.4
*Identified from unvaccinated pregnant persons, COVID -19 medically attended acute outcomes 1 -21 day evaluation
Pregnancy related and birth outcomes
16Outcome Risk window Pfizer phase 3
RSVpreF trial, n (%)¥
Preeclampsia and eclampsia 1-21, 1 -42 68/3682 (1.8)¥
Preterm birth (<37 w) Up to 37 weeks 126/2494 (5.1)∆
Stillbirth 1-21, 1 -42 10/3682 (0.3)¥
¥ RSVPreF Phase 3 clinical trial: Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants | NEJM
∆Preterm birth rate in high -income countries (Slide 23 Evidence to Recommendations Framework: (cdc.gov) )
Prenatal RSVpreF Surveillance Analysis
•Risk ratios with corresponding 95% CI using Poisson distribution
with robust variance using generalized estimating equation
(GEE)
•Censoring within risk windows when no longer at risk, due to
pregnancy outcome, or if an unvaccinated match is vaccinated
•Adjustments for known confounders
•If preterm births signal detected, exploration into etiology
•Sensitivity Analysis: alternative matching strategies
•Exploratory: Coadministration of Tdap and RSVpreF
17
Example timeline
18Vaccines start 2 months 1stdata pull2-month data lag
10/1/2023 11/30/2023 1/22/202442-day follow -up
3/22/2024
Repeat analyses every 60 days/2 months
Our Team
HealthPartners
•Malini DeSilva
•Elyse Kharbanda
•Jacob Haapala
•Gabriela Vazquez -Benitez
•Leslie Kuckler
•Robyn Kaiser
•Jingyi Zhu
•Sunita Thapa
•Sheryl Kane
•Nicole Trower
19Weill Cornell Medicine
•Heather Lipkind
Kaiser Northwest
•Kimberly Vesco
CDC
•Eric Weintraub
•Elizabeth QuincerOther VSD sites
•Acumen
•Denver Health
•Harvard Pilgrim
•Indiana University
•Kaiser Permanente Northwest
•Kaiser Permanente Colorado
•Kaiser Permanente Southern
California
•Kaiser Permanente Northern
California
•Kaiser Permanente Washington
•Kaiser Permanente Mid -Atlantic
States
•Marshfield Clinic
•OCHIN

Summary: RSVpreF Vaccine Safety  Surveillance in Pregnancy from  The Vaccine Safety Datalink Malini DeSilva, MD, MPH ACIP meeting September 22, 20231  Vaccine Safety Datalink (VSD), 2023 •Collaborative project between  CDC and integrated healthcare  organizations •Monitors safety of vaccines  used in the U.S., primarily  through real -world data of  rare and serious events  following vaccination •Includes data on ~15.5 million  individuals across all sites  annually •~ 115,000 annual live births •Data…


03 Mat Peds Moro 508

Centers for Disease Control and Prevention
National Center for Emerging and Zoonotic Infectious Diseases
Maternal RSV vaccine safety monitoring in the
Vaccine Adverse Event Reporting System (VAERS)
and V -safe
Pedro L. Moro, MD, MPH
Immunization Safety Office
Centers for Disease Control and Prevention (CDC)
Advisory Committee for Immunization Practices
September 22, 2023
2Co-managed by
CDC and FDA
Vaccine Adverse Event Reporting System (VAERS)
Vaccine Adverse
Event Reporting
System
+
http://vaers.hhs.gov
3VAERS
Strengths
▪National data
▪Accepts reports from anyone
▪Rapidly detects safety signals
▪Can detect rare adverse events
▪Data available to publicLimitations
▪Reporting bias
▪Inconsistent data quality and completeness
▪Lack of unvaccinated comparison group
▪Generally cannot assess causality
•VAERS accepts all reports from all reporters without making judgments on
causality or judging clinical seriousness of the event
•As a hypothesis generating system, VAERS identifies potential vaccine safety
concerns that can be studied in more robust data systems
4Approaches to analyzing VAERS data
▪For more than a decade VAERS has been used as part of vaccine safety
surveillance for vaccines used in pregnancy (e.g., influenza, Tdap, COVID -19)
•Descriptive analysis
oClinical review of individual reports
oAggregate descriptions of automated data (e.g., counts of reported adverse events)
oCalculation of reporting rates for pregnancy outcomes (if doses of RSV vaccine
administered in pregnancy or vaccination coverage data available are available)
•Statistical analysis
oHistorical approaches have included data mining; under discussion
*Reported adverse events are coded using Medical Dictionary for Regulatory Activities terms ( https://www.meddra.org/ )
5Search for RSV pregnancy reports and clinical review
▪Search of reports:
•Specific Medical Dictionary for Regulatory Activities (MedDRA) codes: exposure during
pregnancy, drug exposure during pregnancy, maternal exposure during pregnancy
•Affirmative answer on Question 8 in VAERS form (pregnancy status)
•String search of text fields (symptoms, pre -existing illness, medical history) for ‘ preg ’
▪Medical records requested for ALL pregnancy reports
▪Clinicians review reports to confirm they are pregnancy reports and
categorize the main adverse event/s of interest

VAERS surveillance of adverse events of special interest (AESI)
after RSV vaccination
▪Primary AESIs
•Selected for historical, theoretical, or observed safety concerns (i.e., in clinical trials)
•VAERS will obtain medical records for all reports (serious1and non -serious)
•CDC will review records and abstract clinically important information
•AESIs may be added to or removed from the list as appropriate
▪Secondary AESIs
•Monitored via periodic (e.g., weekly) automated data tables
•Can be added to primary AESI list if safety concerns identified
1Based on the Code of Federal Regulations if one of the following is reported: death, life -threatening illness, hospitalization o r prolongation of
hospitalization , permanent disability, congenital anomaly or birth defect
6
Adverse events of special interest (AESI) after RSV vaccines
Primary AESIs
▪Outcomes of general interest
• Death
▪Neurologic/neuroinflammatory conditions
• Guillain -Barre Syndrome (GBS), including Miller
Fisher variant
• Acute disseminated encephalomyelitis (ADEM)
• Transverse myelitis (TM)
• Chronic inflammatory demyelinating
polyneuropathy (CIDP)
▪Allergic reactions
• Anaphylaxis
▪Cardiac conditions
•Atrial fibrillation
•Other supraventricular tachycardias (SVT)Secondary AESI s
▪Neurologic/neuroinflammatory conditions
• Optic neuritis
• Multiple sclerosis
• Bell’s palsy
• Encephalitis/Encephalomyelitis
• Meningitis/Meningoencephalitis
• Myelitis
▪ Other conditions
• Vaccination errors
• AEs following simultaneous administration with
COVID -19, inactivated influenza, or other adult
vaccinesWill be monitored in VAERS for all RSV vaccines, including for reports among pregnant persons
8Pregnancy -specific outcomes to be monitored in
VAERS and abstracted after maternal RSV vaccine
▪Pregnancy reports after maternal RSV vaccine
•Premature/preterm birth
•Stillbirth
•Spontaneous abortion
•Gestational diabetes
•Preeclampsia/eclampsia/gestational hypertension
•Birth defects
•Maternal and infant deaths
•Other selected adverse infant outcomes/AEs
9▪New version of V -safe developed starting Summer 2023
•Leverages existing CDC IT infrastructure
•Includes email and text messaging options
•First use for RSV vaccines received by persons aged 60 and older
•Use for maternal RSV vaccines planned for later this fall
▪V-safe objectives:
1. Characterize local and systemic reactogenicity during days 0 -7 after vaccination
2. Characterize health impacts during a 6 -week post -vaccination follow -up period
3. Identify participants who report medically attended events after vaccination and
encourage completion of a VAERS report

For more information, contact CDC
1-800-CDC-INFO (232 -4636)
TTY:  1 -888-232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the
official position of the Centers for Disease Control and Prevention.Thank you

Summary: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases Maternal RSV vaccine safety monitoring in the  Vaccine Adverse Event Reporting System (VAERS)  and V -safe Pedro L. Moro, MD, MPH Immunization Safety Office Centers for Disease Control and Prevention (CDC) Advisory Committee for Immunization Practices  September 22, 2023 2Co-managed by CDC and FDA Vaccine Adverse Event Reporting System (VAERS) Vaccine Adverse Event Reporting  System +…


04 Mat Peds Hutton 508

Economic Analysis of RSVpreF
Maternal Vaccination
David W. Hutton, PhD, MS
Professor, Health Management and Policy, School of Public Health
Professor of Global Public Health, School of Public Health
Professor, Industrial and Operations Engineering, College of Engineering
University of MichiganSeptember 22, 2023

Research team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Kerra Mercon , MSCDC
•Jefferson Jones, MD, MPH, FAAP
•Mila Prill, MSPH
•Meredith McMorrow, MD, MPH, FAAP
•Jamison Pike, PhD
•Katherine Fleming -Dutra, MD, FAAP
•Ismael Ortega -Sanchez, PhD
•Fiona Havers, MD
•Betsy Gunnels, MSPH
•Andrew Leidner , PhD
2
Conflicts of interest statements
•Authors have no known conflict of interests.
3
•Additional vaccine efficacy scenario
•Additional timing scenarios
•Months of year to administer
•32 Τ07-36 Τ67weeks gestation
•Updated cost/doseUpdates Since June 21 Presentation
Economic Analysis of RSV Vaccination in Older Adults, June 21, 2023
0%20%40%60%80%100%
0 3 6 9 12Efficacy
Month
Against medically-attended RSV-associated LRTI Against hospitalization
5Methods: RSVpreF efficacy
average 6 -month efficacy = efficacy against
hospitalization or medically -attended RSV -
associated LRTI
Zero efficacy
Source: Kampmann et al 2023
LRTI= Lower respiratory tract infection
0%20%40%60%80%100%
0 3 6 9 12Efficacy
Month
Against medically-attended RSV-associated LRTI Against hospitalization
6Methods: RSVpreF efficacy
alternate flat scenario
Zero efficacy
Source: Kampmann et al 2023
LRTI= Lower respiratory tract infectionaverage 6 -month efficacy = efficacy against
hospitalization or medically -attended RSV -
associated LRTI
0%20%40%60%80%100%
0 3 6 9 12Efficacy
Month
severe MA RSV LRTI MA RSV LRTI
7Methods: RSVpreF efficacy
Optimistic scenario: Severe Efficacy with VE to 9 months
6-month efficacy against
Severe MA RSV LRTI
Zero efficacy
at 9 months6-month efficacy against
MA RSV LRTI
MA: Medically -attended, LRTI: Lower Respiratory Tract Infection
Methods: Provision of RSVpreF
8•Base case:
•Year round
•Scenarios
•Individual Months
•Ranges of Months
•April -February
•May -February
•June -February
•August -January
•September -January
•September -December
•Mother vaccinated
•During 32 Τ07-36 Τ67weeks gestation, evenly distributed
•Birth
•Must be >2 weeks after vaccination for protective efficacy to pass to infant,
based on historical gestational age
9Methods: Provision of RSVpreF
Methods: Provision of RSVpreF
10In Time= >2 weeks prior to delivery100 Pregnant persons50
No intention
50
Intend to Vaccinate
45
Vaccinated
in time2
Birth before vaccinationUptake
Timing48
Vaccinated3
Vaccinated < 2 weeks
before delivery
Results: Base case
11•Base case:
•Population of annual US births ( 3.66 million )
•50% intended uptake in the RSVpreF group
•First RSV season
•$295/dose
•RSVpreF only impacts lower respiratory tract infections
Results: Number Needed to Vaccinate
12Cohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group40 115 242 1,100
45 367
 - 200 400 600 800 1,000 1,200
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Vaccinate to avoid
RSVPreF
Results: Costs
13Base costs of RSVpreF : $295/dose, both natural history and RSVPreF involve palivizumab for high -risk childrenCohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group$0$500$1,000$1,500$2,000$2,500
Natural
HistoryRSVPreF Natural
HistoryRSVPreF Natural
HistoryRSVPreF Natural
HistoryRSVPreF Natural
HistoryRSVPreF Natural
HistoryRSVPreF
Intervention Outpatient ED Inpatient Deaths TotalTotal Costs in Cohort
Millions
Medical Productivity
Results: Cost per Event Averted
14Base costs of RSVpreF : $295/dose$11,337 $32,652 $68,423 $311,013
$12,671 $103,671
 $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000
Outpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted
RSVPreF
Results: Cost -Effectiveness
15Base costs of RSVpreF : $295/dose
QALY= quality -adjusted life -year; ICER= incremental cost -effectiveness ratioCohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group, ICER is not affected by uptakeOverallCosts ($) QALYs lostICER ($/QALY)
Vs. NH
Natural History 1,585,172,002 18,151
RSVpreF 2,103,215,047 16,857 400,304
$0 $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000 $800,000
Probability of Prematurity
RSV QALYS Lost
RSVpreF vaccine cost/dose
Disease-specific inpatient costs (per inpatient case)
Vaccination Efficacy, Hospitalized RSV LRTI through 180 days
Vaccination Efficacy, RSV MA-LRTI through 180 days
Proportion of RSV infections with an LRTI diagnosis Outpatient Age 0-5 months
Proportion of RSV infections with an LRTI diagnosis ED Visits Age 0-5 months
Proportion of RSV infections with an LRTI diagnosis Hospitalizations Age 0-5 months
RSV mortality per hospitalization Age 0-5 monthsIncremental Cost -Effectiveness Ratio
Low HighSensitivity: Tornado RSVpreF
16Base cost of RSVpreF : $295/dose
MA= Medically -attended
LRTI= Lower respiratory tract infection
QALY= Quality adjusted life year$1.3 million
Methods: RSVpreF efficacy
“flat efficacy” scenario
17Overall Costs ($) QALYs lost ICER ($/QALY)
Natural History 1,585,172,002 18,151
RSVpreF 2,094,993,469 16,757 365,669
Slightly lower costs with
RSVpreF , slightly fewer
QALYs lost, slightly lower
ICER
ICER: Incremental cost -effectiveness ratio
LRTI= Lower respiratory tract infection

Sensitivity Analysis: More Optimistic Efficacy
18Base costs of RSVpreF : $295/dose
QALY= quality -adjusted life -year; ICER= incremental cost -effectiveness ratioCohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group, ICER is not affected by uptakeOverallCosts ($) QALYs lostICER ($/QALY)
Vs. NH
Natural History 1,585,172,002 18,151
RSVpreF 2,056,423,553 16,504 286,179
Higher and longer efficacy
MA: Medically -attended, LRTI: Lower Respiratory Tract Infection
19Sensitivity: Varying Efficacy, Hospitalization Cost, and
Mortality
Base$0$100,000$200,000$300,000$400,000$500,000
$0 $10,000 $20,000 $30,000 $40,000 $50,000 $60,000ICER
Hospitalization Cost
0.1% Mortality, Base Efficacy 0.1% Mortality, Optimistic Efficacy
1.0% Mortality, Base Efficacy 1.0% Mortality, Optimistic Efficacy
 $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000 $800,000
$0 $50 $100 $150 $200 $250 $300 $350 $400 $450 $500ICER
Cost per dose of RSVpreFSensitivity: Cost RSVpreF
20Base Case
Results: RSVpreF timing scenarios
21•Scenarios
•Base: vaccine given year -round
•By Month
•During April -February
•During May -February
•During June -February
•During August -January
•During September -January
•During September -December
Results: RSVpreF timing scenarios
$351,238 $333,255
$181,649
$115,445 $111,248 $174,344
 $- $100,000 $200,000 $300,000 $400,000 $500,000
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov DecICER ($.QALY)ICER: RSVpreF vs. Natural History
22Month of administration
Results: RSVpreF timing scenarios
$400,304
$363,344
$322,594
$282,498
$186,256 $167,280 $141,806
 $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000
Base Apr-Feb May-Feb Jun-Feb Aug-Jan Sep-Jan Sep-DecICER ($.QALY)ICER: RSVpreF vs. Natural History
23
Limitations
•Model Structure
•No risk groups
•No dynamic transmission. No impact of the vaccine on transmission and
indirect effects
•Uncertain inputs
•RSVpreF cost
•QALYs lost
•Upper respiratory tract infections
•Prematurity
•Assumption: no infants will be receiving nirsevimab
24
Summary
•RSVpreF may improve RSV outcomes, but will also increase costs
•RSVpreF has the potential to be cost -effective
•Results sensitive to:
•Rate of prematurity
•Cost per dose (~65,000 –68$/QALY)
•Hospitalization Costs (Cost -saving –440,000 $/QALY)
•Efficacy (~280,000 –680,000 $/QALY)
•QALYs lost (~100,000 –800,000 $/QALY)
•Month of Administration (~110,000 –Millions $/QALY)
25QALY: Quality -Adjusted Life -Year
Economics of combined use of Pfizer
maternal RSVpreF vaccine and
nirsevimab
David W. Hutton, PhD, MS
Professor, Health Management and Policy, School of Public Health
Professor of Global Public Health, School of Public Health
Professor, Industrial and Operations Engineering, College of Engineering
University of MichiganSeptember 22, 2023

•On August 3, 2023, the Advisory Committee on Immunization
Practices (ACIP) recommended use of nirsevimab
•How should we think about combinations of RSVpreF and
nirsevimab ?
•If we know RSVpreF has been administered in time, how cost -effective is it to
provide nirsevimab ?
•If we know the infant will receive nirsevimab , how cost -effective is it to
provide RSVpreF ?Methods: Study questions
•RSVpreF will be administered in weeks 32 -36
•Because of this, we are assuming the infant is full -term, and therefore, there is no need for
palivizumab for any newborns considered in this analysis
•Consideration of higher -risk populations (but assuming they are not premature)
•New timing of RSVpreF administrationUpdates since June
Methods: Intervention effectiveness
•NO evidence of efficacy on the combined use of these products
•Assumption:
•Efficacy equal to the highest of nirsevimab or RSVpreF :
•Efficacy would not be higher than from the most effective product
29
0%20%40%60%80%100%
0 2 4 6 8 10 12 14Hospitalization Efficacy
Months since birth
RSVPreF Both NirsevimabMethods: Intervention effectiveness
30
Additional benefit of adding nirsevimab
* Assuming administration of nirsevimab at birth

0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12Hospitalization Efficacy
Month
Both RSVpreF OnlyMethods: Intervention effectiveness
Example: Off -peak (Aug) birth
Additional benefit of adding nirsevimab
Note: Peak infections are typically Dec -Feb
 31
Incremental benefit of adding nirsevimab on top of
RSVpreF
32•For infants of persons vaccinated with RSVpreF during pregnancy at
least 2 weeks prior to delivery
Results: Incremental benefit of adding nirsevimab
on top of RSVpreF : Higher Risk
•Higher -Risk
•Increased multiplier on
•risk of hospitalization
•No change in
•Outpatient incidence
•ED incidence
•Cost/outcome
•QALYs/outcome
33
Results: Incremental benefit of adding nirsevimab
on top of RSVpreF : By Month and Risk
 $- $200,000 $400,000 $600,000 $800,000 $1,000,000 $1,200,000 $1,400,000 $1,600,000 $1,800,000ICER
1x 2x 3x 6x 10x
34Nirsevimab given in Oct -Mar
ICER= Incremental cost effectiveness ratio ($/QALY)
If the 10x bars are “missing”, providing nirsevimab is cost -saving.Birth Month
Risk LevelNirsevimab given at birth Nirsevimab given Oct/Nov
Results: Incremental benefit of adding nirsevimab
on top of RSVpreF : By Month and Risk
 $- $50,000 $100,000 $150,000 $200,000 $250,000ICER
3x 6x 10x
35Nirsevimab given in Oct -Mar
ICER= Incremental cost effectiveness ratio ($/QALY)
If the 10x bars are “missing”, providing nirsevimab is cost -saving.Birth Month
Risk LevelNirsevimab given at birth Nirsevimab given Oct/Nov
Results: Adding nirsevimab to allinfants born year -
round to vaccinated mothers
 - 200 400 600 800 1,000 1,200 1,400
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber Needed to Immunize to
Avoid One…
1x 2x 3x 6x 10x
36Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April through
September to mothers who received RSVpreF at least 2 weeks prior to delivery
Results: Adding nirsevimab to allinfants born year -
round to vaccinated mothers
37Notes: Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April through September to
mothers who received RSVpreF at least 2 weeks prior to delivery
ICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -year$413,035
$282,083
$192,782
$40,256
 $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000
ICERICER
1x 2x 3x 6x 10xCost -Saving
Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF at least 2 weeks prior to deliveryResults: Adding nirsevimab at the start of the
season only for infants born Apr-Sept
 - 200 400 600 800 1,000 1,200
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber Needed to Immunize to
Avoid One…
1x 2x 3x 6x 10x
38
Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF at least 2 weeks prior to delivery
ICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -yearResults: Adding nirsevimab at the start of the
season only for infants born Apr-Sept
39$305,182
$203,194
$131,505
$4,830
 $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000ICER
1x 2x 3x 6x 10xCost -Saving
Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF at least 2 weeks prior to deliveryResults: Adding nirsevimab during the season for
infants born Oct-Mar
 - 200 400 600 800 1,000 1,200 1,400 1,600
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber Needed to Immunize to
Avoid One…
1x 2x 3x 6x 10x
40
Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF at least 2 weeks prior to delivery
ICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -yearResults: Adding nirsevimab during the season for
infants born Oct-Mar
41$606,362
$416,695
$293,926
$95,537
 $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000ICER
1x 2x 3x 6x 10xCost -Saving
•Additional benefit beyond RSVpreF protection
•ICERs are high, but could be lower for higher -risk populations,
particularly if born off -peakSummary: Incremental benefit of
adding nirsevimab on top of RSVpreF
42
Incremental benefit of adding RSVpreF on top of
nirsevimab
•If you know the infant will be receiving nirsevimab
43
Results: Incremental benefit of adding RSVpreF on
top of nirsevimab
$2.4 $6.0 $9.4
$5.0
$3.6
 $- $1.0 $2.0 $3.0 $4.0 $5.0 $6.0 $7.0 $8.0 $9.0 $10.0ICER (Millions)
44Birth Month
ICER= Incremental cost effectiveness ratio
Summary: Incremental benefit of adding RSVpreF
on top of nirsevimab
•Very marginal additional benefit beyond nirsevimab protection
•ICERs are extremely high
45
Overall summary: Combinations
•Limitation:
•No efficacy data for combination of products
•Nirsevimab may add additional protection on top of RSVpreF ,
particularly for higher -risk infants.
•Adding RSVpreF on top of nirsevimab adds marginal effectiveness at
very high cost in the general population
46
Thank You
•Please send comments to:
•dwhutton@umich.edu
47
Appendix to Economics of Pfizer maternal
RSVpreF vaccine
48
Research team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Kerra Mercon , MSCDC
•Jefferson Jones, MD, MPH, FAAP
•Mila Prill, MSPH
•Meredith McMorrow, MD, MPH, FAAP
•Jamison Pike, PhD
•Katherine Fleming -Dutra, MD, FAAP
•Ismael Ortega -Sanchez, PhD
•Fiona Havers, MD
•Betsy Gunnels, MSPH
•Andrew Leidner , PhD
49
Conflicts of interest statements
•Authors have no known conflict of interests.
50
Methods: Study question
•Determine the cost -effectiveness of RSVpreF by:
•Evaluating the population impact in terms of
•annual resource utilization
•total cases
•total costs
•deaths
•quality -adjusted life -years (QALYs)
•Comparing the incremental cost -effectiveness ratio (ICER) of RSVpreF to natural history/no
vaccine.
•Running scenario analyses outcomes that explore key areas of uncertainty.
•Perspective: Societal
51
Methods: Intervention(s)
•Target population: US pregnant persons
•Interventions:
1.No vaccination (Natural history)
2.RSVpreF against RSV illness
•Timeframe: 1 year (1 RSV season)
•Analytic horizon: infant’s lifetime
•Discount rate: 3%
52
Methods: Decision tree model
53Natural
History
RSVpreFInfection Hospitalization
ED
None of the aboveOutpatientAlive
DeadInfection
Adverse
EventsPrematurity
Injection site reaction
None of the aboveSerious adverse eventInfection Infection
Methods: Epidemiology
Hospitalization
54Base Case Range Source
Respiratory syncytial virus (RSV)
incidence, per 100,000 See Above See AboveCDC NVSN,
December 2016 to September 2020
Proportion with LRTI
Age 0 -5 months 1.0 0.5-1.0 Rainisch, 2020
Age 6 -11 months 1.0 0.5-1.0 Rainisch , 2020
CDC New Vaccine Surveillance Network (NVSN) hospitalization rates for children under 2 years of age from December 2016 to Sep tember 2020 - 1,000 2,000 3,000 4,000
0 2 4 6 8 10 12 14 16 18 20 22Hospitalization rate
per 100,000
children
Age in months
Methods: Epidemiology
ED and Outpatient
55Respiratory syncytial virus (RSV)
incidence, per 100,000 Base Case Range Source
Emergency Department
Age 0 -5 months 7,500 5,500 –7,500 Lively 2019 (base case and range), Hall
2009 (range)
Age 6 -11 months 5,800 5,700 –5,800 Lively 2019 (base case and range), Hall
2009 (range)
Age 12 -23 months 3,200 3,200 –5,300 Hall 2009 (base case and range), Lively
2019 (range)
Proportion with LRTI
Age 0 -5 months 0.65 0.25 -1.0 Rainisch , 2020
Age 6 -11 months 0.5 0.25 -1.0 Rainisch , 2020
Outpatient
Age 0 -5 months21,60013,200 –21,600 Lively 2019 (base case and range), Hall
2009 (range)
Age 6 -11 months24,60017,700 –24,600 Lively 2019 (base case and range), Hall
2009 (range)
Age 12 -23 months18,4406,600 –29,620 Jackson 2021 (base case and range),
Hall 2009 (range)
Proportion with LRTI
Age 0 -5 months 0.65 0.25 -1.0 Rainisch , 2020
Age 6 -11 months 0.3 0.1-1.0 Rainisch , 2020
LRTI= Lower respiratory tract infection
Methods: Epidemiology
Mortality
56Base
CaseRange Source
RSV mortality per
hospitalization
Age 0 -5 months 0.10%0.04 -0.20%Hansen 2022,
Doucette 2016
Age 6 -11 months 0.10%0.04 -0.20%Hansen 2022,
Doucette 2016
Age 12 -23 months 0.3% 0.28% -0.34% Gupta 2016
Seasonality
570%5%10%15%20%25%30%
Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections
Source: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)
Methods: Efficacy
58Variable Base case
valueRange for
sensitivity
analysisSource
RSVpreF
Initial efficacy (months 0 -5)
against medically -attended
RSV-associated LRTI 51.3% 29.4% -66.8%Kampmann
et al, 2023
Initial efficacy (months 0 -5)
against hospitalized RSV -
associated LRTI 56.8% 10.1% -80.7%Kampmann
et al, 2023
Efficacy months 6 -12 0
Assumed 0% efficacy against upper respiratory tract infections
LRTI= Lower respiratory tract infection
Methods: Medical Costs
Variable Value Range Source
Disease -specific
hospitalization costs (per
hospitalization)
Age 0 -11 months $11,487 4,804 -86,646
Bowser 2022Age 12 -23 months $11,469 4,804 -86,646
Disease -specific ED costs
(per ED visit)$563 544 -581 Bowser 2022
Disease -specific
outpatient costs (per
outpatient visit)$82 46 -118 Bowser 2022
59•Bowser, 2022 is a systematic review using studies from 2014 -2021
•Funded by Sanofi
•All numbers updated to 2022 dollars using GDP Deflator
Methods: Productivity costs
Variable Value Range Source
Productivity burden of RSV
disease (caregiver losses)
Days of lost productivity
Outpatient* 2.5 0-5Fragaszy, 2018; Petrie, 2016;
Van Wormer, 2017
ED* 2.5 0-5Fragaszy, 2018; Petrie, 2016;
Van Wormer, 2017
Hospitalization^ 7.4 0-14
Lifetime productivity for
those <1 year old (lost from
death)1,795,936 1,346,951 -
2,244,919Grosse, 2019
60*Productivity for outpatient and ED based on adult influenza
^Hospitalization productivity loss = length of hospitalization + 2 days
Methods: Intervention cost
Variable Value Range Source
Immunization -related costs
RSVpreF , per dose $295 50 –500Assumption: Manufacturer
costs for adult vaccine
RSVpreF administration $16.96 15 -22 Medicare: HCPCS 90460
61Both assume no additional visits, but do include costs of administration
Methods: Adverse event costs
Variable Value Range Source
RSVpreF Maternal Adverse
Events
Rate of injection site reaction 0.41 0.38 –0.44 Pfizer Phase 3 Trial
Probability of healthcare
visit, given injection site
reaction0.02 0.015 –0.025 Curran, 2020
Cost of outpatient visit $367.76 23.15 –1,758 (Deluca, 2023)
Recipient time, physician
office for injection site
reaction (hours)2 1 -3 Assumption
Hypothetical serious
adverse event0.000001 0 -0.0002Base: Prosser, 2006
High: 95% CI Phase 3 data for
RSV adult vaccines
62
63Kampmann B, Madhi SA, Munjal I, Simões EA, Pahud BA, Llapur C, Baker J, Pérez Marc G, Radley D, Shittu E, Glanternik J.
Bivalent prefusion F vaccine in pregnancy to prevent RSV illness in infants. New England Journal of Medicine. 2023 Apr 5.Methods: Prematurity?
1% Difference?

Methods: Prematurity scenario
Variable Value Range Source
RSVpreF infant adverse
events
Higher Rate of Prematurity 0% 0-2% Pfizer Phase 3 Trial
64 * All costs updated to 2022 using GDP DeflatorOutcomes, per prematurity
Lifetime cost of late
prematurity
Medical $ 23,241 $11,621 –
$46,482 Waitzman , Jalali, Grosse, 2021
Productivity $ 11,447 $5,724 –
$22,894 Waitzman , Jalali, Grosse, 2021
QALYs lost from late
prematurity0.03 0 –1.2Werner, Hauspurg , Rouse, 2015
Petrini et al, 2008, Hirvonen et al, 2014, Crump
et al, 2021, Darcy -Mahoney et al, 2016, Carroll
et al, 2009, Payakachat et al, 2014
Methods: RSV
health -related quality of life
65LRTI quality -adjusted life DAYS lost Base Lower (Regnier) Upper (JIVE)
Outpatient: Child 3.1 1.8 16.6
Outpatient: Caregiver 1.5 0 9.1
ED: Child 4.9 2.9 16.6
ED: Caregiver 2.5 0 9.1
Hospitalized: Child 6.2 3.7 26.5
Hospitalized: Caregiver 2.4 0 13.6Measured in
Days Lost
Most
Likely
Methods: Epidemiological model
SeasonalityIncidence
•Outpatient
•ED
•Hospitalizations
Nirsevimab
Waning
ProtectionHealth Effects
• Outpatient
• ED
• Hospitalizations
• Deaths
Economic Effects
• Intervention
• Disease
• Societal
• QALYs
• ICERInterventionsEpidemiology
Timing
Cost Burden/
•Outpatient
•ED
•HospitalizationsHealth Economics
Health Burden/
•Outpatient
•ED
•Hospitalizations
66
Methods: Inputs
•Incidence
•Raw reported incidence may be underreported because of imperfect PCR
sensitivity, so we consider an additional scenario in sensitivity analysis:
•based on CDC Unpublished re -analysis of raw data from Zhang et al study which found
decreased RSV PCR sensitivity in light of paired serology testing (adjustment factor:
87.6%).
67
Health -Related Quality -of-Life
•Sources
•Glaser (2022)
•Estimate based on comparison of utility losses between premature children who had RSV vs.
premature children without RSV and their caregivers
•Used as base case for hospitalization for children and their caregivers
•Regnier (2013)
•Estimate QALY losses for hospitalization, ED visits, and outpatient visits for children with
pertussis
•Use relative QALYs between hospitalization, ED, and outpatient to estimate base losses for ED
and outpatient in base case
•JIVE RSV Utilities Survey (2021)
•Estimates QALY losses for hospitalization and outpatient visits for child and caregiver
•Estimates may be impacted by COVID -related concerns about respiratory viruses
•Inform upper bound of range
68
69Timing of those who received vaccination during pregnancy
RSVpreF is assumed to start earlier at week 24 (vs. week 27)Methods: Provision of RSVpreF
00.050.10.150.20.25
1 3 5 7 911 13 15 17 19 21 23 25 27 29 31 33 35 37 39Fraction Vaccinated (given receipt
of vaccine)
Gestational Age
Reported Tdap Modeled RSVpreF vaccination timing
700.0%5.0%10.0%15.0%20.0%25.0%30.0%35.0%40.0%45.0%
0 10 20 30 40 50
Gestational Age (Week)
Source: NCHS from 2019 and 2021Methods: Birth Timing
Validation
231
66
8225
65
13
050100150200250
Outpatient Clinic
VisitsED Visits HospitalizationsRates of Medically -Attended RSV
(per 1000 births)
Rainisch et al, Vaccine, 2020 JIVE model
71
Methods: Maternal Adverse Event Health Effects
Variable Value Range Source
Adult Quality -Adjusted Life -
Years lost due to adverse events
Injection Site Reaction 0 Assumed
Serious Adverse Event 0.141 0.092 -0.199 Prosser, 2006
72
Results: Health outcomes
73Cohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group
URTI= upper respiratory tract infection; LRTI= lower respiratory tract infection - 100,000 200,000 300,000 400,000 500,000 600,000 700,000 800,000 900,000
Natural
HistoryRSVpreF Natural
HistoryRSVpreF Natural
HistoryRSVpreF
Outpatient Emergency Department InpatientNumber of Events in Cohort
URTI LRTI
Results: Events Averted
74Cohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group45,693
15,866
7,571
1,66640,884
4,997
05,00010,00015,00020,00025,00030,00035,00040,00045,00050,000
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per Year
RSVPreF
Results: QALYs Lost
75Adverse
EventsOutpatient ED Inpatient Deaths Total Grand
Child Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total
Natural
History 7,153 3,580 3,290 1,645 807 320 1,356 12,606 5,545 18,151
RSVpreF 0.2495 6,766 3,387 3,075 1,538 679 269 1,141 11,663 5,194 16,857
Cohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group
QALY= quality -adjusted life -year
76Sensitivity: Hospitalization Mortality
Base$0$50,000$100,000$150,000$200,000$250,000$300,000$350,000$400,000$450,000$500,000
0.00% 0.20% 0.40% 0.60% 0.80% 1.00% 1.20%ICER
Hospitalized Mortality
Scenario: Prematurity
77Base Case
 $- $200,000 $400,000 $600,000 $800,000 $1,000,000 $1,200,000 $1,400,000 $1,600,000
0.0% 0.5% 1.0% 1.5% 2.0%ICER
Excess Prematurity
Scenario: Upper Respiratory Tract Infection Effect
78RSVpreF is assumed to have 37.9% efficacy for upper respiratory tract infections based on overall respiratory tract
efficacy from phase 3 trial ( Kampmann , 2023)
ICER= incremental cost effectiveness ratio; QALY= Quality adjusted life year$279,490/QALY
 $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000
$0 $50 $100 $150 $200 $250 $300 $350 $400 $450 $500ICER
Total Cost of RSVpreF
Appendix to Economics of combined use of Pfizer
maternal RSVpreF vaccine and nirsevimab
79
Methods: Study questions
•Determine the cost -effectiveness of:
•Nirsevimab in children born to mothers who received RSVpreF at least 2 weeks prior to
delivery
•RSVpreF for pregnant persons who will give nirsevimab to their newborns
•Single individual
•Evaluate by month of year
•Perspective: Societal
•Timeframe: 1 year (1 RSV season)
•Analytic horizon: infant’s lifetime
•Discount rate: 3%
80
810.0%5.0%10.0%15.0%20.0%25.0%30.0%
Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections
Source: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)Reminder: Seasonality
Methods: Intervention effectiveness
82* Assuming administration of nirsevimab at birth0%20%40%60%80%100%
0 2 4 6 8 10 12 14Hospitalization Efficacy
Months since birth
RSVPreF Both Nirsevimab
0%20%40%60%80%100%
0 2 4 6 8 10 12 14Hospitalization Efficacy
Months since birth
RSVPreF Both NirsevimabMethods: Intervention effectiveness
83
Additional benefit of adding RSVpreF
* Assuming administration of nirsevimab at birth
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12Hospitalization Efficacy
Month
Both Nirsevimab OnlyMethods: Intervention effectiveness
example: Off -peak (Aug) birth
Additional benefit of adding RSVpreF
84

Results: Adding nirsevimab to allinfants born to
vaccinated mothers
0.00000.05000.10000.15000.20000.2500
Outpatient ED Inpatient ICU Inpatient Day ICU DayAdditional Events Averted Per
Infant Given Nirsevimab
1x 2x 3x 6x 10x
85Nirsevimab given at birth for infants born October -March, and in October/November for infants born in April through
September
Results: Adding nirsevimab at the start of the
season only for infants born Apr-Sept
0.00000.05000.10000.15000.20000.25000.3000
Outpatient ED Inpatient ICU Inpatient Day ICU DayAdditional Events Averted Per
Infant Given Nirsevimab
1x 2x 3x 6x 10x
86Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF
Results: Adding nirsevimab during the season for
infants born Oct-Mar
0.00000.05000.10000.15000.2000
Outpatient ED Inpatient ICU Inpatient Day ICU DayAdditional Events Averted Per
Infant Given Nirsevimab
1x 2x 3x 6x 10x
87Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF

Summary: Economic Analysis of RSVpreF Maternal Vaccination David W. Hutton, PhD, MS Professor, Health Management and Policy, School of Public Health Professor of Global Public Health, School of Public Health Professor, Industrial and Operations Engineering, College of Engineering University of MichiganSeptember 22, 2023  Research team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Kerra Mercon , MSCDC •Jefferson Jones, MD, MPH, FAAP •Mila Prill, MSPH •Meredith McMorrow,…


05 Mat Peds Ortega Sanchez 508

Economics of Preventing Respiratory Syncytial
Virus Disease among US Infants by Maternal
Vaccination Prior to Birth
A SUMMARY REPORT COMPARING MODELS FROM:
Pfizer AND University of Michigan and CDC
Ismael R. Ortega -Sanchez, PhD
NCIRD/CDC
ACIP Meeting, September 22, 2023
1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of
the Centers for Disease Control and Prevention.
National Center for Immunization & Respiratory Diseases
Conflict of interest
•Pfizer model : Amy Law et al., [complete authors list and affiliations, upon
request ]
•Pfizer manufactures RSVpreF vaccine
•Policy Analysis Inc. (Boston, MA, US) was funded by Pfizer
•UM-CDC model : David W Hutton et al. from University of Michigan,
Ismael R Ortega -Sanchez et al. from CDC [complete authors list and affiliations,
upon request ]
•All authors: No conflicts of interest
2
Economic analysis
Policy question: Should Pfizer RSVpreF vaccine be recommended for pregnant mothers to be given
during 32 through 36 weeks gestation to prevent RSV lower respiratory tract infection in infants?
Question : Is vaccinating pregnant mothers prior to birth to protect infants against RSV disease cost-
effective ?
Comparator Intervention
Base -case scenario: What is the incremental cost-effectiveness of vaccinating pregnant mothers 32 -36wGA and
≥2 weeks prior to birth with RSVPreF vaccine relative to “No vaccination”?
3Unvaccinated
Mothers +
Standard of care (SoC)
for InfantsVaccination of
pregnant mothers
prior to birth
Standard of Care (SoC) = Palivizumab only for infants eligible as per AAP recommendations, and no immunization for all other pr e-term and full term infants
Focus on key features for model comparison
•Modeling approach
•Targeted population(s)
•Perspective (healthcare vs. societal)
•Intervention strategies and comparators
•Inputs for RSV disease burden, vaccine efficacy, and costs
•Incidence of RSV disease, rates of outcomes
•Direct and indirect costs of RSV disease
•Intervention: efficacy, duration of protection, safety and program costs
•Assumptions
•Strong, influential assumptions
4
5Modeling design and assumptions
Pfizer UM-CDC
Static analytical decision -making models ✔ ✔
Sensitivity analyses (and probabilistic simulation) ✔(✔) ✔
Hypothetical population: All pregnant mothers, all year round ✔ ✔
Time Frame: First year after birth ✔ ✔
Analytic Horizon: One year (for temporary disability) and Life
Expectancy (for premature infant mortality)✔
✔✔
✔
Discount rate: 3% ✔ ✔
Year of economic outcomes measured: 2022 ✔ ✔
Societal perspective (and healthcare perspective) ✔(✔) ✔(✔)
6Inputs and main outcomes
Prevention of:
•RSV LRTI  ED/OC visits
•RSV LRTI hospitalizations
•RSV-associated deaths
QALYs saved
$/QALY saved
Number needed to
vaccinate (NNV) to avert an:
•RSV LRTI hospitalization
•RSV-associated deathPfizer UM-CDC
✔ ✔
✔ ✔
✔ ✔
✔ ✔
✔ ✔
✔ ✔
✔ ✔
HCRU = health care resource use, ED= Emergency department,  OC= outpatient clinic, LRTI= Lower respiratory tract infection,
QALY= quality -adjusted life year
$11 $33 $68 $311
$13 $104
 $- $50 $100 $150 $200 $250 $300 $350
Outpatient ED Inpatient ICU Inpatient
DayICU DayCost per Event Averted ( thousands )UM-CDC: Base case estimates for maternal vaccination,
Vaccination Window (VW) 32 -36wGA, vaccine cost $295/dose
7Cost per type of health outcome prevented (in thousands ) Summary outcomes Base -Case
$/QALY gained $400,304
$/RSV -associated ED/OC visit
averted $32,652 / $11,337
$/RSV -associated
LRTI hospitalization averted$68,423
$/RSV -assoc. death averted>$71.5Million
NNV to avert an RSV -associated
ED/ OC patient115 /  40
NNV to avert an RSV -associated
LRTI hospitalization242
NNV to avert an RSV -associated
death241,989
Assuming 50% uptake in vaccinated group
VW = vaccination window
wGA = weeks gestational age
LRTI= lower respiratory tract infection
OC = office clinic for outpatient care
ED = emergency department
NNV = Number needed to vaccinate
Pfizer model : Base case estimates for maternal vaccination,
VW 32 -36wGA, vaccine cost $295/dose & PSA
8Summary outcomes Base -Case
$/QALY gained $84,690
$/RSV -associated ED/OC visit
averted$6,145/ $2,101
$/RSV -associated LRTI
hospitalization averted$14,932
$/RSV -associated death averted>$7.7Million
NNV to avert an RSV -associated
ED/OC patient66 / 22
NNV to avert an RSV -associated
LRTI hospitalization159
NNV to avert an RSV -associated
death82,243
Probabilistic sensitivity analysis (PSA)87.1%
65.1%
34.7%
Difference in total QALYsDifference in total costs ( in millions )
Base -case Assuming 54.9% uptake in vaccinated group and 93.2% born ≥2 weeks after adm.
VW = vaccination window
wGA = weeks gestational age
LRTI= lower respiratory tract infection
OC = office clinic
ED = emergency department
NNV = Number needed to vaccinate
WTP = Willingness to pay
Pfizer and UM-CDC models comparison: base -case
selected outcome ratios for maternal vaccination
9UM-CDC model
Price per dose $295
VW=32 -36wGA
Year -round
administrationPfizer model
Price per dose $295
VW=32 -36wGA
Year -round
administration
$ / QALY gained $400,304 $84,690
$ / RSV LRTI hospitalization averted $68,423 $14,932
$ / Death averted among RSV LRTI hospitalized infants >$71.5Million >$7.7Million
NNV to prevent a
RSV LRTI associated hospitalization 242 159
Death among RSV LRTI hospitalized infants 241,989 82,243
Assuming 50% (UM -CDC) and 54.9% (Pfizer) uptake in vaccinated group and 100% (UM -CDC) to 93.2% (Pfizer) born ≥2 weeks after administration.
VW = Vaccination window
LRTI= lower respiratory tract infection
NNV = Number needed to vaccinate
Note: Both models vaccination window = 32 -36wGA only ( wGA = weeks gestational age)
$0 $100 $200 $300 $400 $500 $600 $700 $800
Probability of Prematurity
RSV QALYS Lost
RSVpreF vaccine cost/dose
Disease-specific inpatient costs (per inpatient case)
Vaccination Efficacy, Hospitalized RSV LRTI through 180 days
RSV-related QALYs lost Outpatient Child
Vaccination Efficacy, RSV MA-LRTI through 180 days
Proportion of RSV infections with an LRTI diagnosis…
RSV-related QALYs lost Outpatient Caregiver
RSV-related QALYs lost ED  ChildIncremental Cost -Effectiveness Ratio ( in thousands )
Low
HighUM-CDC model : One-way Sensitivity Analyses
Base case: $ 400,304/ QALY saved, vaccine price $ 295/dose
10MA= Medically -attended
LRTI= Lower respiratory tract infection
QALY= Quality adjusted life year$1.3
Million
Base -case $400,304
Pfizer model : One-way Sensitivity Analyses
Base case: $84, 690/QALY saved, Vaccine cost $295/dose
11CFR= Case fatality ratio
DoP = Duration of protection
VE= Vaccine efficacy
PT = Preterm
FT = Full termRSV-H = RSV -associated hospitalization
RSV-ED = RSV -associated emergency department care
RSV-OC = RSV -associated outpatient care15) VE lower bound
14) RSV-H medical care cost lower bound
13) US healthcare system perspective
12) DoP = 6 months
11) RSV-H CFR lower bound (overall = 0.1%)
10) Vaccine uptake 32 -36 wGA (uniform)
9) Disutilities form Glasser (RSV -H) and
Reigner (RSV -ED, RSV -OC)
8) Uptake = 100%
7)Base case
6) VE for late PT = for FT
5) Palivizumab scenario
4) DoP = 12 months
3) RSV-H CFR upper bound (overall=0.53%)
2) RSV-H medical care cost upper bound
1) VE upper bound
Base -case $84,690
Sensitivity / Scenario AnalysisCost per QALY
Pfizer and UM-CDC models comparison:
Selected influential inputs
12•RSV-hospitalization risk and RSV seasonality
•Vaccine efficacy
•Duration of protection and waning
•RSV Case fatality rate
•Medical cost of RSV hospitalization, ED and Outpatient care
•Vaccine associated adverse events
•Quality of life lost by patients and caregivers
Pfizer and UM-CDC: comparison of base -case risk of
RSV-related hospitalization by age and RSV Seasonality
13Risk of RSV Hospitalization : Pfizer and UM-CDC: Based on laboratory -confirmed RSV-associated hospitalization by age in months from New Vaccine Surveillance
Network (NVSN) data for children under 2 years of age (December 2016 to September 2020). Risk estimates are based only on RSV cases that manifest as LRTI.
RSV Seasonality: Pfizer :based on Midgley et al. J Infect Dis 2017. (data based in NRVSS) https://pubmed.ncbi.nlm.nih.gov/28859428/#full -view -affiliation -1
UM-CDC: based on National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)0%5%10%15%20%25%30%
Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections Pfizer
UM-CDC
00.0050.010.0150.020.0250.030.035
0 1 2 3 4 5 6 7 8 9 10 11Risk of RSV LRTI hospitalization
Age (in months)
Pfizer and UM-CDC:Differences in initial vaccine
efficacy
14NOTE: None of Pfizer Phase 3 (i.e., MATISSE) endpoint definitions overlapped ideally with the case definition used for the US burden data.
a. CDC: Average between efficacy for full term and preterm reported from Phase 3 were used. VE for RSV -LRTI hospitalization is an average over months 0-6 reported
in Phase 3 trial , and RSV -positive MA -LRTI for VE against RSV -LRTI in the ED and outpatient. Kampmann et al New England Journal of Medicine . 2023 Apr
b. Pfizer: Efficacy against severe RSV -positive MA -LRTI was used as a proxy for VE against RSV -LRTI requiring hospitalization, and efficacy against RSV -positive MA -LRTI
was used as a proxy for VE against RSV -LRTI treated in the ED. Pfizer: Kampmann et al New England Journal of Medicine . 2023 Apr
c. VE for late preterm infants was assumed to be 83.3% of corresponding values for full term infants. VE for URTI was assumed equal to VE for MA LRTI in ED care
d. Based on overall respiratory tract efficacy from phase 3 trial ( Kampmann et al New England Journal of Medicine . 2023 Apr )UM-CDCPfizer
Full Term Late Preterm
Initial vaccine efficacy against
RSV LRTI hospitalization (%)Month 0 = 81.0
Average Month 0-6 = 56.8 a88.1
Severe MA
RSV-LTRIb73.4
Severe MA
RSV-LRTI b, c
Initial vaccine efficacy against
Medically attended RSV associated LRTI for ED
and Outpatient care (%)Month 0 = 73.0
Average Month 0 -6 = 51.3 a47.6b39.7 c
For Scenario Analysis only : Initial efficacy
against RSV URTI treated in Outpatient care (%)37.9 d47.6b39.7 c
0%10%20%30%40%50%60%70%80%90%100%
0 3 6 9 12Efficacy
Month
Against medically-attended RSV-associated LRTI
Against hospitalizationaverage 6 -month efficacy =
efficacy against hospitalization
or medically -attended RSV -
associated LRTI
Zero
efficacy
The pink -shaded areas denote a higher level of uncertainty of the waning assumption beyond available phase 3 data
UM-CDC: Average between efficacy for full term and preterm were used for DoP for RSV -LRTI hospitalization over months 0 -6 and RSV -positive MA -LRTI for DoP
against RSV -LRTI in the ED and outpatient also over months 0 -6. Both r eported in Phase 3 trial , Kampmann et al New England Journal of Medicine . 2023 AprPfizer and UM-CDC: Assumption on duration of
protection ( DoP)
15Pfizer UM-CDC
VE against ED or OC             VE against hospitalization4 trial
endpoints
81.0
73.0
16UM-CDC Pfizer
Case fatality rate (CFR) among RSV -
hospitalized infants <12 months of age0.10%
(0.04% -0.20%)a0.10% (full term)
0.80% (all preterm) b
Medical costs per RSV hospitalization$11,487
($4,804 -$86,646)cAverage: $20,483 d
$13,171 –$33,876 (full term)
$19, 415 –$51,343 (late preterm)
Medical costs per RSV ED visit$563
($544 -$581)cAverage: $1,840 d
$1,620 –$2,520 (full term)
$1,787 –$2,779 (late preterm)
Medical costs per RSV outpatient visit$82
($46 -$118)cAverage: $348 d
$292 –$730 (full term)
$328 –$823 (late preterm)
a. RSV mortality per hospitalization: 0.10% (range 0.04 -0.20%) in 0 -5months, 0.10% (range 0.04 -0.20%) in 6 -11months.
b. Case fatality due to RSV -Hospital in full term infants per 100 cases = 0.1   (based on Li et al CEA -RSV in children 2022).  I n pre -term infants CFR per 100= 0.8 (assumes 16.3% of all RSV -Hosp
are among preterm)
c. Adapted from Bowser et al., J Infect Dis . 2022 Aug 15; 226(Suppl 2): S225 –S235 (A systematic review using studies from 2014 -2021.  Cost updated to 2022 using the GPD de flator)
d. Source: Pfizer data on file.  Costs in the base -case varied by age and term at birth. Weighted average cost among full and late preterm infants in commercially insured and Medicaid
populationsPfizer and UM-CDC models comparison:
Differences in key inputs
Pfizer and UM-CDC: Vaccine -associated adverse
events
17UM-CDC Pfizer Source
Rate of injection site reaction0.41
(0.38 –0.44)0.41
(0.38 –0.44}Pfizer Phase III Trial
Probability of healthcare visit, given
injection site reaction0.02
(0.015 –0.025 )0.02
(0.015 –0.025 )Curran, 2020
Cost of outpatient visit$367.76
(23.15 –1,758)$367.76
(23.15 –1,758)(Deluca, 2023) also in Pfizer CEA
technical report (August 2023)
Recipient time, physician office for
injection site reaction (hours)2
(1 –3)n/r Assumption
Hypothetical serious adverse event0.000001
(0 -0.0002)n/rBase: Prosser, 2006
High: 95% CI Phase 3 data for
RSV adult vaccines
Potential risk increase of prematurity0.0%
(0 –2%)n/rPfizer Phase III Trial
Kampmann et al New England
Journal of Medicine . 2023 Apr
Note: Values in bold are used for the base -case scenario. Range values in parenthesis for sensitivity analyses
n/r = not reported
Pfizer and UM-CDC: Quality of life lost ( in days )
by RSV LRTI outcome for patients & caregivers
18UM-CDC* Pfizer**
Outpatient: Child3.1
(1.8 -16.6)2.22
Outpatient: Caregiver1.5
(0 -9.1)1.5
ED: Child4.9
(2.9 –16.6)2.22
ED: Caregiver2.5
(0 -9.1)2.5
Hospitalized: Child6.2
(3.7 –26.5)5.7
Hospitalized: Caregiver2.4
(0 –13.6)2.4
Scenario Analysis : Vaccine -related increased
risk of prematurity ***11
(0 –438)n/r
* Base case values are from EGlasser et al 2022, lower values are based in Regnier et al 2013, higher values are based in JIVE (unpublished data)
**Patient values are base in Roy 2013, Caregiver values are based on Hutton. Economic Analysis of Nirsevimab in Pediatric Populations. ACIP; February 23, 2023.
Note: Values in bold are used for the base -case scenario. Range values in parenthesis for sensitivity analyses
*** Sources: Werner, et al 2015. Petrini et al, 2008, Hirvonen et al, 2014, Crump et al, 2021, Darcy -Mahoney et al, 2016, Carroll et al, 2009, Payakachat et al, 2014
n/r = not reported
19UM-CDC
UM-CDC model Base -case$400,304
ACost of RSV -LRTI hospitalization: $20,000 or $50,000 (i.e., 85% to 450% increase, base -case
cost= $11,487)$350,500 -$174,987
BUM-CDC model with same VE duration of protection as Pfizer : 6 months slowly, linearly
declining efficacy and declining faster after month 6 reaching 0% at month 9$286,769
CCFR among RSV LRTI hospitalization: 1% (base -case = 0.1%)$122,539
DCombining A and B vs. Combining A, B and C$233,736 -$52,108
EIncrease in the risk of prematurity in one-or two -percent points (base -case risk of prematurity
after vaccination = 0% increase )$874,609 -$1.3 Million
FVaccine administration timing: September -January vs. February -July (base -case, year -round) <$200,000 -$Millions
GVaccine cost = $50/dose or $500/dose (base -case vaccine cost = $295/dose) $65,304 -$680,609
HVE for URTI = 37.9% (Base -case = 0% VE against URTI) $279,490Pfizer and UM-CDC models comparison:
$/QALY for selected scenarios in UM-CDC model
20Pfizer
Pfizer model base -case $84,690
VE for late preterm infants assumed same as for full term infants a$73,404
Vaccine Efficacy :  80% or 120% of base case values $155,834  -$43,813
Trial -based VE over 6 months, then 0% VEor linear waning to 0% VE at 12 months$111,473  -$61,925
Overall CFR among RSV hospitalized:  0.1% or 0.53% b$102,431  -$52,000
Costs of RSV -Hospitalization 80% or 120% of base -case)$118,625  -$50,755
Vaccination window: 32 -36 wGA only ( uniform: 20% in each week ) c$91,036
Maternal vaccine and palivizumab in <1y infants vs.palivizumab only for prevention of RSV$66,796
a.Base -case assumes for late pre -term a VE =83%  of the VE for full term (VE = Vaccine efficacy)
b.CFR among RSV hospitalized:  0.1% (RR of RSV -H death = 1 for full term and preterm infants). For CFR 0.53% (using CFR values fro m full term = 0.3% and preterm = 1.7%)
c.wGA = weeks gestational age Pfizer and UM-CDC models comparison:
$/QALY for selected scenarios in Pfizer model  (I)
21Pfizer
APfizer model with selected UM-CDC Inputs $343,000
BPfizer model with selected UM-CDC Inputs except for Pfizer initial VE
assumptions$265,000
CPfizer model with selected UM-CDC Inputs except for Pfizer initial VE
assumptions and Pfizer DoP $173,000
DPfizer model with selected UM-CDC Inputs except for Pfizer initial VE
assumptions, Pfizer DoP and Pfizer Medical costs$83,000
EPfizer model with selected UM-CDC Inputs except for Pfizer initial VE
assumptions, Pfizer DoP ,  Pfizer Medical costs and Palivizumab use$67,000
DoP = Duration of protection
VE = vaccine efficacyPfizer and UM-CDC models comparison:
$/QALY for selected scenarios in Pfizer model  (II)
Limitations
22•Factors not considered that may result in overestimating the ICER
(underestimating the cost -effectiveness) of maternal vaccination
•In base -case: both models assumed
•No protection against URTI
•No benefits of vaccination for vaccinated pregnant women
•No out -of-pocket cost accrued by caregivers during infants RSV illness
•Neither model included RSV -related costs incurred after discharge from an
RSV-associated hospitalization or emergency department visit:
•Productivity losses incurred by caregivers after discharge
•Both models assumed no indirect effects of vaccination (i.e., no protection
against RSV transmission)
Conclusion
23•Differences in key inputs among Pfizer and UM-CDC models explain differences in results:
•Initial vaccine efficacy and assumptions about protection waning
•Medical costs
•Quality of life associated with RSV LRTI outcomes for patient and caregivers
•Vaccine related adverse events
•In addition, the UM-CDC also identified two important factors that could drive the results
•Hypothetically severe vaccine -associated adverse events
•Timing of vaccination to RSV season
•Base -case in both models:
•Maternal vaccination would significantly reduce RSV disease burden and costs in infants
•Data from clinical trials used in both models support the reduction in RSV disease and
associated costs
•Economic value of vaccinating pregnant people to protect infants could increase costs
•Reasonable vaccine price and duration of protection combined with careful design of
seasonal interventions would determine the cost-effectiveness value of routine
vaccination of pregnant people during the 32 -36wGA
Acknowledgements
From NCIRD/CDC
•Jefferson Jones
•Mila M. Prill
•Katherine E. Fleming -Dutra
•Jamison Pike
•Andrew Leidner
•Meredith McMorrow
Also:
•Maternal/Pediatric RSV working group members
24

End of Summary

Summary: Economics of Preventing Respiratory Syncytial  Virus Disease among US Infants by Maternal  Vaccination Prior to Birth A SUMMARY REPORT COMPARING MODELS FROM: Pfizer AND University of Michigan and CDC Ismael R. Ortega -Sanchez, PhD NCIRD/CDC ACIP Meeting, September 22, 2023 1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of  the Centers for Disease Control and Prevention.  National Center for Immunization &…