RSV Adults 04 Melgar 508

Centers for Disease Control and Prevention
Evidence to  Recommendations Framework
Respiratory  Syncytial Virus (RSV) in  Adults
GSK adjuvanted RSVpreF3 vaccine in older adults
Pfizer bivalent RSVpreF vaccine in older adults
Michael Melgar, MD
Lead, Adult RSV ACIP Work Group ACIP Meeting February 23, 2023

 Evidence to Recommendations (EtR ) Framework
Poli
cy Questions
Should vaccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1
dose IM), rather than no vaccine, be recommended in persons aged ≥65 years?
Should v
accination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1
dose IM), rather than no vaccine, be recommended in persons aged ≥60 years?
Should v
accination with Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM),
rather than no vaccine, be recommended in persons aged ≥65 years?
Should vaccination with Pfizer bivalent RS VpreF vaccine (120µg antigen, 1 dose IM),
rather than no vaccine, be recommended in persons aged ≥60 years?
2

       Evidence to Recommendations (EtR ) Framework
EtR Domain Question(s)
Public Health Problem Is the problem of public health importance?
Benefits and Harms How substantial are the desirable anticipated effects?
How substantial are the undesirable anticipated effects?
Do the desirable effects outweigh the undesirable effects?
Values Does the target population feel the desirable effects are large relative
to the undesirable effects?
Is there important variability in how patients value the outcome?
Acceptability Is the intervention acceptable to key stakeholders?
Feasibility Is the intervention feasible to implement?
Resource Use Is the intervention a reasonable and efficient allocation of resources?
Equity What would be in the impact of the intervention on health equity?
3

   Evidence to Recommendations (EtR ) Framework
EtR Domain
Public Health  Prob lem
Benefits  and Harms
Values Acceptability Feasibility Resource Use Equity Data on RSV in older adults will be presented
4

  Evidence to Recommendations (EtR ) Framework
EtR Domain
Public Health  Problem
Benefits  and Harms
Values
Acceptability
Feasibility
Resource Use
Equity Use of RSV vaccines broadly will be presented
5

   Evidence to Recommendations (EtR ) Framework
EtR Domain
Public Health  Problem
Benefits  and Harms
Values
Acceptability
Feasibility
Resource Use
Equity Manufacturer- specific data will be presented
6

   Public Health Problem
Is RSV among older adults of public health importance?

 Among adults ≥65   years of
age in the United States,
RSV  is associated with*…
*There  is substantial uncertainty
in burden  of disease,  reflected  in
wide ranges here.
6,000– 10,0001–3
deaths/year
60,000 –160,0004–8
hospitalizations/year
0.9–1.4 million5
medical encounters/year
5. McLaughlin et al, Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300
6. Zheng et al, Pneumonia (2022): https://doi.org/10.1186/s41479- 022-00098 -x
7. Branche et al, Clinical Infect Dis (2022): https://doi.org/10.1093/cid/ciab595
8. CDC RSV -NET data 2016– 2020 (unpublished) 1. Thompson et al, JAMA (2003): https://doi.org/10.1001/jama.289.2.179
2. Matias et al, Influenza Other Respi Viruses (2014): https://doi.org/10.1111/irv.12258
3. Hansen et al, JAMA Network Open (2022):
https://doi.org/10.1001/jamanetworkopen.2022.0527
4. Widmer et al, JAMA Network Open (2012): https://doi.org/10.1093/infdis/jis309 8

0 50 100 150 200 250 300 350 Hospitalizations per 100,000 237 to 325
42 to 53
7 to 11 26 to 36 50 to 67 69 to 84 111 to 133
18-49 yr 50-59 yr 60-64 yr 65-69 yr 70-79 yr 80+ yr Overall
2016-17 2017-18 2018-19 2019-20

             RSV-associated hospitalization rates by adult age group,
RSV-NET 2016–2020
RSV-NET: unpublished data; https://www.cdc.gov/rsv/research/rsv-net/overview-methods.html.
Rates are adjusted for the frequency of RSV testing during recent prior seasons and the sensitivity of RSV diagnostic tests.. Slide credit: Fiona Havers 9

 25 23
20 20 18
15
5 10
5 31
0
18-49 50-64 ≥65
Age group (years)
ICU admission Death
Slide credit: Fiona Havers Percent

 Outcomes among adults ≥18 years hospitalized for
RSV: RSV -NET 2017–18 to 2019–20 seasons (n=8,214)
Severe outcomes
frequent among adults of all ages hospitalized for RSV
10

     Adults with certain underlying medical conditions are
at higher risk of RSV hospitalization
Immune compromise, especially hematopoietic stem cell transplant and
solid organ transplant
Cardiovascular disease (e.g., congestive heart failure)
Diabetes mellitus
Chronic obstructive pulmonary disease (COPD)
Asthma
1. Anderson et al, Diagn Microbiol Infect Dis (2016): https://doi.org/10.1016/j.diagmicrobio.2016.02.025
2. Prasad et al, Clin Infect Dis (2020): https://doi.org/10.1093/cid/ciaa730
3. Kujawski et al, Plos One (2022): https://doi.org/10.1371/journal.pone.0264890
4. Branche et al, Clin Infect Dis (2022): https://doi.org/10.1093/cid/ciab595 11

  Summary
RSV is a frequent, often unrecognized, cause of severe respiratory
illness, with incidence increasing with age among older adults
High proportion of those hospitalized with RSV have severe outcomes, including ICU admission and death
Death is more common with increasing age
12
   Public Health Problem- Work Group Interpretation
Is RSV   disease   of public   health   importance   among   adults   aged   ≥65
years?
No Prob
ably
No Pro
bably
Yes Ye
s Va
ries Don
’t
know
13
 Benefits and Harms
-How substantial are the desirable anticipated effects?
-How substantial are the undesirable anticipated effects?
-Do the desirable effects outweigh the undesirable effects?

   Benefits and Harms
GSK adjuvanted RSVpreF3 vaccine
– Grading of Recommendations, Assessment, Development and
Evaluation ( GRADE) Summary
– Number-needed-to -vaccinate (NNV) analysis
Pfizer bivalent RSVpreF vaccine
– GRADE Summary
– NNV analysis
15
16

  GRADE Framework: PICO Question
Population
Intervention
Comparison
Outcomes Persons aged ≥60 years
GSK RSVpreF3 vaccine (120 μg antigen + AS01E adjuvant, 1 dose IM)
-or-
Pfi
zer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM)
No RSV vaccine
RS
V lower respiratory tract illness/disease (LRTI/LRTD)
Medically attended RSV LRTI/LRTD
Hospitalization for RSV respiratory illness
Severe RSV respiratory illness requiring supplemental O2 or other
respiratory support
Death due to RSV respiratory illness
Serious Adverse Events (SAEs)
Inflammatory neuropathy (e.g., Guillain -Barré syndrome)
Reactogenicity (grade ≥3)
GRADE: GSK adjuvanted RSVpreF3
17

     GSK, Benefits: vaccine efficacy estimates
Outcome Importance Data sources Vaccine efficacy estimatea
(95% confidence interval) Concerns in certainty
assessment
Benefits
RSV Lower Respiratory Tract Disease (LTRD) Critical
One phase 3 RCTb 82.5% (60.9%, 92.1%) Indirectness (serious)c
Medically attended RSV LRTD Critical One phase 3 RCTb 87.5% (58.4%, 96.2%) Indirectness (serious)c
Hospitalization for RSV respiratory illness Important
One phase 3 RCTb Unable to evaluated
Severe RSV respiratory illness requiring O2/respiratory support Important
One phase 3 RCTb Unable to evaluatee
Death due to RSV respiratory illness Important One phase 3 RCTb Unable to evaluatef
RCT: Randomized control trial
a Efficacy estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3 trial int erim analysis. Data provided by manufacturer.
Efficacy was calculated as 1 – relative risk. Events of each outcome were included if they occurred on or after day 15 after injection.
b Papi A, Ison MG, Langley JM, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. 2023. NEJM. https://doi.org/10.1056/nejmoa2209604
c Underrepresentation of adults aged ≥80 years, exclusion of persons with immune compromise.
d Three RSV -associated hospitalizations occurred in the modified exposed set up to the data lock point for the interim analysis. Information was not provided by study arm
(intervention vs. placebo) to avoid unblinding of cases.
e 31 cases of LRTD requiring oxygen supplementation were identified; 4 of the 31 cases were associated with RSV. All 4 cases oc curred in the placebo arm. Measures of
relative and absolute risk were not calculated due to small number of events.
f No RSV -associated deaths were recorded in the interim analysis. 18

       GSK, Harms: relative risk
Outcome Importance Data sources Relative risk estimatea
(95% confidence interval) Concerns in certainty
assessment
Harms
Serious adverse events (SAEs) Critical One phase 3 RCT,
one phase 1/2 RCT 1.03 (0.92, 1.17) None serious
Inflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb
Reactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 4.10 (1.99, 8.45) None serious
RCT: Randomized control trial
a Pooled relative risk estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3 trial interim analysis ( Papi A, et al. NEJM
2023 https://doi.org/10.1056/nejmoa2209604), as well as from a placebo -controlled phase 1/2 dosing selection study (Leroux -Roels I, et al. J Infect Dis. 2022
https://doi.org/10.1093/infdis/jiac327). Data provided by manufacturer.
b No events recorded in studies included in GRADE. One event of Guillain- Barré syndrome recorded in a recipient of the investigational vaccine in an open label trial without a
placebo arm. This study was not included in GRADE assessment due to lack of an unvaccinated comparator.
19

     GSK, Harms: relative risk
Outcome Importance Data sources Relative risk estimatea
(95% confidence interval) Concerns in certainty
assessment
Harms
Serious adverse events (SAEs) Critical One phase 3 RCT,
one phase 1/2 RCT 1.03 (0.92, 1.17) None serious
Inflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb
Reactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 4.10 (1.99, 8.45) None serious
RCT: Randomized control trial
a Pooled relative risk estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3 trial interim analysis ( Papi A, et al. NEJM
2023 https://doi.org/10.1056/nejmoa2209604), as well as from a placebo -controlled phase 1/2 dosing selection study (Leroux -Roels I, et al. J Infect Dis. 2022
https://doi.org/10.1093/infdis/jiac327). Data provided by manufacturer.
b No events recorded in studies included in GRADE. One event of Guillain- Barré syndrome recorded in a recipient of the investigational vaccine in an open label trial without a
placebo arm. This study was not included in GRADE assessment due to lack of an unvaccinated comparator.
Total of 1 case of inflammatory neuropathy among approximately
15,000 investigational vaccine recipients across all clinical trials 20

    Summary of GRADE for GSK RSVPreF3 vaccine in older adults
Outcome Importance Design
(# of studies)Findings Evidence type
Benefits
RSV Lower Respiratory Tract
Disease (LTRD) Critical RCT (1) GSK RSVpreF3 likely reduces RSV LRTD. Moderate
Medically attended RSV LRTD Critical RCT (1) GSK RSVpreF3 likely reduces medically attended RSV LRTD. Moderate
Hospitalization for RSV respiratory illness Important RCT (1) Only three events, unknown whether in vaccine or placebo arm Unable to
evaluate
Severe RSV respiratory illness requiring O2/respiratory support Important RCT (1) Measures of relative and absolute risk not calculated due to small number of events. Unable to
evaluate
Death due to RSV respiratory illness Important RCT (1) No events observed Unable to
evaluate
Harms
Serious adverse events Critical RCT (2) GSK RSVpreF3 results in little to no differences in SAEs. High
Inflammatory neuropathy Important RCT (2) No events observed in placebo -controlled trials. Single case
observed in an open- label uncontrolled study. Unable to
evaluate
Reactogenicity (grade ≥3) Important RCT (2) GSK RSVpreF3 increases severe reactogenicity events. High
21

 Summary of GRADE for GSK RSV vaccine in older adults
Overall evidence rating: Moderate certainty 22

       Number needed to vaccinate (NNV): GSK RSVpreF3
Derived from cost effectiveness analysis performed by U. Michigan
Time horizon: one year
Number of vaccinations
required to prevent… Adults aged ≥65 years Adults aged ≥60 years
1 RSV outpatient visita 84 vaccinations 90 vaccinations
1 RSV hospitalizationb 1,097 vaccinations 1,348 vaccinations
1 RSV deathc 21,442 vaccinations 27,284 vaccinations
a Incidence rates of RSV illness requiring outpatient visit taken from McLaughlin et al, OFID (2022) (unadjusted for RSV under -detection by NP swab RT-PCR). Vaccine efficacy (VE) against
this outcome assumed to be equal to that against medically attended acute respiratory illness (ARI) caused by RSV (GSK AReSVi-006 trial, unpublished).
b Incidence rates of RSV hospitalization taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated hospitalization assumed to be equal to that against medically attended
lower respiratory tract disease (LRTD) caused by RSV (GSK AReSVi-006 trial, unpublished).
c Probability of in-hospital death among adults hospitalized for RSV taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated death assumed to be equal to that against
medically attended lower respiratory tract disease (LRTD) caused by RSV (GSK AReSVi-006 trial, unpublished). 23

  Benefits and Harms GSK adjuvanted RSVpreF3 vaccine
How substantial are the desirable anticipated effects among adults
ag
ed ≥65 years (relative to no RSV vaccine)?
– How substantial is the anticipated protective effect against:
• R
SV lower respiratory tract disease (LRTD)
• Medically attended RSV LRTD
• Hospitalization for RSV respiratory illness
• Severe RSV respiratory illness requiring supplemental O2/respiratory
support
• Death due to RSV respiratory illness
Minimal Small Moderate Large Varies Don’ t know
24

  Benefits and Harms GSK adjuvanted RSVpreF3 vaccine
How substantial are the undesirable anticipated effects among
ad
ults aged ≥65 years (relative to no RSV vaccine)?
– How substantial is the anticipated effect on:
• S
erious Adverse Events (SAEs)
• Inflammatory neuropathy (e.g., Guillain- Barré Syndrome)
• Reactogenicity (grade ≥3)
Minimal Small Mode rate Large Varies Don’t know
Minority opinion 25

  Benefits and Harms GSK adjuvanted RSVpreF3 vaccine
Do the desirable effects outweigh the undesirable effects among
adu
lts aged ≥65 years?
– What
is the balance between the desirable effects relative to
the u
ndesirable effects?
Favors  intervention  (GSK RSVpreF3  vaccine)
Favors  comparison (no  vaccine)
Favors both
Favors neither
Unclear
Minority opinion 26
 GRADE: Pfizer bivalent RSVpreF
27

     Pfizer, Benefits: vaccine efficacy estimates
Outcome Importance Data sources Vaccine efficacy estimatea
(95% confidence interval) Concerns in certainty
assessment
Benefits
RSV Lower Respiratory Tract Illness (LRTI)
b Critical One phase 3 RCT 85.7% (37.9%, 98.4%) Indirectness (serious)c
Medically attended RSV LRTIb Critical One phase 3 RCT 80.0% (6.3%, 97.9%) Indirectness (serious)c
Hospitalization for RSV respiratory illness Important Counts not
provided Unable to evaluated
Severe RSV respiratory illness
requiring O2/respiratory support Important Counts not
provided Unable to evaluated
Death due to RSV respiratory illness Important One phase 3 RCT Unable to evaluatee
RCT: Randomized control trial
a Efficacy estimates were independently calculated using counts of events and person- time observation in the Pfizer pivotal phase 3 trial interim analysis. Data provided by
manufacturer. Efficacy was calculated as 1 – incidence rate ratio. Events of each outcome were included if they occurred on or a fter day 15 after injection.
b Pfizer pivotal phase 3 trial included co -primary outcomes of LRTI with ≥2 lower respiratory signs or symptoms, and LRTI with ≥3 lower respiratory signs or symptoms. In
GRADE, the outcome of LRTI with ≥3 lower respiratory signs or symptoms was used.
c Underrepresentation of adults aged ≥80 years, exclusion of persons with immune compromise.
d Counts of event were not provided by manufacturer.
e No RSV -associated deaths were recorded in the interim analysis. 28

         Pfizer, Harms: relative risk
Outcome Importance Data sources Relative risk estimatea
(95% confidence interval) Concerns in certainty
assessment
Harms
Serious adverse events (SAEs) Critical One phase 3 RCT
one phase 1/2 RCT 1.01 (0.88 to 1.16) None serious
Inflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb
Reactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 1.47 (0.88 to 2.46) Imprecision (serious)c
RCT: Randomized control trial
a Pooled relative risk estimates were independently calculated using counts of events and participants in the Pfizer pivotal phas e 3 trial interim analysis, as well as from a
placebo- controlled phase 1/2 formulation selection study ( Falsey A, et al. J Infect Dis. 2022 https://doi.org/10.1093/infdis/jiab611p ). Data provided by manufacturer.
b In the Pfizer pivotal phase 3 trial interim analysis, 2 events of Guillain -Barré syndrome were recorded in the intervention arm , compared with zero in the placebo arm. No
events were recorded in the phase 1/2 formulation selection study. Measures of relative and absolute risk were not calculated due to small number of events.
c 95% confidence interval for measure of absolute risk included potential for both benefit and harm.
29

         Pfizer, Harms: relative risk
Outcome Importance Data sources Relative risk estimatea
(95% confidence interval) Concerns in certainty
assessment
Harms
Serious adverse events (SAEs) Critical One phase 3 RCT
one phase 1/2 RCT 1.01 (0.88 to 1.16) None serious
Inflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb
Reactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 1.47 (0.88 to 2.46) Imprecision (serious)c
RCT: Randomized control trial
a Pooled relative risk estimates were independently calculated using counts of events and participants in the Pfizer pivotal phas e 3 trial interim analysis, as well as from a
placebo- controlled phase 1/2 formulation selection study ( Falsey A, et al. J Infect Dis. 2022 https://doi.org/10.1093/infdis/jiab611p ). Data provided by manufacturer.
b In the Pfizer pivotal phase 3 trial interim analysis, 2 events of Guillain -Barré syndrome were recorded in the intervention arm , compared with zero in the placebo arm. No
events were recorded in the phase 1/2 formulation selection study. Measures of relative and absolute risk were not calculated due to small number of events.
c 95% confidence interval for measure of absolute risk included potential for both benefit and harm.
Total of 2 cases of inflammatory neuropathy among approximately
26,000 investigational vaccine recipients across all clinical trials 30

    Summary of GRADE for Pfizer RSV vaccine in older adults
Outcome Importance Design
(# of studies)Findings Evidence type
Benefits
RSV Lower Respiratory Tract
Illness (LRTI) Critical RCT (1) Pfizer RSVpreF likely reduces RSV LRTI. Moderate
Medically attended RSV LRTI Critical RCT (1) Pfizer RSVpreF likely reduces medically attended RSV LRTI. Moderate
Hospitalization for RSV respiratory illness Important No data Unable to
evaluate
Severe RSV respiratory illness requiring O2/respiratory support Important No data Unable to
evaluate
Death due to RSV respiratory illness Important RCT (1) No events observed Unable to
evaluate
Harms
Serious adverse events (SAEs) Critical RCT (2) Pfizer RSVpreF results in little to no difference in SAEs. High
Inflammatory neuropathy Important RCT (2) Measures of relative and absolute risk not calculated due to
small number of events. Unable to
evaluate
Reactogenicity (grade ≥3) Important RCT (2) Pfizer RSVpreF likely increases severe reactogenicity events. Moderate
31

 Summary of GRADE for Pfizer RSV vaccine in older adults
Overall evidence rating: Moderate certainty 32

                Number needed to vaccinate (NNV): Pfizer RSVpreF
Derived from cost effectiveness analysis performed by U. Michigan
Time horizon: one year
Number of vaccinations
required to prevent… Adults aged ≥65 years Adults aged ≥60 years
1 RSV outpatient visita 95 vaccinations 103 vaccinations
1 RSV hospitalizationb 1,275 vaccinations 1,567 vaccinations
1 RSV deathc 24,927 vaccinations 31,717 vaccinations
a Incidence rates of RSV illness requiring outpatient visit taken from McLaughlin et al, OFID (2022) (unadjusted for RSV under -detection by NP swab RT-PCR). Vaccine efficacy (VE) against
this outcome assumed to be equal to that against medically attended acute respiratory illness (ARI) caused by RSV (Pfizer REN OIR trial, unpublished).
b Incidence rates of RSV hospitalization taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated hospitalization assumed to be equal to that against medically attended
lower respiratory tract illness (LRTI) with ≥3 symptoms, caused by RSV (Pfizer RENOIR trial, unpublished).
c Probability of in-hospital death among adults hospitalized for RSV taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated death assumed to be equal to that against
medically attended lower respiratory tract illness (LRTI) with ≥3 symptoms, caused by RSV (Pfizer RENOIR trial, unpublished). 33

  Benefits and Harms Pfizer bivalent RSVpreF vaccine
How substantial are the desirable anticipated effects among adults
ag
ed ≥65 years (relative to no RSV vaccine)?
– How substantial is the anticipated protective effect against:
• R
SV lower respiratory tract disease (LRTD)
• Medically attended RSV LRTD
• Hospitalization for RSV respiratory illness
• Severe RSV respiratory illness requiring supplemental O2/respiratory
support
• Death due to RSV respiratory illness
Minimal Small Moderate Large Varies Don’t know
34

  Benefits and Harms Pfizer bivalent RSVpreF vaccine
How substantial are the undesirable anticipated effects among
ad
ults aged ≥65 years (relative to no RSV vaccine)?
– How substantial is the anticipated effect on:
• S
erious Adverse Events (SAEs)
• Inflammatory neuropathy (e.g., Guillain- Barré Syndrome)
• Reactogenicity (grade ≥3)
Minimal Small Mod erate Large Varies  Don’t know
Minority opinion 35

  Benefits and Harms Pfizer bivalent RSVpreF vaccine
Do the desirable effects outweigh the undesirable effects among
adu
lts aged ≥65 years?
– What
is the balance between the desirable effects relative to
the u
ndesirable effects?
Favors  intervention  (Pfizer  RSVpreF  vaccine)
Favors comparison (no vaccine)
Favors both
Favors neither
Unclear
Minority opinion 36

 Values
Do older adults feel the desirable effects of RSV vaccination are
large relative to the undesirable effects?
Is there important variability in how older adults value the main
outcomes?

    Survey of vaccination intent for an RSV vaccine among
U.S. adults aged ≥60 years
Designed to assess vaccination intentions for a hypothetical RSV vaccine
Data collection period: December 23– 31, 2022
Final sample: 586 respondents (98.7% completion rate)
GENDER RACE/ETHNICITY AGE
56.3% Female
43.7% Male or other
gender identity 74.9% N on-Hispanic White
12.4% Non- Hispanic Black
9.1% Hispanic 70.6% 60 –70 years
29.4% ≥70 years
CDC and University of Iowa/RAND survey, unpublished 38

Definitely or
probably would get vaccinated
Unsure
Definitely or probably would not
get vaccinated
39

  68% of respondents said they ‘definitely’ or ‘probably’
would get vaccinated if a safe and effective FDA-
approved RSV vaccine was available
CDC and University of Iowa/RAND survey, unpublished

Definitely or
probably would get vaccinated
Unsure
Definitely or probably would not
get vaccinated
40
  77% said they ‘definitely’ or ‘probably’ would get an
RSV vaccine if it were recommended by a healthcare
provider
CDC and University of Iowa/RAND survey, unpublished

    % of respondents who expressed hesitancy to receive an RSV vaccine (n=378)
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
I don’t know enough about RSV
Long-term safety
Short-term safety
Cost concerns
Don’t trust an RSV vaccine
I’ve gotten too many vaccines
RSV vaccine might cause RSV
RSV vaccine might make infection worse
None of these
An RSV vaccine wouldn’t work well
Other
I don’t like needles
Not at risk of getting RSV
Would not get sick if I got RSV
Against my religious beliefs
I’ve already had RSV
No time to get vaccinated
RSV is not real 41.0%
39.4%
29.1%
13.0%
11.9%
11.1%
9.3%
9.3% 9.3%
5.8%
5.6%
5.3%
4.5%
4.2%
1.6%
0.8% 0.8%
0.5%
   Lack of RSV knowledge and safety concerns were
among the top reasons for not wanting an RSV vaccine
CDC and University of Iowa/RAND survey, unpublished 41

   Values

–
–Do older adults feel that the desirable effects of RSV vaccination are
lar
ge relative to the undesirable effects?
 How d
o older adults view the balance of desirable versus
un
desirable effects?
 Woul
d older adults feel that the benefits outweigh the harms?
No Probably no Probably Yes Yes Varies Don’t know
42

  Values
Is there important uncertainty about, or variability in, how much older
ad
ults value the main outcomes?
– Is th
ere evidence that the variability is large enough to lead to
dif
ferent decisions?
Important  uncertainty or variability
Probably important  uncer tainty  or  variability
Probably not important uncertainty or variability
No important uncertainty or variability
No known undesirable outcomes
43
 Acceptability
Would recommending RSV vaccines for older adults be
acceptable to key stakeholders?

  Vaccine Policy Collaborative Initiative
Survey of physicians, February–March 2017
National network of 930 primary care physicians who agreed to
participate in surveys about vaccine policy issues
– 620 physicians (67%) completed the survey
– Responses analyzed from 317 respondents (51%) who reported
caring for ≥1 adult patient with possible RSV in the preceding 12
months
Hurley LP , Allison MA, Kim L, et al. Primary care physicians’ perspectives on respiratory syncytial virus (RSV) disease in ad ults and a potential RSV vaccine for adults. 2019 Vaccine
37(4): 565- 570. ISSN 0264- 410X. https://doi.org/10.1016/j.vaccine.2018.12.031 . 45
Physician Perception of Importance of RSV as a pathogen in
the following groups of patients, United States, 2017 (n = 317)
A majority of physicians believed
that RSV was a very important pathogen in adults of any age with an immunocompromising
condition (57%) and adults aged
≥65 years with cardiopulmonary
disease (56%).

Hurley LP , Allison MA, Kim L, et al. Primary care physicians’ perspectives on respiratory syncytial virus (RSV) disease in ad ults and a potential RSV vaccine for adults. 2019 Vaccine
37(4): 565- 570. ISSN 0264- 410X. https://doi.org/10.1016/j.vaccine.2018.12.031. 46
Physician Perception of Importance of RSV as a pathogen in
the
following groups of patients, United States, 2017 (n = 317)
One third of physicians believed
that RSV was a very important pathogen in adults 50–64 years
with cardiopulmonary disease
(35%) and adults ≥65 years
without cardiopulmonary
disease (31%).

Hurley LP , Allison MA, Kim L, et al. Primary care physicians’ perspectives on respiratory syncytial virus (RSV) disease in ad ults and a potential RSV vaccine for adults. 2019 Vaccine
37(4): 565- 570. ISSN 0264- 410X. https://doi.org/10.1016/j.vaccine.2018.12.031. 47

    Acceptability
Would r ecommending RSV vaccines for adults aged ≥65 years be
acceptable to key stakeholders?
– Are th
ere key stakeholders that would not accept the distribution of
bene
fits and harms?
– Are th
ere key stakeholders that would not accept the undesirable
effects in the short term for the desirable effects (benefits) in the
fu
ture?
No Probably No Probably Yes Yes Varies Don’t know
48
  Feasibility
Is RSV vaccination for older adults feasible to implement?

   Barriers to implementation of a novel RSV vaccine may
include:
Vaccine storage and handling requirements
Complexity of the adult vaccination schedule (including coadministration)
Financial barriers
50
51

  Storage & handling requirements
GSK RSVpreF3 Pfizer RSVpreF
Supplied as single dose Supplied as single dose, or as a 5-pack or
10-pack of single- dose kits
Reconstitution required: single dose vial
of lyophilized powder (antigen component) + single dose vial of liquid (adjuvant component) Reconstitution required: single dose vial of lyophilized powder, reconstitution supplies included in kit
Both components should be refrigerated (2–8°C) in original container, protected
from light Product should be refrigerated (2–8° C) in
original container, protected from light
After reconstitution, the product should be administered within 4 hours, otherwise
discarded After reconstitution, the product should be administered within 4 hours, otherwise
discarded

      Older adult routine immunization schedule is
becoming more complex
https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html
50-64 years ≥65 years
Influenza
inactivated (IIV4) or
Influenza recombinant (RIV4) 1 dose annually
Tetanus, diphtheria, pertussis
(Tdap or Td) 1 dose Tdap, then Td or Tdap booster every 10 years
Zoster recombinant
(RZV) 2 doses
Pneumococcal
(PCV15, PCV20,
PPSV23) 1 dose PCV15 followed by PPSV23
OR
1 dose PCV20 ( see notes ) 1 dose PCV15 followed by PPSV23
OR
1 dose PCV20
Potential fall or other regularly scheduled COVID -19 vaccine
Clinicians may face competing vaccine priorities 52

        Time/financial barriers
Older adults without health insurance coverage may experience financial
hardship obtaining an RSV vaccine.
Financial hardship may also arise if vaccine recipients need to take time off
from work to receive an RSV vaccine, or due to post-vaccination reactogenicity.
53

  Feasibility
Is the GSK adjuvanted RSVpreF3 vaccine feasible to implement among
adul
ts aged ≥65 years?
Is th
e Pfizer bivalent RSVpreF vaccine feasible to implement among adults
aged
 ≥65 years?
No Probably No Pr obably Yes Ye s Va ries Don’ t know
54

 Resource Use
Is an RSV vaccine program for older adults a reasonable and
efficient allocation of resources?

 Work group considerations
RSV vaccination for older adults could be a cost-effective intervention
There is substantial uncertainty in the net societal costs of an RSV
vaccination program for older adults, driven by:
– Uncertainty in incidence of severe RSV illness
– Uncertainty in vaccine acquisition cost
– Uncertainty in duration of protection from RSV vaccination
None of the three models incorporated medical costs of longer -term
sequelae of RSV infection (e.g., admission to skilled nursing facilities)
Vaccination of older age groups would be more cost effective than vaccination of younger age groups
56

 Resource Use

Is use of GSK a djuvanted RSVpreF3 vaccine among adults aged ≥65
yea
rs a reasonable and efficient allocation of resources, compared with
no
 RSV vaccine?
Is
 use of Pfizer bivalent RSVpreF vaccine among adults aged ≥65
years a reasonable and efficient allocation of resources, compared with
no
 RSV vaccine?
No Probably No Prob ably Yes Yes Var ies Don’t kno w
57

  Equity
What would be the impact on health equity of recommending
RSV vaccines in older adults?

    Incidence of RSV
hospitalization is higher among
persons in low -
income ZIP codes
Zheng Z, et al. Estimated incidence of respiratory hospitalizations attributable to RSV infections across age and socioeconom ic groups.
Pneumonia (Nathan). 2022 Oct 25;14(1):6. doi: 10.1186/s41479- 022-00098 -x. 59

  Age of adults hospitalized with RSV, by race and
ethnicity, RSV -NET
N Median age, years
(interquartile range)
All 9,163 70 (58–81)
Race and ethnicity
White, non-Hispanic 5,596 73 (62–83)
Black, non-Hispanic 1,731 60 (50–70)
Hispanic 713 65 (50–77)
Asian or Pacific Islander, non-Hispanic 518 77 (64–85)
American Indian or Alaska Native, non-Hispanic 56 57 (47–71)
CDC RSV -NET data 2015–2020 (unpublished) 60

  Age of adults hospitalized with RSV, by race and
ethnicity, RSV -NET
N Median age, years
(interquartile range)
All 9,163 70 (58–81)
Race and ethnicity
White, non-Hispanic 5,596 73 (62–83)
Black, non-Hispanic 1,731 60 (50–70)
Hispanic 713 65 (50–77)
Asian or Pacific Islander, non-Hispanic 518 77 (64–85)
American Indian or Alaska Native, non-Hispanic 56 57 (47–71)
CDC RSV -NET data 2015–2020 (unpublished) 61

   Chronic medical conditions associated with increased risk of RSV disease
are more prevalent in U.S. adults in certain demographic groups
Heart failure Coronary heart
disease Diabetes mellitus COPD
a Asthma
Black, non-Hispanic
b ↑c ↑↑c ↑c,d ↑e,f
AI/ANg, non -
Hispanicb ↑↑h ↑↑h ↑e
Hispanica ↑c,d,h ↓e,f
Asian, non -
Hispanicb ↓c ↓c ↑c,d ↓h ↓e
Lower income or SES
i ↑j ↑h,j,k ↑h,l ↑h ↑e,f,h
a COPD = chronic obstructive pulmonary disease
b Compared with non- Hispanic White adults
c Tsao et al, Circulation (2022): https://doi.org/10.1161/cir.0000000000001052
d Cheng et al, JAMA (2019): https://doi.org/10.1001/jama.2019.19365
e https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm
f Bhan et al, Am J Public Health (2015): https://doi.org/10.2105/ajph.2014.302172
g AI/AN = American Indian or Alaska Native h NHIS 2018: https://www.cdc.gov/nchs/nhis/shs/tables.htm
i SES = socio -economic status
j Abdalla et al, JAMA Netw Open (2020):
https://doi.org/10.1001%2Fjamanetworkopen.2020.18150
k Hamad et al, JAMA Cardiol (2020): https://doi.org/10.1001/jamacardio.2020.1458
l Beckles and Chou, MMWR (2016): http://dx.doi.org/10.15585/mmwr.mm6545a4 62

      Access to an RSV vaccine may be determined by health
insurance coverage
0% 5% 10% 15% 20%
55-64 ≥65 Percentage of U.S.
adults without health
insurance
Age group (years) American Indian or Alaska Native,
non-Hispanic
Hispanic
Black, non-Hispanic
Asian, non-Hispanic
White, non-Hispanic
U.S. Census Bureau, 2021 American Community Survey 1- year estimates: https://data.census.gov/table 63

     Access to an RSV vaccine may be determined by health
insurance coverage
Age group
(years) Percentage of population without health insurance
Below
poverty 1.0– 1.9x
poverty 2.0– 2.9x
poverty ≥3.0x poverty
19–64 23.0% 22.2% 16.8% 6.5%
≥65 2.3% 1.0% 0.9% 0.5%
Example income for 2 -person household $18,145 $36,290 $54,435
without children, age <65 years
U.S. Census Bureau, 2021 American Community Survey 1- year estimates: https://data.census.gov/table 64

   Equity
What would be the impact on health equity of recommending RSV
vacc
ines in adults aged ≥65 years?
Reduced
Probably reduced
Probably no impact
Probably increased
Increased
Varies
Don’t know
65
Summary

  Domain Question Work Group Judgements
Adults aged ≥65 years GSK Pfizer
Public Health
Problem Is RSV of public health importance? Yes
Benefits and
Harms How substantial are the desirable anticipated effects? Moderate – Large Moderate – Large
How substantial are the undesirable anticipated effects? Minimal – Small Minimal – Small
Do the desirable effects outweigh the undesirable effects? Favors intervention Favors intervention
What is the overall certainty of the evidence profile? Moderate Moderate
Values Does the target population feel the desirable effects are large
relative to the undesirable effects? Yes/Probably yes
Is there important variability in how patients value the outcomes? Important variability/Probably important variability
Acceptability Is the intervention acceptable to key stakeholders? Yes/Probably yes
Feasibility Is the intervention feasible to implement? Yes/Probably yes Yes/Probably yes
Resource Use Is the intervention a reasonable and efficient allocation of resources? Yes/Probably yes Yes/Probably yes
Equity What would be the impact on health equity? Increased/Probably increased
67

 Work Group interpretation
GSK’s adjuvanted RSVpreF3 and Pfizer’s bivalent RSVpreF vaccines both
have demonstrated significant efficacy against lower respiratory tract
illness caused by RSV among older adults
– Trials underpowered to show efficacy against RSV hospitalization
– Groups at highest risk of severe RSV disease were under- represented in
clinical trials
At least one case of inflammatory neuropathy has been observed among recipients of each investigational vaccine
If licensed, post licensure surveillance for both safety and vaccine
effectiveness will be critical
68

          Choice of age threshold at which to recommend* RSV vaccines
Pros Cons
Age ≥65 years • Greater risk of RSV disease and therefore
more favorable population- wide balance
of risks and benefits of vaccination (in light of 1– 2 cases of inflammatory
neuropathy observed)
• Aligns with licensure for adjuvanted and high- dose influenza vaccines and age -
based pneumococcal vaccination • Lost opportunity to prevent additional disease in the 60–64 age group, who are
disproportionately from racial and ethnic groups impacted by RSV at earlier ages
Age ≥60 years • Potential to prevent a greater total burden of disease (e.g., number of hospitalizations)
• Increases access to adults 60 –64 with
medical risk factors for severe RSV disease (disproportionately in racial and ethnic groups impacted by RSV at earlier ages) • Uninsured adults would have difficulty obtaining vaccination (disproportionately aged 60–64 in racial, ethnic and socioeconomic
groups at greater risk)
• May experience more difficulty achieving clinician adoption of the recommendation among patients 60–64
• Less efficient allocation of societal resources
*FDA has not yet completed review of safety and efficacy data for the GSK RSVpreF3 vaccine and the Pfizer RSVpreF
vaccine. ACIP recommendations would be made only if the vaccines are approved and licensed by the FDA.
69

 Evidence to Recommendations Framework
Summary: Work Group Interpretations (GSK RSVpreF3)
70

    Evidence to Recommendations Framework
Summary: Work Group Interpretations (GSK RSVpreF3)
Among adults aged ≥65 years: Minority opinion
Balance of
consequences Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably
outweigh
desirable
consequences in
most settings The balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
consequences
probably
outweigh
undesirable
consequences in
most settings Desirable
consequences
clearly outweigh
undesirable
consequences in
most settings There is
insufficient
evidence to
determine the
balance of
consequences
Among adults aged ≥60 years:
Balance of
consequences Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably
outweigh
desirable
consequences in
most settings The balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
consequences
probably
outweigh
undesirable
consequences in
most settings Desirable
consequences
clearly outweigh
undesirable
consequences in
most settings There is
insufficient
evidence to
determine the
balance of
consequences
71

      Evidence to Recommendations Framework
Summary: Work Group Interpretations (GSK RSVpreF3)
Type of recommendation, adults aged ≥65 years
We do not recommend the intervention
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention
Type of recommendation, adults aged ≥60 years*
We do not recommend the intervention
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention
*Minority opinion: shared clinical decision -making for individual adults aged 60– 64 years
Minority opinion 72

 Evidence to Recommendations Framework
Summary: Work Group Interpretations (Pfizer RSVpreF )
73

    Evidence to Recommendations Framework
Summary: Work Group Interpretations (Pfizer RSVpreF )
Among adults aged ≥65 years: Minority opinion
Balance of
consequences Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably
outweigh
desirable
consequences in
most settings The balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
consequences
probably
outweigh
undesirable
consequences in
most settings Desirable
consequences
clearly outweigh
undesirable
consequences in
most settings There is
insufficient
evidence to
determine the
balance of
consequences
Among adults aged ≥60 years:
Balance of
consequences Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably
outweigh
desirable
consequences in
most settings The balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
consequences
probably
outweigh
undesirable
consequences in
most settings Desirable
consequences
clearly outweigh
undesirable
consequences in
most settings There is
insufficient
evidence to
determine the
balance of
consequences
74

      Evidence to Recommendations Framework
Summary: Work Group Interpretations (Pfizer RSVpreF )
Type of recommendation, adults aged ≥65 years
We do not recommend the intervention
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention
Type of recommendation, adults aged ≥60 years*
We do not recommend the intervention
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention
*Minority opinion: shared clinical decision -making for individual adults aged 60– 64 years
Minority opinion 75
 Acknowledgements
 Doug Campos -Outcalt
 Katherine Fleming-Dutra
 Monica Godfrey
 Fiona Havers
 Anne Hause
 Jefferson Jones
 Megan Lindley
 Meredith McMorrow
 Rebecca Morgan
 Neil Murthy
 Sara Oliver
 Christine Olson
 Ismael Ortega Sanchez  David Shay
 Amanda Payne
 Huong Pham
 Jamison Pike
 Tamara Pilishvili
 Mila Prill
 Lauren Roper
 Diya Surie
 Christopher Taylor
 Evelyn Twentyman
 Megan Wallace
 Michael Whitaker
 Patricia Wodi 76

 Policy questions for ACIP
Should vaccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1
dose IM), rather than no vaccine, be recommended in persons aged ≥65 years?
Should vaccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1
dose IM), rather than no vaccine, be recommended in persons aged ≥60 years?
Should vaccination with Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM),
rather than no vaccine, be recommended in persons aged ≥65 years?
Should vaccination with Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM),
rather than no vaccine, be recommended in persons aged ≥60 years?

   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.

Summary: Centers for Disease Control and Prevention  Evidence to  Recommendations Framework  Respiratory  Syncytial Virus (RSV) in  Adults  GSK adjuvanted RSVpreF3 vaccine in older adults  Pfizer bivalent RSVpreF vaccine in older adults  Michael Melgar, MD  Lead, Adult RSV ACIP Work Group ACIP Meeting February 23, 2023                           Evidence to Recommendations (EtR ) Framework Poli cy Questions  Should vaccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1  dose IM),…


RSV Adults 05 Melgar 508

•
•
•
•

   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.


Chikungunya 01 Bell 508

CHIKUNGUNYA VACCINES
Beth Bell, MD, MPH
Chair, ACIP Chikungunya Vaccines Work GroupACIP Meeting
February 23, 2023
Background
Valneva completed submission of Biologics License Application (BLA) for
their chikungunya vaccine to FDA in December 2022
No chikungunya vaccine ever licensed in United States or globally
No existing ACIP chikungunya vaccine recommendations
Chikungunya Vaccines Work Group formed in May 2022 to develop policy options for ACIP’s consideration for use of chikungunya vaccine among U.S.
persons at risk of chikungunya, including
–Travelers
–Residents of U.S. territories and states with, or at risk of, transmission
–Laboratory workers
Terms of Reference for Chikungunya Vaccines Work Group
To review information on chikungunya disease, including outcomes
To review data on chikungunya epidemiology and burden among U.S. residents,
including travelers and persons living in areas at risk for local transmission
To review data on safety, immunogenicity, and effectiveness of chikungunya
vaccines
To provide evidence -based recommendation options for ACIP
To identify areas in need of further research for informing potential future vaccine recommendations
To publish a chikungunya vaccine MMWR Recommendations and Reports document
ACIP Ex Officio Invited Consultants
Beth Bell, Univ Washington (Chair) Robin Levis, FDA Alan Barrett, Univ Texas Galveston
Wilbur Chen, Univ Maryland Sixun Yang, FDA Carina Blackmore, Florida Dept Health
Lesley Dupuy, NIH Alan Lam, DoD
CDC Leads Margaret Ryan, DoD
Susan Hills, DVBD (Lead) ACIP Liaisons Steven Schofield, CATMAT
Nicole Lindsey, DVBD (Deputy Lead) Paschal Apanga, AIM David Shlim, Jackson Hole Travel & Trop Med
Elizabeth Barnett, ISTM Nestor Sosa, Uni New Mexico Hospital
James Campbell, AAP Sanet Torres, San Jorge Children & Women's Hospital
Mary Pat Friedlander, AAFP Kirsten Vannice, Bill & Melinda Gates Foundation
Mary Wilson, Univ California San FranciscoChikungunya Vaccines Work Group members
DVBD DGMQ ISD
Erin Staples Sarah Guagliardo Elisabeth Velazque z
Ann Powers
Laura Adams DHQP GRADE/ETR consultants
Joshua Wong Michael McNeil Doug Campos -Outcalt
Rebecca Morgan
NCEZID GID
Rita Helfand Rebecca Casey ACIP Secretariat
Jessica MacNeil, NCIRD
Leslie Lee, NCIRDChikungunya Vaccines Work Group CDC participants
Recap of previous Work Group presentations to ACIP
October 2022
–Overview of chikungunya virus disease and vaccines
–Immunogenicity and safety of Valneva’s chikungunya vaccine
Overview of today’s session
Global epidemiology of chikungunya
–Dr. Susan Hills (CDC/NCEZID)
Chikungunya in U.S. travelers
–Ms. Nicole Lindsey (CDC/NCEZID)
Persistent arthralgia following chikungunya
–Ms. Nicole Lindsey (CDC/NCEZID)
Work Group considerations
–Ms. Nicole Lindsey (CDC/NCEZID)

Summary: CHIKUNGUNYA VACCINES Beth Bell, MD, MPH Chair, ACIP Chikungunya Vaccines Work GroupACIP Meeting February 23, 2023 Background Valneva completed submission of Biologics License Application (BLA) for  their chikungunya vaccine to FDA in December 2022 No chikungunya vaccine ever licensed in United States or globally No existing ACIP chikungunya vaccine recommendations Chikungunya Vaccines Work Group formed in May 2022 to develop policy options for ACIP’s consideration for use of chikungunya…


Chikungunya 02 Hills 508

National Center for Emerging and Zoonotic Infectious Diseases
GLOBAL EPIDEMIOLOGY OF
CHIKUNGUNYA
Susan Hills, MBBS, MTH
CDC Lead , Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Division of Vector -Borne Diseases
Fort Collins, Colorado
ACIP meeting, February 23, 2023
Chikungunya
Mosquito -b orne viral disease
–Primarily human -mo squito -human transmission
–Mainly A edes aegypti and Aedes albopictus
Clinically characterized by acute onset of fever and
oft
en severe polyarthralgia
Risk factors for severe disease
–Age >65 years
–Underlying medical conditions
–Neonate infected through intrapartum transmission
Source: PAHO, 2011. www.paho.org
Spread of chikungunya virus into new regions, 2004 -2015
Zeller et al, Int J Infect Dis, 2016
Spread of chikungunya virus into new regions, 2004 -2015
Zeller et al, Int J Infect Dis, 2016
Chikungunya cases reported in the Americas, 2013 -2022
02000004000006000008000001000000
2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
Countries and territories with past or current
transmission of chikungunya virus, 2023
https://www.cdc.gov/chikungunya/geo/index.html

Limited data sources for understanding current
patterns of chikungunya virus transmission
WHO
websites
Ministry of
Health websites
Cases among
travelers
General features of chikungunya virus transmission
Occurs in tropical and subtropical regions
–Rare outbreaks in temperate areas
Often seen in areas with similar vector- borne diseases (e.g., dengue, Zika)
Transmission impacted by several factors including weather, environmental
factors, pre -existing population immunity, population density, local vectors
Patterns for chikungunya virus transmission vary
Ongoing low -level transmission with periodic outbreak activity in Africa,
Asia, Central America, and South America
–Immunologically susceptible individuals continue to acquire infection and
propagate human -mosquito -human cycles
–Outbreaks are unpredictable in terms of timing and size
Cessation of transmission after outbreaks is common in island nations
–Apparent interruption in Pacific Island and most of Caribbean countries and territories
–Risk for reintroduction will increase over time as population immunity decreases
Features of chikungunya outbreaks
More likely in regions
with no
 or mild
outbreaks in recent past
Can be localized or w
idespreadOften rapid increase in size
30%– 6 0% population infected within few months
Huge outbreaks, like 2014 –
2
016 in Americas, unlikely in
future
Continued reporting of large o
utbreaks likelyMany commence during tr
opical rainy season
Can occur in dry season
Period of intense tr
ansmission typically
short, often 3 –6 months
Interval between outbreaks
Unpredictable and variable, can be >20 years
Related to factors including pre -existing population immunity, build -up
of non -immune population, environmental factors
Some countries report outbreaks regularly, but typically in different
locations
Summary
Mainly tropical and subtropical areas
Currently, most countries with chikungunya virus activity have low -level
transmission
Outbreak- prone disease
Important impact when outbreaks occur as often intense, although
generally short -lived, transmission

Summary: National Center for Emerging and Zoonotic Infectious Diseases GLOBAL EPIDEMIOLOGY OF  CHIKUNGUNYA Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado ACIP meeting, February 23, 2023 Chikungunya Mosquito -b orne viral disease –Primarily human -mo squito -human transmission –Mainly A edes aegypti and Aedes albopictus Clinically characterized by acute onset of fever and  oft en severe…


Chikungunya 03 Lindsey 508

National Center for Emerging and Zoonotic Infectious Diseases
Chikungunya in US travelers
Nicole Lindsey, MS
CDC Deputy Lead , Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Centers for Disease Control and Prevention
National surveillance data for chikungunya virus disease
in US travelers
Data presented include confirmed and probable cases in residents of US
states reported to CDC (excludes US territories and associated states)
Prior to 2006, very rarely identified in US travelers; data are included from 2006– 2021
–Not nationally -notifiable from 2006 –2014
From 2006– 2021, 4,590 cases in US travelers reported to CDC
Chikungunya virus disease cases in US travelers,
2006 –2021 (N=4,590)
9 13 0 2 11 1 2 162,831
923
250156 116192
32 36
05001,0001,5002,0002,5003,000
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021Number of cases
Sex of travel- associated chikungunya cases,
2006 –2021 (N=4,590)
Sex No. (%)
Male 1,614 (35%)
Female 2,973 (65%)
3 cases unreported sex
Age of travel- associated chikungunya cases,
2006 –2021 (N=4,590)
Years No. (%)
0–19 445 (10%)
20–39 1,166 (25%)
40–59 1,927 (42%)
60–79 952 (21%)
80+ 86 (2%)
14 cases unreported age
Month of onset of travel- associated chikungunya cases,
2006 –2021 (N=4,590)
0100200300400500600700800900
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov DecNumber of cases
Month of illness onset
Month of onset of travel- associated chikungunya cases,
2006 –2021 (N=4,590)
0100200300400500600
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov DecNumber of cases
Month of illness onset2014
All other years
Outcomes of travel- associated chikungunya
cases, 2006 –2021 (N=4,590)
Outcome No. (%)
Hospitalized 834 (18%)
Died* 4(0.1%)
*Cause of death unknown: All aged 63 –84 years and died 36 –61 days after illness onset
Hospitalization rates by age among travel- associated
chikungunya cases, 2006 –2021 (N=4,590)
14 cases unreported ageAge (years) No. Hospitalized (%)
0–1 17 7(41%)
2–9 101 31 (31%)
10–19 327 60 (18%)
20–39 1,166 192 (16%)
40–59 1,927 295 (15%)
60–79 952 220 (23%)
80+ 86 33 (38%)
Regions of probable acquisition of travel- associated
chikungunya, 2006 –2021 (N=4,590)
95 cases unknown location of infection2,4946705663542936156
0 500 1,000 1,500 2,000 2,500 3,000CaribbeanCentral AmericaAsiaSouth AmericaNorth AmericaAfricaOceania/Pacific
Number of cases
Regions of probable acquisition of travel- associated
chikungunya, 2017 –2021 (N=532)
25cases unknown location of infection44253174333423
0 50 100 150 200 250 300 350CaribbeanCentral AmericaAsiaSouth AmericaNorth AmericaAfricaOceania/Pacific
Number of cases
Most common locations of probable acquisition of
travel -associated chikungunya, 2006 –2021 (N=4,590)
95 cases unknown location of infection1,01649946039729326625914213596
0 200 400 600 800 1,000 1,200Dominican RepublicPuerto RicoHaitiIndiaMexicoJamaicaEl SalvadorGuatemalaNicaraguaHonduras
Most common locations of probable acquisition of
travel -associated chikungunya, 2017 –2021 (N=532)
25cases unknown location of infection199333328242311109
0 50 100 150 200 250IndiaBangladeshMexicoBrazilPhilippinesThailandPakistanPuerto RicoMyanmar
Limitations of national surveillance data
Reported cases likely underestimate true incidence of chikungunya
disease among travelers
Reported cases likely represent higher proportion of severe outcomes
Complete data often unavailable, particularly for travel history
–No information on duration of travel or activities during travel
No information on duration of symptoms or long -term sequalae
Summary
Relatively few traveler cases reported annually except during time of large
outbreaks in Americas
Reported cases likely underestimate true incidence but overestimate proportions of severe outcomes
Very young children and older adults have highest hospitalization rates
Cases have occurred among travelers to all regions with chikungunya risk and can occur year -round
–Case numbers reflect level of chikungunya virus activity in, and number of
travelers to, destinations with risk

Summary: National Center for Emerging and Zoonotic Infectious Diseases Chikungunya in US travelers Nicole Lindsey, MS CDC Deputy Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Centers for Disease Control and Prevention National surveillance data for chikungunya virus disease  in US travelers Data presented include confirmed and probable cases in residents of US  states reported to CDC (excludes US territories and associated states)  Prior to 2006, very rarely identified in US…


Chikungunya 04 Lindsey 508

National Center for Emerging and Zoonotic Infectious Diseases
Chronic arthralgia after chikungunya
Nicole Lindsey, MS
CDC Deputy Lead , Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Centers for Disease Control and Prevention
Clinical outcomes of chikungunya virus disease
Acute symptoms typically resolve in 7 -10 days
Mortality is very rare
Significant proportion of patients have continued or recurrent arthralgia in
months and years following acute illness
Additional long- term complications reported less frequently
–Fatigue
–Depression
–Alopecia−Impaired memory
−Sleep disorders
−Lowered quality of life
Chronic joint symptoms after chikungunya
Many published studies with high variability in results based on:
–Study methodology
–Definitions and ascertainment of symptoms
–Duration of follow up
–Characteristics of patient cohort (e.g., location, demographics)
Previous meta -analyses with varying outcomes and inclusion criteria
–None used outcome and criteria most of interest to guide vaccine
recommendation process
Systematic review and meta -analysis
Objective to estimate percentage of patients with chronic arthralgia (≥3
months) following chikungunya virus infection
Literature search for articles published Jan 1, 2000 –Oct 24, 2022,
describing primary data on arthralgia following chikungunya infection
Excluded articles:
–Without laboratory confirmation of all infections
–Specific subgroups (e.g., children, people with co -infections, large
proportion of cases hospitalized for acute disease)
–Non -English language
Study selection process
1,167•
•
••••Articles identified through search. All ab stracts reviewed1,087 did not meet criteria and were excluded
80Articles with a full text review53 did not meet criteria and were excluded
27Articles met inclusion criteriaS tandardized data extraction into spreadsheet tool
Characteristics of 27 included studies (N=4,079)
Most clustered in 1 of 2 time periods (2005– 2006 and 2014– 2015)
23 communities with outbreaks, 4 travelers to outbreak locations
14 locations in Americas, 8 Indian Ocean, 4 Asia, 1 Europe
4 studies included control group of non- infected persons
Range of severity of illnesses (0 –33% hospitalized)
Varied demographics of included participants
Chronic arthralgia following chikungunya virus disease*
0%10%20%30%40%50%60%70%80%90%100%
0 3 6 9 12 15 18 21 24 27 30 33 36Percentage with chronic arthralgia
Months after illness onset
*Some studies estimated proportion with chronic arthralgia at >1 time point
Chronic arthralgia following chikungunya virus disease*
0%10%20%30%40%50%60%70%80%90%100%
0 3 6 9 12 15 18 21 24 27 30 33 36Percentage with chronic arthralgia
Months after illness onset
*Some studies estimated proportion with chronic arthralgia at >1 time point
7 studies included accounting for a total of 733 patients
All included patients who sought healthcare
Two traveler cohorts and five cohorts from communities with outbreaks
–Travelers to countries in Indian Ocean and Americas
–Outbreaks: Brazil, French Guiana, Martinique, Sint Maarten, Thailand
Predominance of females (range 52– 74%)
Range of study mean/median ages (35– 51 years)
Range of severity (hospitalization range 0 –17%)Arthralgia 3 months after chikungunya infection
Arthralgia 3 months after chikungunya infection (N=7)
Study Location Sample Rate (95% CI )
Bocanegra 2016 Travelers to the Americas, 2014 -2015 34 50% (33, 67)
Simon 2007 Travelers to the Indian Ocean, 2005 -2006 47 86% (75, 95)
Bertolotti 2020 Martinique, 2014 167 55% (48, 62)
Benjamanukul 2021 Thailand, 2018 164 53% (46, 60)
Peters 2018 Sint Marteen, 2014 56 52% (39, 64)
Silva 2021 Brazil, 2014 -2016 153 43% (36, 50)
Bonifay 2018 French Guiana, 2014 112 42% (33, 51)
Summary estimate* 51% (44, 58)
0 20 40 60 80 100
*Random effects model
Arthralgia 6 months after chikungunya infection
9 studies included accounting for a total of 961 patients
All included patients who sought healthcare
Three traveler cohorts and six cohorts from communities with outbreaks
–Travelers to countries in Indian Ocean
–Outbreaks: Bangladesh, French Guiana, Martinique, Mexico,
Suriname, Thailand
Predominance of females (range 52– 68%)
Range of study mean/median ages (32– 60 years)
Range of severity (hospitalization range 0 –33%)
Arthralgia 6 months after chikungunya infection (N=9)
Study Location Sample Rate (95% CI )
Schilte 2013 Reunion Island, 2005 -2006 180 70% (63, 77)
Simon 2007 Travelers to Indian Ocean, 2005 -2006 47 48% (35, 63)
Feldstein 2017 USVI, 2014- 2015 165 44% (37, 52)
Murillo -Zamora 2017 Mexico, 2015 136 42% (34, 50)
Bertolotti 2020 Martinique, 2014 167 36% (29, 43)
Bonifay 2018 French Guiana, 2014 112 31% (23, 40)
van Genderen 2016 Suriname, 2013 90 22% (14, 31)
Taubitz 2007 Travelers to Indian Ocean, 2006 16 13% (0, 29)
Anwar 2020 Bangladesh, 2017 48 13% (0, 22)
Summary estimate* 35% (24, 47)
*Random effects model 0 20 40 60 80 100
Arthralgia 12 months after chikungunya infection
10 studies included accounting for a total of 1,539 patients
9 included patients who sought healthcare; 1 population- based sample
All cohorts from communities with outbreaks: Aruba, Bangladesh, Brazil,
Grenada, Italy, Malaysia, Martinique, Reunion Island, US Virgin Islands (2)
Predominance of females (range 52– 73%)
Range of study mean/median ages (33– 60 years)
Range of severity (hospitalization range 0 –23%)
Arthralgia 12 months after chikungunya infection (N=10)
*Random effects modelStudy Location Sample Rate (95% CI )
de Moraes 2020 Brazil, 2016 -2018 107 61% (52, 70)
Moro 2012 Italy, 2007 250 61% (55, 67)
Schilte 2013 Reunion Island, 2005 -2006 180 58% (51, 65)
Heath 2018 Grenada, 2014 240 35% (29, 41)
Feldstein 2017 USVI, 2014- 2015 165 33% (26, 40)
Bertolotti 2020 Martinique, 2014 167 31% (24, 38)
Hennessey 2018 USVI, 2014- 2015 171 31% (24, 38)
Huits 2018 Aruba, 2014 171 26% (19, 32)
Mohd Zim 2013 Malaysia, 2008 40 23% (10, 35)
Anwar 2020 Bangladesh, 2017 48 19% (8, 30)
Summary estimate* 38% (29, 46)
0 20 40 60 80 100
Chronic arthralgia following chikungunya virus disease*
*Among 9 studies that estimated proportion with chronic arthralgia at >1 time point0%10%20%30%40%50%60%70%80%90%100%
0 3 6 9 12 15 18 21 24 27 30 33 36
Chronic arthralgia estimates among travelers (N=4)
Reference Location, Year N Population description 3m 6m 24m
Simon 2007 Indian Ocean, 2005 -2006 47French travelers treated at
Lavaren Hospital in Marseilles 86% 48%
Larrieu 2010 Indian Ocean, 2005 -2006 29French travelers treated at
University Hospital in Bordeaux 59%
Taubitz 2007 Indian Ocean, 2006 16German travelers treated at Institute of Trop Med in Hamburg 13%
Bocanegra 2016 Americas, 2014- 2015 34Spanish travelers who presented to public health 50%
Limitations
Variability in case definitions, populations included, findings
Almost all persons who seek healthcare for symptoms; not representative
of all cases
Very few studies included control group to account for background rates of arthralgia in population
–Crude estimates from all studies used to calculate summary estimates
Chronic arthralgia in controlled studies
Soumahoro 2009 ( Reunion 2005- 2006)
–199 CHIKV+,  199 CHIKV-
–At 17m, CHIKV+ more joint pain than CHIKV -(53% vs 28%)
–Estimated 47% (95% CI 37% –55%) of pain in case -patients attributed to CHIK
Gerardin 2011 ( Reunion 2005- 2006)
–512 CHIKV+, 582 CHIKV-
–At 16m, CHIKV+ more likely to complain of musculoskeletal pain (43% vs 17%)
–Estimated 60% (95% CI 52% -68%) of pain in case -patients attributed to CHIK
Chronic arthralgia in controlled studies (cont.)
Feldstein 2017 ( USVI 2014- 2015)
–165 CHIKV+, 167 CHIKV-
–At 6m, difference in arthralgia between case -patients and controls 32% (95%
CI 24% –40%) after adjusting for age, sex, history of arthritis
–At 12m, adjusted difference was 19% (95% CI 11% –28%)
Hennessey 2018 (USVI 2014- 2015)
–171 CHIKV+, 338 CHIKV-
–At 12m, 31% case -patients, 26% of controls joint pain in last week
–Estimated 23% (95% CI 9% -37%) of continued joint pain in case -patients
attributed to CHIK infection
Review of key points
A substantial proportion of patients who seek care for their acute illness have
chronic arthralgia following chikungunya virus infection
–Estimated ~one -half have arthralgia at 3 months
–Rates decrease and ~one -third estimated with arthralgia at 12 months
All proportions likely overestimates of chronic arthralgia in patients overall as
studies:
–Almost exclusively included persons who sought health care (i.e., likely more severe disease)
–Do not account for background rate of arthralgia in population
Summary
Difficult to provide precise estimate of incidence of long- term joint pain
after chikungunya
Percentages with long -term joint pain likely variable based on severity of
acute illness, age, sex, comorbidities
Long -term joint pain important complication of chikungunya that could be
prevented by vaccination

Summary: National Center for Emerging and Zoonotic Infectious Diseases Chronic arthralgia after chikungunya Nicole Lindsey, MS CDC Deputy Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Centers for Disease Control and Prevention Clinical outcomes of chikungunya virus disease Acute symptoms typically resolve in 7 -10 days Mortality is very rare Significant proportion of patients have continued or recurrent arthralgia in  months and years following acute illness Additional long- term…


Chikungunya 05 Lindsey 508

National Center for Emerging and Zoonotic Infectious Diseases
WORK GROUP PLANS AND TIMELINES
Nicole Lindsey, MS
CDC Deputy Lead , Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Centers for Disease Control and Prevention
ACIP meeting
February 23, 2023
Work Group timeline (tentative)
Dec Jan Feb Mar Apr May Jun Jul Aug Sept Oct Nov Dec Jan Feb Mar Apr2024
(Today) Global
epidemiology, US traveler, and chronic arthralgia dataPresent EtR to
ACIPPresent to ACIP            other data relevant to recommendations ACIP vote on vaccine recommendations for adult travelers and laboratory workersBLA
submission completed2023
FDA determination on priority review Possible licensure

Summary of Work Group plans and activities
Comprehensive review of immunogenicity and safety data (GRADE)
Future presentations to ACIP on topics relevant to consideration of vaccine
use in U.S. territories and states with risk of transmission
Over longer term, additional vaccine data in younger age groups and/or additional chikungunya vaccines
Thank you

Summary: National Center for Emerging and Zoonotic Infectious Diseases WORK GROUP PLANS AND TIMELINES Nicole Lindsey, MS CDC Deputy Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Centers for Disease Control and Prevention ACIP meeting February 23, 2023 Work Group timeline (tentative) Dec Jan Feb Mar Apr May Jun Jul Aug Sept Oct Nov Dec Jan Feb Mar Apr2024 (Today) Global     epidemiology, US traveler, and chronic arthralgia dataPresent EtR to  ACIPPresent to ACIP            other data…


Dengue 01 Chen 508

AA ACC CII IPP PDD Dee enn ngg guu uee eVV Vaa acc ccc cii inn nee e
WW Woo orr rkk kgg grr roo ouu upp pACIP Dengue Vaccine
Workgroup
Wilbur Chen, MD, MSc
ACIP Member and Workgroup Chair
Advisory Committee on Immunization Practices
ACIP Meeting February 23, 2023

   Dengue Virus
 DENV-1, 2, 3, 4
• Lifelong DENV type-specific
immunity
• Short-term cross-immunity (~1–2 years)
• A second dengue infection is the most important risk factor for severe dengue
 Dengue is the most common
mosquito-borne virus globally

    Dengvaxia™
an d previou  s
dengue
infection Clinical trials found different outcomes after
Dengvaxia™ vaccination among children with and
without previous dengue infection.
• Children without previous dengue infection had a
higher risk hospitalization and severe dengue if they
were vaccinated and then had a DENV infection.
• Children with previous dengue infection were
protected from hospitalization and severe dengue if
they were vaccinated with Dengvaxia™.

   Dengvaxia™ ACIP Recommendation June 2021
Three doses of Dengvaxia are indicated
for the prevention of dengue disease
caused by dengue virus serotypes 1, 2,
3, and 4 in people 9–16 years old with:
• laboratory confirmation of previous
dengue virus infection
AND
• living in endemic areas.

  Work group timeline 2023 for TAK003
Presentations to ACIP
Feb March April May June July Aug Sept Oct Nov
Vaccine efficacy, immunogenicity, and
safety data and WG Interpretation GRADE analysis and cost -
effectiveness analysis EtR, draft recommendations,
and ACIP vote

      Summary of work group plans and activities
• Review of efficacy, immunogenicity, and safety data (GRADE)
• Review of EtR domains and cost-effectiveness analysis
• Presentation of policy options and ACIP vote

     Presentations today
TAK-003 Efficacy, Safety and Immunogenicity Data
Dr. Shibadas Biswal, Takeda
Work Group Summary and Interpretation of TAK-
003 Efficacy, Safety, and Immunogenicity Data
Dr. Gabriela Paz-Bailey, CDC, NCEZID, DVBD

 AA ACC CII IPP PDD Dee enn ngg guu uee eVV Vaa acc ccc cii inn nee ess sWW Woo orr rkk kgg grr roo ouu upp p ACIP Dengue Vaccines Workgroup
ACIP Members
Wilbur Chen (Chair)
Kathy Poehling
Beth Bell
Veronica McNally
CDC Co-Lead
Gabriela Paz-Bailey Laura Adams
Ex Officio Members
Kaitlyn Morabito (NIH)
Ralph LeBlanc (FDA)
Ihid Carneiro Leao (FDA)
Kirk Prutzman (FDA) Srihari Seshadri (DOD) Liaison Representatives Elizabeth Barnett (AAP)
Rob Schechter (AIM)
Consultants
Edwin Asturias Robert Atmar
Alan Barrett
Iris Cardona
Anna Durbin
Tony Marfin Kristen Pierce
Anita Shet CDC Contributors
Josh Wong
Mimi Eckert
Rachel Eidex
Alfonso Hernandez
Susan Hills Terri Hyde
Mike McNeil
Jorge Munoz
Erin Staples
Cindy Weinbaum Rita Helfand

Summary: AA ACC CII IPP PDD Dee enn ngg guu uee eVV Vaa acc ccc cii inn nee e WW Woo orr rkk kgg grr roo ouu upp pACIP Dengue Vaccine  Workgroup  Wilbur Chen, MD, MSc  ACIP Member and Workgroup Chair  Advisory Committee on Immunization Practices  ACIP Meeting February 23, 2023                                       Dengue Virus   DENV-1, 2, 3, 4  • Lifelong DENV type-specific  immunity  • Short-term cross-immunity (~1–2 years)  • A second dengue infection is the most important risk factor for severe…


03 COVID Wallace 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.
COVID -19 Vaccine Policy and Next Steps
October 26, 2023
Megan Wallace, DrPH, MPH
COVID -19 Epidemiology
3Trends in weighted variant proportion estimates and Nowcast –
United States, June 25 –October 14, 2023
PI=Prediction Interval
Source: https://covid.cdc.gov/covid -data -tracker/#variant -proportions

Weekly population -based rates of COVID -19-associated hospitalizations by
season–COVID -NET, United States, March 2020 –September 2023
Source: Coronavirus Disease 2019 (COVID -19) Hospitalization Surveillance Network (COVID -NET); https://www.cdc.gov/coronavirus/2019 -
ncov/covidnetdashboard/de/powerbi/dashboard.html . Accessed October 16, 2023.
Oct Nov Dec Jan Feb Mar Apr May June July Aug SepHospitalizations per 100,000
010203040
Surveillance Month
2020 -20212019 -2020
2021 -2022
2022 -2023
4
5Weekly population -based rates of COVID -19-associated hospitalizations by
age group –COVID -NET , United States, October 2022 –September 2023
Source: Coronavirus Disease 2019 (COVID -19) Hospitalization Surveillance Network (COVID -NET); https://www.cdc.gov/coronavirus/2019 -
ncov/covidnetdashboard/de/powerbi/dashboard.html . Accessed October 16, 2023.
Oct Nov Dec Jan Feb Mar Apr May June July Aug Sep
Surveillance MonthHospitalizations per 100,000
010203060
50
405-17 years0-4 years
18-49 years
50-64 years
≥65 years

6Weekly COVID -19 new hospital admissions –National Healthcare Safety
Network (NHSN), United States, August 2020 –September 2023
Source: COVID -19–associated hospitalization data reported to CDC’s National Healthcare Safety Network (NHSN).
https://covid.cdc.gov/covid -data -tracker/#trends_weeklyhospitaladmissions_select_00

7Weekly provisional COVID -19 deaths  –National Vital Statistics System
(NVSS), United States January 2020 –September 2023
Source : Provisional Deaths from the CDC’s National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS). htt ps://covid.cdc.gov/covid -data -tracker/#trends_weeklydeaths_weeklydeathrateaa_00
Data during recent periods are incomplete because of the lag in time between when a death occurs and when a death certificate iscompleted, submitted to NCHS, and processed for reporting. This delay can range
from 1 week to 8 weeks or more, depending on the jurisdiction. The most recent 3 weeks of mortality counts are shaded grey be cause NVSS reporting is <95% during this period.

COVID -19 Vaccine Policy
▪ACIP met September 12, 2023 to review the available evidence for
updated COVID -19 vaccines (monovalent, XBB.1.5 component)
▪ACIP recommended updated COVID -19 vaccines as authorized under EUA
or approved by BLA in persons aged ≥6 months
–Moderna COVID -19 vaccine in persons ≥6 months
–Pfizer -BioNTech COVID -19 vaccine in persons ≥6 months
–Novavax COVID -19 vaccine in persons ≥ 12 years
▪All anticipated updated (2023 –2024 Formula) vaccines are now
authorized or approvedCOVID -19 Vaccine Policy
9
▪All doses should be homologous (i.e., from the same manufacturer)
▪All Moderna doses in ages 6 months –11 years are now 25 µcg Recommendations for children aged 6 months –4 years without
immunocompromise
Doses recommended:
▪Initial series of 2 Moderna vaccine doses OR 3 Pfizer -
BioNTech vaccine doses
▪Including a t least 1 dose of 2023 –2024 COVID -19 vaccine
10
Recommended 2023 –2024 COVID -19 mRNA vaccines for people who are NOT
immunocompromised, aged 6 months –4 years*†
*For information about administration intervals and children who transition from age 4 years to age 5 years, see Table 1 in t he Interim Clinical Considerations for
Use of COVID -19 Vaccines
† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for people
ages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccine doses ; and for people ages 18
years and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax vaccine do ses.
11
▪Exceptional situations: In the following exceptional situations , a different age -
appropriate COVID -19 vaccine may be administered:
–Same vaccine not available
–Previous dose unknown
–Person would otherwise not complete the vaccination series
–Person starts but unable to complete a vaccination series with the same COVID -19
vaccine due to a contraindication
▪AVaccine Adverse Event Reporting System (VAERS) report is not indicated for these
exceptional situations.Prior Version of Interim Clinical Considerations on
Interchangeability of COVID -19 vaccines
Clinical Guidance for COVID -19 Vaccination | CDC12
▪COVID -19 vaccine doses from the same manufacturer should be administered
whenever recommended. In the following circumstances , an age -appropriate COVID -19
vaccine from a different manufacturer may be administered:
–Same vaccine not available at the vaccination site at the time of the clinic visit
–Previous dose unknown
–Person would otherwise not receive a recommended vaccine dose
–Person starts but unable to complete a vaccination series with the same COVID -19
vaccine due to a contraindication
▪A Vaccine Adverse Event Reporting System (VAERS) report is not indicated in these
circumstances.Updated Version of Interim Clinical Considerations on
Interchangeability of COVID -19 vaccines
13
▪Updated guidance for children who transition during the initial COVID -19 vaccination
series from age 4 years to age 5 years and children who are moderately or severely
immunocompromised and transition from age 11 years to age 12 years to receive the
age-appropriate dosage based on their age on the day of vaccinationAdditional Updates to Interim Clinical Considerations
Clinical Guidance for COVID -19 Vaccination | CDC14
Recommendations for people aged 5 years and older without
immunocompromise
Doses recommended:
•1 dose of 2023 –2024 COVID -19 vaccine
▪mRNA COVID -19 vaccines authorized or approved for ages ≥6 months and Novavax COVID -19 vaccine
authorized for ages ≥12 years
▪Unvaccinated persons receiving Novavax COVID -19 should complete a 2 -dose initial series
▪New harmonized age cutoff for recommendations for young children for Moderna and Pfizer -
BioNTech COVID -19 vaccines resulting in simplified recommendations for 5 -year -olds
▪All Moderna doses in ages 6 months –11 years are now 25 µcg
▪2023 –2024 COVID -19 vaccine dose is recommended at least 2 months after receipt of the last
COVID -19 vaccine dose
15
Recommended 2023 –2024 COVID -19 mRNA vaccines for people who are NOT
immunocompromised, aged 5 –11 years*†
*For information about administration intervals and children who transition from age 4 years to age 5 years, see Table 1 in t he Interim Clinical Considerations for
Use of COVID -19 Vaccines
† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for people
ages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccine doses ; and for people ages 18
years and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax vaccine do ses.16
Recommended COVID -19 vaccination schedule for people who are NOT moderately or
severely immunocompromised , aged ≥12 years*†
*For information about administration intervals and children who transition from age 4 years to age 5 years, see Table 1 in t he Interim Clinical Considerations for
Use of COVID -19 Vaccines
† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for people
ages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccine doses ; and for people ages 18
years and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax vaccine do ses. 17
Recommendations for people aged ≥6 months who are
moderately or severely immunocompromised
Doses recommended:
▪Initial COVID -19 vaccine series*
▪At least 1 2023 –2024 COVID -19 vaccine dose
▪May receive 1 or more additional 2023 -2024
COVID -19 vaccine doses**
*Series of 3 homologous mRNA COVID -19 vaccine doses or 2 homologous Novavax COVID -19 vaccine doses
at time of initial vaccination. This could also include a history of receipt of 1 or more doses of Novavax or
Janssen, including in combination with mRNA vaccine dose(s).
**Further additional dose(s) may be administered, informed by the clinical judgement of a healthcare
provider and personal preference and circumstances. Further additional doses should be administered at
least 2 months after the last 2023 -2024 COVID -19 vaccine dose.
18
Recommended 2023 –2024 COVID -19 vaccines for people who ARE moderately or severely
immunocompromised, aged 6 months –4 years*†
* For information about administration intervals and children who transition from age 4 years to age 5 years or age 11 years to age 12 years during an mRNA
vaccination series, and administration of additional dose(s), see Table 2 in the Interim Clinical Considerations for Use of COVID -19 Vaccines
† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for
people ages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccin e doses; and for people
ages 18 years and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax va ccine doses. 19
Recommended 2023 –2024 COVID -19 vaccines for people who ARE moderately or severely
immunocompromised, aged 5 –11 years*†
* For information about administration intervals and children who transition from age 4 years to age 5 years or age 11 years to age 12 years during an mRNA
vaccination series, and administration of additional dose(s), see Table 2 in the Interim Clinical Considerations for Use of COVID -19 Vaccines
† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for
people ages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccin e doses; and for people
ages 18 years and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax va ccine doses.
 20
Recommended COVID -19 vaccination schedule for people who ARE moderately or
severely immunocompromised , aged ≥12 years*†
* For information about administration intervals and children who transition from age 4 years to age 5 years or age 11 years to age 12 years during an mRNA
vaccination series, and administration of additional dose(s), see Table 2 in the Interim Clinical Considerations for Use of COVID -19 Vaccines
† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for
people ages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccin e doses; and for people
ages 18 years and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax va ccine doses. 21
▪Consideration of additional COVID -19 vaccine doses in older adults
–Anticipated for February 2024 ACIP meeting
–Policy discussion will occur prior to individuals reaching 6 months since their last dose
▪Preparations for future COVID -19 vaccine formula updates
–Discussions will begin atJune 2024 ACIP meeting
▪Continue to monitor vaccine effectiveness, vaccine safety, and COVID -19 epidemiology
–COVID -19 vaccine recommendations can be updated if neededUpcoming COVID -19 policy discussions
22
Acknowledgements
23▪Monica Godfrey
▪Danielle Moulia
▪Katherine Fleming -Dutra
▪Ruth Link -Gelles
▪Sarah Meyer
▪Elisha Hall
▪Susan Goldstein
▪Mary Chamberland
▪JoEllen Wolicki
▪Natalie Thornburg
▪Sierra Scarbrough
▪Aron Hall
▪Christopher Taylor
▪Fiona Havers ▪Dave Wentworth
▪Meredith McMorrow
▪COVID -NET Team
▪Coronavirus and other Respiratory Viruses Division
▪National Center for Immunization and Respiratory
Diseases
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: 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. COVID -19 Vaccine Policy and Next Steps October 26, 2023 Megan Wallace, DrPH, MPH COVID -19 Epidemiology 3Trends in weighted variant proportion estimates and Nowcast –…


01 Pneumo Kobayashi 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
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Pneumococcal Vaccines Work Group
October 2023, ACIP meeting
October 26, 2023
Miwako Kobayashi, MD, MPH
•The Pneumococcal Vaccines Work Group:
•Reviews current data on pneumococcal disease burden, and on the efficacy,
effectiveness, immunogenicity, and cost -effectiveness of pneumococcal vaccines
and assesses the strength of the evidence;
•Reviews current pneumococcal vaccine recommendations considering up -to-date
evidence; and
•Develops revised or updated policy options for pneumococcal vaccines as needed.Work Group Purpose
Advisory Committee on Immunization Practices (ACIP) Work Groups | CDC
ACIP Members
▪Katherine Poehling (Chair)
▪Sarah Long
Ex Officio Members
▪Jeffrey Kelman (CMS)
▪Lucia Lee            (FDA)
▪Tina Mongeau (FDA)
▪Uzo Chukwuma (IHS)
▪Mamodikoe Makhene (NIH)
Liaison Representatives
▪Lynn Fisher                (AAFP)
▪Mark Sawyer             (AAP/COID)
▪Jason Goldman         (ACP)▪David Nace                 (AGS/AMDA)
▪Cora Hoover               (AIM)
▪Risa Claytor                 (HRSA)
▪James McAuley         (IDSA)
▪Aleksandra Wierzbowski   (NACI)
▪Robert Hopkins    (NFID)
▪Virginia Caine            (NMA)
Consultants
▪Monica Farley           (VAMC/Emory)
▪Keith Klugman          (BMGF)
▪Arthur Reingold        (UC Berkley)
▪Lorry Rubin                 (CCMC)
▪Richard Zimmerman (U. of Pittsburgh)Pneumococcal Vaccines Work Group
Division of Bacterial Diseases
▪Diepreye Ayabina
▪Adam Cohen
▪Ryan Gierke
▪Jennifer Farrar
▪Noele Nelson
Immunization Safety Office
▪Pedro Moro
Immunization Services Division
▪Janelle King
▪Andrew Leidner
▪Liz VelazquezArctic Investigations Program
▪Marc Fischer
CDC Lead
▪Miwako Kobayashi
GRADE/ EtR consultants
▪Doug Campos -Outcalt
▪Rebecca MorganCDC Contributors and Consultants
History of ACIP Pneumococcal Vaccine Recommendations
through 2019
1984PPSV23 :Adults aged
≥65 years and
individuals with
underlying conditions
2000 2010 2019 2014 2012
PCV7 :Children PCV13 :Children
(replaced PCV7)PCV13 :Adults with
immunocompromising
conditions in addition
to PPSV23PCV13 :All adults aged
≥65 years in addition
to PPSV23PCV13 :based on SCDM
for adults aged ≥65
years; routine PPSV23
recommendation
SCDM: shared clinical decision -making
Recent ACIP Pneumococcal Vaccine Recommendations,
2021 –2023
2021 2023 2022
PCV15 :ChildrenPCV20 :Expanded
indication for adults
who previously
received PCV13
PCV20 :ChildrenPCV15 and PCV20 :
Adults who have not
received PCV or whose
vaccination history is
unknown
Multiple updates have been made to adult
pneumococcal vaccine recommendations since 2012.
▪Prior to the COVID -19 pandemic, estimated to have caused
every year1:
–≥100,000 non -invasive pneumococcal pneumonia hospitalizations
–≥30,000 invasive pneumococcal disease (IPD) cases (e.g., bacteremic pneumonia,
pneumococcal bacteremia, meningitis)
•3,000 IPD deaths
▪Preliminary data show increase in IPD cases in late 20222
–Increase in other invasive bacterial infections reported in children3,4Pneumococcal Disease Burden among U.S. Adults
1. Kobayashi M. October 20, 2021 ACIP Meeting Presentation. Considerations for Age -Based and Risk -Based Use of PCV15 and PCV20 amon g U.S. Adults and Proposed Policy
Options.
2. CDC Active Bacterial Core surveillance unpublished data
3. Notes from the Field: Update on Pediatric Intracranial Infections —19 States and the District of Columbia, January 2016 –March 2 023 | MMWR (cdc.gov)
4. Notes from the Field: Increase in Pediatric Invasive Group A Streptococcus Infections —Colorado and Minnesota, October –December 2022 | MMWR (cdc.gov)
Invasive pneumococcal disease incidence among adults aged ≥65 years
reached a historically low level early in the COVID -19 pandemic
IPD=invasive pneumococcal disease
CDC Active Bacterial Core surveillancePCV13: children
PCV13: adults
Approximately 40% of IPD cases in adults aged ≥65 years were caused
by serotypes not contained in currently recommended vaccines
CDC Active Bacterial Core surveillance
New Adult Pneumococcal Vaccines in Advanced Stages of Development
1 3 4 5 6
A6
B7
F9
V1
41
8
C1
9
A1
9
F2
3
F2
2
F3
3
F8 1
0
A1
1
A1
2
F1
5
B2 9
N1
7
F2
01
5
A1
5
C1
6
F2
3
A2
3
B2
4
F3
13
5
B
PCV15
PCV20
PPSV23
Pn-
MAPS24v20
B
VAX -2420
B
V11620
A
24-valent pneumococcal vaccines
•Completed phase 1/2 study for adults1Pn-MAPS24v, GSK
•Completed phase 1/2 studies for adults, undergoing phase 2 studies
in infants2VAX -24, Vaxcyte
21-valent pneumococcal conjugate vaccine V116, Merck
•Completed phase 1/2 study for adults3
•Phase 3 studies in adults are currently ongoing
1. Chichili et al. Vaccine 2022; 2. ClinicalTrials.gov ID: NCT05266456, NCT05297578, and NCT05844423 ; 3. Platt et al. Lancet ID 2022.
▪Review evidence on use of 21-valent pneumococcal conjugate
vaccine (V116) for adults
–Biologics License Application for V116 to the FDA is anticipated in Q4 of 2023, with
an anticipated FDA approval in the first half of 2024Next Steps for Pneumococcal Vaccines Work Group
▪Evidence to support EtR domains including,
–Epidemiology of pneumococcal disease among U.S. adults
–Assessment of pneumococcal disease caused by serotypes not included in V116 (but
included in existing vaccines)
–Phase 2/3 clinical trial data on V116 among adults
–Feasibility and resource use involved in V116 use among adults
–Health equity considerations
▪Aim to have an ACIP vote on policy options shortly after FDA
approval of V116Data to be Reviewed by Work Group
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.
Thank you!

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. Pneumococcal Vaccines Work Group October 2023, ACIP meeting October 26, 2023 Miwako Kobayashi, MD, MPH •The Pneumococcal Vaccines Work Group: •Reviews current data on…