02 Hills chikungunya 508

Evidence to Recommendations and proposed
recommendations for use of virus -like particle
chikungunya vaccine among adolescent and adult travelers
Dr Susan Hills
CDC Lead, ACIP Chikungunya Vaccines Work GroupNational Center for Emerging and Zoonotic Infectious Diseases
April 16 , 2025
Virus- like particle chikungunya vaccine
(CHIK -VLP) and its licensure
•Manufactured by Bavarian Nordic (trade name: VIMKUNYA
 )
•Licensed in United States on February 14, 2025
•Indicated for use in persons aged ≥12 years
•Single dose primary schedule CHIK -VLP

Licensure
•Licensed through Accelerated Approval pathway used for products for
serious conditions and that fill unmet medical need
-Traditional approval challenging as efficacy trial difficult when outbreaks unpredictable
and duration can be short, and no established immunologic correlate of protection
•Effectiveness demonstrated based on adequate and well -controlled trials
showing vaccine has effect on surrogate endpoint reasonably likely to
predict clinical benefit
-CHIK -VLP surrogate was chikungunya neutralizing antibody titer threshold preventing
viremia in non -human primates challenged with virus
•Regardless of licensure pathway, safety must be assessed in adequate
and well -controlled studies with appropriate safety sample size
Post -marketing study
•Under FDA regulations, post -marketing clinical trial required to confirm
clinical benefit
•Randomized, double -blind, placebo -controlled study planned to evaluate
efficacy, safety, and immunogenicity of CHIK -VLP
Evidence to Recommendations for use of
CHIK -VLP among travelers aged ≥12 years
Should CHIK- VLP be recommended for use in persons aged
≥12 years traveling to areas with risk of chikungunya virus
transmission?Policy question
EtR framework
EtR Domain Question
Public health problem •Is the problem (chikungunya) of public health importance?
Benefits and harms•How substantial are the desirable anticipated  effects of CHIK -VLP?
•How substantial are the undesirable anticipated  effects?
•Do the desirable effects outweigh the undesirable  effects?
•What is the overall certainty of this evidence for the critical outcomes?
Values•Does the target population feel the desirable effects are large relative to
the undesirable effects?
•Is there important variability in how patients value theoutcomes?
Acceptability •Is the intervention acceptable to keystakeholders?
Resource use •Is the intervention a reasonable and efficient allocation ofresources?
Equity •What would be the impact of the intervention on health equity?
Feasibility •Is the intervention feasible to implement?
Domain 1: Public Health Problem
Chikungunya virus transmission
Countries and territories with current or past transmission of chikungunya virus

Globally, ~620,000 cases
reported in 2024 but likely
underestimate
Countries and territories with current or past transmission of chikungunya virusChikungunya virus disease cases
 Outbreaks can be
large and explosive
•One-third to three -
quarters of po pulation
affected
•Substantial morbidity
•Stresses healthcare
capacity
•Fever and polyarthralgia
-Arthralgia often severe and can be
debilitating
-Multiple joints involved, most
commonly hands and feet
•Other symptoms include
headache, myalgia, fatigue, rash,
abdominal pain, and vomiting
•No anti -viral treatment
-Supportive managementImpact of acute illness
Image above from : https://www.paho.org/en/topics/chikungunya
Impact of disease: severe presentations
•Cases of severe illness uncommon
-Infection -related  (e.g., encephalitis,
myocarditis )
-Exacerbation of underlying medical
conditions
•Rare deaths
-Case fatality rate: 0.01% –0.5%
-Mostly in older adults , particularly
those with comorbidities, and young
infants  infected through intrapartum
transmission or by mosquito bites
Images from : https://www.paho.org/en/topics/chikungunya
Impact of disease: Arthralgia that persists or recurs
•Most patients have arthralgia that resolves in 7 –10 days
•Arthralgia sometimes persists or relapses with other symptoms e.g.,
fatigue
•Rates of ongoing arthralgia vary based on several factors e.g., severity of
acute illness, age, pre -existing joint problems
Impact of disease: Arthralgia that persists or recurs
51% 3 months
post -infectionAcute
illness
100%
Based on recent meta -analysis (Lindsey N. Chronic arthralgia after chikungunya. US Advisory Committee on Immunization Practices meeting, June 2023)*
Impact of disease: Arthralgia that persists or recurs
Based on recent meta -analysis (Lindsey N. Chronic arthralgia after chikungunya. US Advisory Committee on Immunization Practices meeting, June 2023)*
*Rates likely overestimated as background rate of arthralgia in the population could not be taken into account51% 3 months
post -infection12 months
post -infection
38%Acute
illness
100%
•Risk highly variable from location -to-location and from year -to-year
•2014– 2015: High case load during outbreak in the Americas
•2022– 2024: 100– 200 US traveler cases/year although extent of underdiagnosis and
underreporting unknownIs chikungunya a problem of public health importance for
US travelers?
Chikungunya cases in US travelers reported to CDC, 2012– 2024 (N=5,012)*
*2024 data are provisional

Comparison of chikungunya  vs. dengue  cases among travelers
Except during 2014– 2015, 3–18 times fewer  chikungunya  cases reported annually as dengue  cases

Chikungunya risk estimates for travelers for 1 week
travel to outbreak  or non- outbreak  area*
•Travelers to outbreak  area for 1 week
-Clinical disease: 667 cases per 100,000
-Hospitalization: 27 cases per 100,000
-Chronic arthralgia of any severity at 12 months: 253 cases per 100,000
*Based on unpublished data gathered during outbreaks in Puerto Rico and United States Virgin Islands with potential limitatio ns and calculations requiring assumptions
•Travelers to outbreak  area for 1 week
-Clinical disease: 667 cases per 100,000
-Hospitalization: 27 cases per 100,000
-Chronic arthralgia of any severity at 12 months: 253 cases per 100,000
•Travelers to non-outbreak  area for 1 week
-Clinical disease: 6.7 cases per 100,000
-Hospitalization : 0.3 cases per 100,000
-Chronic arthralgia of any severity at 12 months: 2.5 cases per 100,000
*Based on unpublished data gathered during outbreaks in Puerto Rico and United States Virgin Islands with potential limitatio ns and calculations requiring assumptionsChikungunya risk estimates for travelers for 1 week
travel to outbreak  or non- outbreak  area*
•Travelers visiting non-outbreak  area for 1 week
-Clinical disease: 6.7 cases per 100,000
-Hospitalization : 0.3 cases per 100,000
-Chronic arthralgia of any severity at 12 months: 2.5 cases per 100,000
•Travelers visiting non-outbreak  area for 6 months
-Clinical disease: 176 cases per 100,000
-Hospitalization : 7 cases per 100,000
-Chronic arthralgia of any severity at 12 months: 67 cases per 100,000
*Based on unpublished data gathered during outbreaks in Puerto Rico and United States Virgin Islands with potential limitatio ns and calculations requiring assumptionsChikungunya risk estimates for travelers to non- outbreak
area for 1 week  or 6 months*
Question: Is chikungunya of public health importance?
•For US travelers
-Most important factor is level of
chikungunya virus transmission at
destination
-Additional factors are travel duration
and other considerations (e.g., age,
underlying medical conditions)□No
□Probably no
□Probably yes
□Yes
□Varies
□Don’t know
Domain 2: Benefits and Harms of CHIK -VLP
Desirable  anticipated effects of vaccination
Critical GRADE outcomes Comment
Short -term vaccine efficacy (i.e., at 21 days)
against diseaseImmunogenicity data only
Long -term vaccine efficacy (i.e., at 12 months)
against diseaseImmunogenicity data only
•No established immunologic correlate of protection
-Surrogate marker of protection based on neutralizing antibody titer estimated from
validated non- human primate model
Seroresponse rate at 21 days after vaccination*
•Key results from two randomized controlled trials
-Adolescents and adults aged 12 –64 years (N= 2,559 subjects with results in
vaccine arm)
-Older adults aged ≥65 years (N=189 subjects with results in vaccine arm)
•Seroresponse  rate 97% overall
-98% in ages 12– 64 years vs. 87% in ages ≥65 years
*Percent of subjects with anti -chikungunya virus 80% serum neutralizing antibody titer ≥100
Seroresponse rate at 12 months after vaccination*
•Long -term results from Phase 3 study not yet available
•Results from one Phase 2 study with data collection at 11 months
-Adults aged 18 –45 years (N=46 subjects with results)
-Seroresponse rate 91%
•Given limited data, also reviewed Phase 3 study results at 6 months
-Adolescents and adults aged 12 –64 years: seroresponse rate 85% (1967/2301)
-Older adults aged ≥65 years: seroresponse rate 76% (139/184)
*Percent of subjects with anti -chikungunya virus 80% serum neutralizing antibody titer ≥100
Question: How substantial are the desirable  anticipated
effects?
□Minimal
□Small
□Moderate
□Large
□Varies
□Don’t know
Undesirable  anticipated effects of vaccination
Critical outcomes
Serious adverse events (SAEs) All SAEs and related SAEs
Arthralgia/arthritisAll arthralgia, severe arthralgia, persistent
arthralgia, and arthritis
SAEs within 6 months
•SAE
-0.9% (27 of 2,996) vaccinated subjects in 2 randomized trials
-0.6% (4 of 671) placebo recipients*
•Related SAE
-1 event (0.03%) considered possibly vaccine -related by site investigator
•Retinal detachment in subject with history of seeing black spots in same
eye 1 month pre -study#
*Not significantly different;   #Considered unrelated by Safety Monitoring Committee Chair
Arthralgia and arthritis after vaccination
•Results from 3 randomized studies
•Arthralgia within 7 days
-7% (221 of 3,019) vaccinated vs. 6% (52 of 866) placebo recipients*
•Severe arthralgia# within 7 days
-0.2%  (7 of 3,019) vaccinated vs. 0.2%  (2 of 866) placebo recipients*
•Persistent arthralgia commencing within 7 days and with duration >15 days
-0.03%  (1 of 3,019) vaccinated vs. 0% (0 of 866) placebo recipients*
•Arthritis within 28 days
-0.03%  (1 of 3,048) vaccinated vs. 0% (0 of 723) placebo recipients*
*Not significantly different; #Event that prevented daily activity in accordance with US FDA toxicity grading scale

Question: How substantial are the undesirable
anticipated effects?
•Rates of SAEs and all arthralgia/arthritis
outcomes not significantly different in vaccine and placebo groups
•Unclear determination of relatedness
for SAE reported as related□Minimal
□Small
□Moderate
□Large
□Varies
□Don’t know
Do the desirable effects outweigh the undesirable
effects?
Very good short -term seroresponse  rates and similar
rates of adverse events in vaccine and placebo groups
Can prevent acute illness that can be severe, rare
serious complications, and long -term arthralgia
Possibility of rare SAEs; with safety results from ~3,000
subjects, post -marketing safety surveillance important
Do the desirable effects outweigh the undesirable
effects?
□Favors intervention
□Favors comparison
□Favors both
□Favors neither
□Varies
□Don’t know•Risk varies substantially and inversely
with chikungunya virus transmission intensity
•Risk-benefit assessment favorable if
vaccine used in line with proposed recommendations which target higher risk travelers
Overall certainty of evidence from GRADE analysis for
critical outcome of prevention of disease
Critical outcome Certainty
of evidenceRationale
Short -term vaccine
efficacy at 21 daysLow Downgraded for very serious indirectness
•No effectiveness data, immunogenicity data used
•No established immunologic correlate of protection
•Surrogate endpoint approved for licensure has FDA
requirement for post -licensure controlled trials to
confirm clinical benefit
Overall certainty of evidence from GRADE analysis for
critical outcome of prevention of disease
Critical outcome Certainty
of evidenceRationale
Short -term vaccine
efficacy at 21 daysLow Downgraded for very serious indirectness
•No effectiveness data, immunogenicity data used
•No established immunologic correlate of protection
•Surrogate endpoint approved for licensure has FDA
requirement for post -licensure controlled trials to
confirm clinical benefit
Long -term vaccine
efficacy at 12 monthsVery low Downgraded for very serious indirectness and imprecision•Indirectness factors as above
•Results from Phase 3 trial not yet available so used
data from Phase 2 study (N=46 subjects with results)
supplemented by Phase 3 studies 6 -month data
Overall certainty of evidence from GRADE analysis for
critical outcome of prevention of disease
Critical outcome Certainty
of evidenceRationale
Short -term vaccine
efficacy at 21 daysLow Downgraded for very serious indirectness
•No effectiveness data, immunogenicity data used
•No established immunologic correlate of protection
•Surrogate endpoint approved for licensure has FDA
requirement for post -licensure controlled trials to
confirm clinical benefit
Long -term vaccine
efficacy at 12 monthsVery low Downgraded for very serious indirectness and imprecision•Indirectness factors as above
•Results from Phase 3 trial not yet available so used
data from Phase 2 study (N=46 subjects with results)
supplemented by Phase 3 studies 6 -month data
GRADE summary of certainty: Low (short -term) and very low (long -term)
Summary statements on short - and long - term
prevention of chikungunya by CHIK -VLP
•For short -term disease prevention, based on large effect and low certainty
in the evidence
-CHIK -VLP might result in large increase in short -term protection against
chikungunya
•For long -term disease prevention, based on large effect and very low
certainty in the evidence
-CHIK -VLP might result in large increase in long -term protection against
chikungunya but the evidence is very uncertain
Critical outcome Certainty
of evidenceRationale
Any or related SAEs Low Downgraded for very serious imprecision
•Fragility of estimate as sample size insufficient to
detect rare events
•95% confidence intervals (CI) for effect estimates include potential for possible benefits or harmsOverall certainty of evidence from GRADE analysis for
critical outcome of potential adverse events
Critical outcome Certainty
of evidenceRationale
Any or related SAEs Low Downgraded for very serious imprecision
•Fragility of estimate as sample size insufficient to
detect rare events
•95% confidence intervals (CI) for effect estimates include potential for possible benefits or harms
Any, severe, or
persistent arthralgia, or
arthritisModerate Downgraded for serious imprecision
•95% CI for effect estimate includes potential for
possible benefits or harms (arthralgia)
•Fragility of estimate as sample size insufficient to
detect rare events (severe or persistent arthralgia,
arthritis)Overall certainty of evidence from GRADE analysis for
critical outcome of potential adverse events
Critical outcome Certainty
of evidenceRationale
Any or related SAEs Low Downgraded for very serious imprecision
•Fragility of estimate as sample size insufficient to
detect rare events
•95% confidence intervals (CI) for effect estimates include potential for possible benefits or harms
Any, severe, or
persistent arthralgia, or
arthritisModerate Downgraded for serious imprecision
•95% CI for effect estimate includes potential for
possible benefits or harms (arthralgia)
•Fragility of estimate as sample size insufficient to
detect rare events (severe or persistent arthralgia,
arthritis)
GRADE summary of certainty: Low (based on outcome with lowest certainty level)Overall certainty of evidence from GRADE analysis for
critical outcome of potential adverse events
Summary statements on safety of CHIK -VLP
•For SAEs and related SAEs, based on small but important effect and low
certainty in the evidence
-CHIK -VLP might result in slight increase in SAEs and related SAEs when compared
with placebo
•For arthralgia/arthritis outcomes, based on no effect and moderate certainty in the evidence
-CHIK -VLP probably results in little to no difference in arthralgia, severe arthralgia,
persistent arthralgia, and arthritis after vaccination compared with placebo
Domain 3: Values and Preferences
Perceptions of US adults aged ≥18 years of chikungunya
disease and value of chikungunya vaccination
•Online CDC survey conducted in 2022
•Participants provided information on
-Risk for disease with travel during outbreak or non -outbreak periods
-Rates of chronic arthralgia after chikungunya
-Vaccine cost
N=4,14642%
26%32%
Likely* Unsure Unlikely**Perceptions of US adults aged ≥18 years of chikungunya
disease and value of chikungunya vaccination
Outbreak (disease risk of 1 in 150)
*Includes very and somewhat likely responses
**Includes very and somewhat unlikely responses
N=4,146 N=4,13842%
26%32%
Likely* Unsure Unlikely**27%
24%49%
Likely* Unsure Unlikely**Perceptions of US adults aged ≥18 years of chikungunya
disease and value of chikungunya vaccination
Outbreak (disease risk of 1 in 150) Non -outbreak (disease risk of 1 in 15,000)
*Includes very and somewhat likely responses
**Includes very and somewhat unlikely responses
Variability in responses
•Lower likelihood of vaccination
-Persons aged 18 –29 years
-Lower education
-Lower household income
-Black race
Important factors in decision -making
Risk of disease
Vaccine side effects Avoiding long -term joint pain Vaccine cost
Question: Does the target population feel that the
desirable effects of vaccination are large relative to undesirable effects?
•Level of disease risk key factor in
determining likelihood of vaccination□No
□Probably no
□Probably yes
□Yes
□Varies
□Don’t know
Question: Is there important uncertainty about or
variability in how much people value the main outcomes?
□Important uncertainty or variability
□Probably not important uncertainty
or variability
□No important uncertainty or variability
□No known undesirable outcomes
Domain 4: Acceptability
Acceptability to key stakeholders
•Travel medicine and other healthcare providers
-Vaccine is tool for disease prevention in addition to guidance for
mosquito bite prevention measures
•Travelers
-Vaccine provides option to protect from disease that can cause severe acute illness and potentially long -term joint pain
-Vaccine recommendations might allow insurance coverage
Question: Is the intervention acceptable to key
stakeholders?
□No
□Probably no
□Probably yes
□Yes
□Varies
□Don’t know
Domain 5: Resource Use
Resource use considerations
•Cost -effectiveness analysis for chikungunya vaccination of travelers has not been
published
•Past analyses conducted for travel vaccines indicate most travel vaccines are not
cost-effective
–Number of travelers needed to be vaccinated to prevent one case often high
•Resource use considerations less relevant for travel vaccine as not paid for by public
funding
•Travelers make individual decisions based on their willingness to pay and
perceptions and tolerance of risk
Question: Is the intervention a reasonable and efficient
allocation of resources?
•Vaccine recommendations targeted to
higher risk travelers so financial
implications of vaccine purchase and
most benefit will be for travelers at
highest risk of disease □No
□Probably no
□Probably yes
□Yes
□Varies
□Don’t know
Domain 6: Equity
Health equity considerations
•Vaccine paid for out of pocket by most travelers
-Some travelers will have financial means to allow vaccination and others
will not
Question: What would the impact be on health equity?
•Chikungunya vaccine
recommendations cannot address this issue□Reduced
□Probably reduced
□Probably no impact
□Probably increased
□Increased
□Varies
□Don’t know
Domain 7: Feasibility
Feasibility considerations
•Easy to administer in healthcare setting because of single dose primary schedule
•Resources to guide implementation will be available on CDC website, including
information on areas with outbreaks and with elevated risk for US travelers
-Possible challenge is need to regularly refer to website for current  information
•Delays in recognizing outbreaks could impact implementation of outbreak
recommendation and put travelers at risk
-Risk-benefit assessment does not favor vaccinating all travelers to address this issue
•Potential challenges with availability of two chikungunya vaccines with some different
indications for use, so clear information will be needed
Question: Is the option feasible to implement?
□No
□Probably no
□Probably yes
□Yes
□Varies
□Don’t know
Balance of consequences
o Undesirable
consequences clearly outweigh desirable consequences in most settingso Undesirable consequences probably outweigh desirable consequences in most settingso The balance between desirable and undesirable consequences is closely balanced or uncertaino Desirable
consequences
probably
outweigh
undesirable
consequences
in most settingso Desirable
consequences clearly outweigh undesirable consequences in most settingso There is insufficient evidence to determine the balance of consequences
Draft recommendations for CHIK -VLP for
ACIP’s consideration
Acknowledgment of ACIP Chikungunya Vaccines Work Group
members’ hard work and decision -making challenges for
finalizing vaccine recommendations
ACIP recommends  virus -like particle chikungunya vaccine for persons aged
≥12 years traveling to a country or territory where there is a chikungunya
outbreak.#
In addition, virus -like particle chikungunya vaccine may be considered  for
persons aged ≥12 years traveling or taking up residence in a country or
territory without an outbreak but with elevated risk for US travelers# if
planning travel for an extended period of time e.g., 6 months or more.Draft recommendations for CHIK -VLP
#Resources will be available on CDC website
Specifying areas with outbreaks and risk for US travelers
for purposes of recommendations
•Outbreak
-Defined as occurring when CDC posts information on outbreak on CDC website
•Country or territory without an outbreak but with elevated risk for US
travelers
-Median of ≥1 US traveler case during last 5 years with at least 1 confirmed case
based on molecular testing or presence of IgM and neutralizing antibodies*
*Excludes probable cases with IgM antibodies alone because high proportion are false positive results
ACIP recommends  virus -like particle chikungunya vaccine for persons aged
≥12 years traveling to a country or territory where there is a chikungunya
outbreak.
In addition, virus -like particle chikungunya vaccine may be considered  for
persons aged ≥12 years traveling or taking up residence in a country or
territory without an outbreak but with elevated risk for US travelers if
planning travel for an extended period of time e.g., 6 months or more.Draft recommendations for CHIK -VLP
ACIP Chikungunya Vaccines Work Group
Arboviral Diseases Branch, CDC
•Erin StaplesAcknowledgments
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: Evidence to Recommendations and proposed  recommendations for use of virus -like particle  chikungunya vaccine among adolescent and adult travelers Dr Susan Hills CDC Lead, ACIP Chikungunya Vaccines Work GroupNational Center for Emerging and Zoonotic Infectious Diseases April 16 , 2025 Virus- like particle chikungunya vaccine  (CHIK -VLP) and its licensure •Manufactured by Bavarian Nordic (trade name: VIMKUNYA  ) •Licensed in United States on February 14, 2025 •Indicated for use in persons…


03 staples chikungunya 508

Evidence to Recommendations and proposed
recommendations for use of virus -like particle
chikungunya vaccine among laboratory workers
Dr J. Erin Staples
Arboviral Diseases Branch
Centers for Disease Control and PreventionNational Center for Emerging and Zoonotic Infectious Diseases
April 16 , 2025
Infections among laboratory workers
•At least 44 chikungunya virus infections identified among laboratory
workers worldwide over ~50 years1–3
-43 cases overt disease, 1 asymptomatic infection, no deaths
•4 disease cases in US laboratorians since chikungunya became notifiable disease in 2015
•Identified cases underestimate all infections as no formal laboratory surveillance system
1. The Subcommittee on Arbovirus Laboratory Safety of the American Committee on Arthropod -Borne Viruses. Am J Trop Med Hyg  1980;
2. Rusnak JM, et al. J Occup Environ Med 2004; 3. US national arboviral disease surveillance system, 2015– 2024
Routes of transmission in the laboratory
•Aerosol
•Percutaneous
-Needlestick while working with and
injecting mice
-Forceps prick while dissecting mosquitoes infected with chikungunya virus
•Mucosal (possible)

•Three main genotypes of chikungunya virus (Asian, West African, and
East/Central/South African [ECSA])
-CHIK -VLP based on West African genotype virus, most genetically distinct
-Chikungunya virus strains generally considered to constitute single serotype
•Non -human primates (NHPs) immunized with virus -like particles were protected
from challenge with ECSA chikungunya virus strain1
-No NHP challenge studies with Asian genotype virus strain
•Sera from vaccinated persons showed neutralization of all genotypes2,3
-Some variability in neutralizing antibody titers between lineages
•CHIK -VLP will likely cross -protect against all virus strains but not provenCross- protection against different chikungunya virus genotypes
by chikungunya virus -like particle vaccine (CHIK -VLP)
1. Akahata W et al, Nat Med 2010. 2. Goo et al, J Infect Dis 2016. 3. Chang LJ et al, Lancet 2014.
Should chikungunya virus -like particle vaccine be recommended for
laboratory staff at risk for chikungunya virus infection?Policy question
Domain: Public Health Problem
Topic Decision Considerations
Public health
problemNo, not of public health importance overall•Only occasional laboratory -acquired
infections reported in United States
•For laboratorians potential exists for acute infection with severe polyarthralgia and possible chronic arthralgia
Domain: Benefits and Harms*
Topic Decision Considerations
Benefits and
HarmsDesirable anticipated effects of vaccination are moderate•Very good short -term seroresponse  rates
•Limited long -term seroresponse  data;
sustained protection important for staff if work in laboratory for many years
•CHIK -VLP likely protects against all
chikungunya virus genotypes but not proven
Undesirable anticipated effects of vaccination are small•Rates of serious adverse events and all arthralgia/arthritis outcomes not significantly different between vaccinated and placebo groups in clinical trials
*Based on GRADE assessment
Domain: Benefits and Harms*
Topic Decision Considerations
Benefits and
HarmsDesirable effects outweigh the undesirable effects (favors intervention)•Acceptable immunogenicity and safety results from clinical trials
•Prevention of potentially severe illness
Certainty of evidence for
prevention of disease: Low
(short -term efficacy) and very
low (long -term efficacy)
Certainty of evidence for
potential adverse events: Low•Review of clinical trial data in GRADE
assessment
*Based on GRADE assessment
Domain: Values
Topic Decision Considerations
Values Laboratorians likely think
desirable effects large relative to
undesirable effects
No important variability•Scientists understand risks of disease and
risks and benefits of vaccination
Acceptability Yes, acceptable to key stakeholders•Acceptable for occupational health
directors, laboratory managers, and
laboratorians because will improve safety
Domain: Acceptability
Topic Decision Considerations
Values Laboratorians likely think
desirable effects large relative to
undesirable effects
No important variability•Scientists understand risks of disease and
risks and benefits of vaccination
Acceptability Yes, acceptable to key stakeholders•Acceptable for occupational health
directors, laboratory managers, and
laboratorians because will improve safety
Domain: Resource Use
Topic Decision Considerations
Resource use Yes, reasonable and efficient
allocation of resources•Vaccination for limited number of staff undertaking research or specific diagnostic work with chikungunya virus
•Small cost to avoid impact and costs of worker becoming infected
Equity Probably increased •If employer offers vaccination, will improve safety for staff and addresses an
occupational health issue
Feasibility Yes, feasible •Likely incorporated into existing
occupational health program
Domain: Equity
Topic Decision Considerations
Resource use Yes, reasonable and efficient
allocation of resources•Vaccination for limited number of staff undertaking research or specific diagnostic work with chikungunya virus
•Small cost to avoid impact and costs of worker becoming infected
Equity Probably increased •If employer offers vaccination, will improve safety for staff and addresses an
occupational health issue
Feasibility Yes, feasible •Likely incorporated into existing
occupational health program
Domain: Feasibility
Topic Decision Considerations
Resource use Yes, reasonable and efficient
allocation of resources•Vaccination for limited number of staff undertaking research or specific diagnostic work with chikungunya virus
•Small cost to avoid impact and costs of worker becoming infected
Equity Probably increased •If employer offers vaccination, will improve safety for staff and addresses an
occupational health issue
Feasibility Yes, feasible •Likely incorporated into existing
occupational health program
Balance of consequences for CHIK- VLP vaccination of
laboratory workers at risk for chikungunya virus infection
o Undesirable
consequences clearly outweigh desirable consequences in most settingso Undesirable consequences probably outweigh desirable consequences in most settingso The balance between desirable and undesirable consequences is closely balanced or uncertaino Desirable
consequences
probably
outweigh
undesirable
consequences
in most settingso Desirable
consequences clearly outweigh undesirable consequences in most settingso There is insufficient evidence to determine the balance of consequences
ACIP recommends virus- like particle chikungunya vaccine for laboratory
workers with potential for exposure to chikungunya virus.*Draft recommendation for CHIK -VLP vaccination for
laboratory workers
*Consistent with language of recommendation for vaccination of laboratory workers with live attenuated
chikungunya vaccine approved by ACIP in February 2024
•Local biosafety committee should undertake risk assessment of potential
for chikungunya virus exposure considering
-Type of work to be performed
-Biosafety level at which work is being conducted
•Vaccination not necessary for workers handling routine clinical samples Information accompanying recommendations
ACIP recommends virus- like particle chikungunya vaccine for laboratory
workers with potential for exposure to chikungunya virus.Draft recommendation for CHIK -VLP vaccination for
laboratory workers
ACIP Chikungunya Vaccines Work Group
Arboviral Diseases Branch, CDC
•Susan HillsAcknowledgments
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: Evidence to Recommendations and proposed  recommendations for use of virus -like particle  chikungunya vaccine among laboratory workers Dr J. Erin Staples Arboviral Diseases Branch Centers for Disease Control and PreventionNational Center for Emerging and Zoonotic Infectious Diseases April 16 , 2025 Infections among laboratory workers  •At least 44 chikungunya virus infections identified among laboratory  workers worldwide over ~50 years1–3 -43 cases overt disease, 1 asymptomatic infection, no…


04 Hills chikungunya 508

Surveillance for adverse events following use of
live attenuated chikungunya vaccine and its use
among travelersNational Center for Emerging and Zoonotic Infectious Diseases
Dr. Susan Hills
CDC Lead, Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Division of Vector -Borne Diseases
Fort Collins, Colorado
Advisory Committee on Immunization Practices meeting
April 16 , 2025
Background on live attenuated
chikungunya vaccine
Live attenuated chikungunya vaccine (CHIK -LA)
•Manufactured by Valneva and called IXCHIQ
•Licensed in United States in November 2023 for individuals aged ≥18 years
•Single dose primary schedule
•Licensed based on immunogenicity and safety data in ~3,500 adults

Local and systemic adverse events in pivotal Phase 3 trial
•Safety data from 3,082 subjects
•Solicited local reactions  within 10 days after vaccination
-15% in vaccinees vs 11% in placebo recipients
•Solicited systemic adverse events  (AE) within 10 days after vaccination
-50% in vaccinees vs 27% in placebo recipients
-Most common were headache, fatigue and myalgia in ~25% –30% of vaccinees
Schneider M et al. Safety and immunogenicity of a single -shot live -attenuated chikungunya vaccine: a double -blind, multicentre , randomised , placebo- controlled, phase 3 trial. Lancet 2023; 401: 2138 –2147.
Comparison of adverse events in 18 –64 years and ≥65 years*
18–64 years ≥65 years
Vaccine
(n=2,736)(95% CI) Placebo
(n=916)(95% CI) Vaccine
(n=346)(95% CI) Placebo
(n=117)(95% CI)
Any related AE 52% (50%– 54%) 32% (29% –35%) 46% (41%– 52%) 26% (18% –35%)
Any related
severe AE2% (2%– 3%) 0.1% (0%–0.6%) 1% (0.3%– 3%) 0 (0%–3%)
*Data from pivotal Phase 3 trial
Comparison of adverse events in 18 –64 years and ≥65 years*
18–64 years ≥65 years
Vaccine
(n=2,736)(95% CI) Placebo
(n=916)(95% CI) Vaccine
(n=346)(95% CI) Placebo
(n=117)(95% CI)
Any related AE 52% (50%– 54%) 32% (29% –35%) 46% (41%– 52%) 26% (18% –35%)
Any related
severe AE2% (2%– 3%) 0.1% (0%–0.6%) 1% (0.3%– 3%) 0 (0%–3%)
*Data from pivotal Phase 3 trial
•Fever ≥100.4° F (38° C) and ≥1 of:
•Symptom onset within 30 days of vaccination Chikungunya- like adverse reactions (1)
- Arthralgia or arthritis
- Myalgia
- Headache
- Back pain
- Rash
- Lymphadenopathy
- Certain neurologic, cardiac, or ocular symptoms
Package insert – IXCHIQ (https://www.fda.gov/vaccines -blood -biologics/ixchiq)
•Chikungunya -like adverse reactions
-11.7%  of vaccine recipients and 0.6% of placebo recipients
•Severe reactions  preventing daily activity or requiring medical
intervention
-1.6%  vaccine recipients vs 0% of placebo recipients
•Prolonged reactions  with  duration ≥30 days
-0.5%  vaccine recipients vs 0% of placebo recipients
Chikungunya- like adverse reactions (2)
Two serious adverse events considered related to vaccination
•58-year -old female, history of
fibromyalgia and hypertension
•Severe myalgia
•Hospitalized for 6 days for pain
management and diagnostic procedures•66-year -old male, history of
hypertension
•Myalgia, high fever, atrial fibrillation,
and hypovolemic hyponatremia
•Hospitalized  for 4 days
FDA Clinical Review Memo (https://www.fda.gov/vaccines -blood -biologics/ixchiq)
ACIP Work Group summary of CHIK -LA safety in Evidence
to Recommendations, February 2024
•Reactogenic vaccine but similar adverse event rates to some other
vaccines
•Important to monitor for rare adverse events post- licensure as sample
size of ~3,500 vaccinated subjects too small to detect rare events
Post -marketing studies
•FDA-required post -marketing studies
-Vaccine effectiveness study in persons aged ≥12 years with safety component (Brazil)
-Pragmatic randomized controlled trial in ≥10,000 individuals to assess effectiveness
and safety
Post -marketing studies
•FDA-required post -marketing studies
-Vaccine effectiveness study in persons aged ≥12 years with safety component (Brazil)
-Pragmatic randomized controlled trial in ≥10,000 individuals to assess effectiveness
and safety
•Additional safety data collection
-Valneva conducting safety study of 5,000 U.S. travelers for medically attended
adverse events of special interest
-Observational registry study of pregnant women in Brazil
Post -licensure surveillance for adverse
events following use of CHIK- LA
•National reporting system for adverse events (AE) following vaccination co- managed by CDC
and FDA
•Designed to detect rare or previously unreported AE or changes in reporting patterns that
might signal a potential safety concern that warrants further investigation
•Anyone (e.g., healthcare providers, patients, vaccine manufacturers) can submit reports
•Effective in intended role as early warning system but limitations includeVaccine Adverse Event Reporting System (VAERS)
-Under -and over -reporting, variable report quality and
accuracy, lack of data on vaccine doses administered,
and lack of unvaccinated comparator group
•Generally cannot determine if AEs caused by
vaccine
Timeline
Licensure
November 2023ACIP
recommendations
February 2024Exact timing of
distribution
unknown*
*First report (non -serious event ) to VAERS received May 6, 2024
28 AEs reported to VAERS after CHIK -LA vaccine
administered in May -Dec 2024*
*Excludes 1 foreign report (non- serious)28 AEs reported
22 non- serious 6 serious
22 n on-serious AEs
22 non- serious AE
10 chikungunya -like
adverse reactions4 arthralgia or
arthritis without
fever8 other*
*Syncope (n=1), flushing (n=1), rash/headache (n=1), musculoskeletal pain (n=1), low grade
fever/headache (n=2), respiratory tract symptoms (n=2)
Serious adverse events (SAEs)
Any adverse event associated with use of biological
product, whether or not considered product -related,
that results in:
•Death
•Life-threatening adverse experience
•Inpatient hospitalization  or prolongation of existing
hospitalization
•Persistent or significant disability/incapacity
•Congenital anomaly/birth defect
•Other medically important event  that may jeopardize
patient and may require intervention to prevent one of the
outcomes listedFDA definition of SAE per federal law
Code of Federal Regulations Title 21 (https://www.ecfr.gov/current/title -21/chapter -I/subchapter -F/part -600/subpart -D/section -600.80)6 SAEs
5 hospitalizations1 other medically
important event
Any adverse event associated with use of biological
product, whether or not considered product -related,
that results in:
•Death
•Life-threatening adverse experience
•Inpatient hospitalization  or prolongation of existing
hospitalization
•Persistent or significant disability/incapacity
•Congenital anomaly/birth defect
•Other medically important event  that may jeopardize
patient and may require intervention to prevent one of the
outcomes listedFDA definition of SAE per federal law
Code of Federal Regulations Title 21 (https://www.ecfr.gov/current/title -21/chapter -I/subchapter -F/part -600/subpart -D/section -600.80)6 SAEs
5 hospitalizations1 other medically
important event
When SAEs reported to VAERS,
attempts made to collect additional
information (e.g., medical records)
Case 1: 83 -year -old male
Case 1: 83 -year -old male
Coronary artery disease Hypertension
Hyperlipidemia
Chronic
thrombocytopeniaChronic heart failure
Chronic kidney disease
Multiple medications to treat comorbidities
Active at baseline
•Received CHIK -LA vaccine
for travel to South America
and AfricaCase 1: 83 -year -old male
Coronary artery disease Hypertension
Hyperlipidemia
Chronic
thrombocytopeniaChronic heart failure
Chronic kidney disease
Multiple medications to treat comorbidities
Active at baseline
Case  1. 83 -year -old male
Day 0:
Received
CHIK -LA
 (only)

Case  1. 83 -year -old male
Day 0:
Received
CHIK -LA
 (only)Day 3:
Initial
symptoms

Case  1. 83 -year -old male
Day 0:
Received
CHIK -LA
 (only)Day 3:
Initial
symptoms
Myalgia, arthralgia,
mild fever, chills, headache, generalized weakness, brain fog,
anorexia, severe
fatigue, unsteady gait
Case  1. 83 -year -old male
Day 0:
Received
CHIK -LA
 (only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weakness

Case  1. 83 -year -old male
Day 0:
Received
CHIK -LA
 (only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weakness
Determined to have
acute kidney injury likely from dehydration; brain MRI and head CT - no acute changes;
discharged home
Case  1. 83 -year -old male
Day 0:
Received
CHIK -LA
 (only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weaknessDay 11: Returned to
hospital with persistent
weakness; admitted
Left lower extremity (hip flexor) weakness, myalgia,
fatigue

Case  1. 83 -year -old male
Day 0:
Received
CHIK -LA
 (only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weaknessDay 11: Returned to
hospital with persistent
weakness; admitted
Left lower extremity (hip flexor) weakness, myalgia,
fatigue
Leukopenia, acute on chronic thrombocytopenia,
elevated liver function tests; declined lumbar puncture

Case  1. 83 -year -old male
Day 0:
Received
CHIK -LA
 (only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weaknessDay 11: Returned to
hospital with persistent
weakness; admitted
Left lower extremity (hip flexor) weakness, myalgia,
fatigue
Leukopenia, acute on chronic thrombocytopenia,
elevated liver function tests; declined lumbar puncture
COVID, influenza A/B, RSV PCR: negative
Blood cultures: no growth

Case  1. 83 -year -old male
Day 0:
Received
CHIK -LA
 (only)Day 3:
Initial
symptomsDay 7: Presents to ED
with ongoing
generalized weaknessDay 11: Returned to
hospital with persistent
weakness; admitted

Case  1. Encephalopathy in 83-year -old male
•Discharge diagnosis: Encephalopathy and generalized weakness -
suspected association with chikungunya vaccination
•Completely resolved after 3.5 weeks
Case  1. Encephalopathy in 83 -year -old male
Day 0:
Received
CHIK -LA
 (only)Day 3:
Initial
symptoms
Myalgia, arthralgia,
mild fever, chills, headache, generalized weakness, brain fog,
anorexia, severe
fatigue, unsteady gaitDay 7: Presents to ED
with ongoing
generalized weakness
Determined to have acute kidney injury likely from dehydration
Brain MRI and head CT
- no acute changes
Discharged homeDay 11: Returned to
hospital with persistent
weakness; admitted
Left lower extremity (hip flexor) weakness, myalgia, fatigue
Leukopenia, acute on chronic thrombocytopenia,
elevated liver function tests; declined lumbar puncture
COVID –19, influenza A/B, RSV PCR: negative
Blood cultures: no growth

Case  2. 77 -year -old male
Coronary artery disease
Hypothyroidism
Selective IgA deficiencyHypertension
Benign prostatic
hyperplasia
Several medications to treat comorbidities
Active at baselineHyperlipidemia
Case  2. 77 -year -old male
Coronary artery disease
Hypothyroidism
Selective IgA deficiencyHypertension
Benign prostatic
hyperplasia
Several medications to treat comorbidities
Active at baseline•Received CHIK -LA vaccine
for travel to Southeast AsiaHyperlipidemia
Case  2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VC*
*JE-VC: Inactivated Vero cell culture -derived JE vaccine
Case  2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptoms

Case  2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptoms
Severe fatigue,
fever, diarrhea, myalgia, urinary urgency

Case  2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent Care
Diagnosed
with viral illness

Case  2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Profound weakness with inability
to stand and intermittent confusion; no dysuria or macroscopic hematuria
Admission diagnosis of fever of
unknown origin, diarrhea, dehydration, hyponatremia,
hypochloremia, and suspected
urinary tract infection

Case  2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Urinalysis: Negative
Case  2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Urinalysis: Negative
COVID PCR, influenza A/B
antigen: negative
Blood cultures: no growth
Case  2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Urinalysis: Negative
COVID PCR, influenza A/B
antigen: negative
Blood cultures: no growth
Brain MRI: no acute intracranial
abnormalities
Case  2. 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VC*Day 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Urinalysis: Negative
COVID PCR, influenza A/B
antigen: negative
Blood cultures: no growth
Brain MRI: no acute intracranial
abnormalities
•Discharge diagnosis: Acute metabolic encephalopathy – possible
association with vaccination –  and fever of unknown origin (resolved)Case  2. Encephalopathy in 77 -year -old male
Case  2. Encephalopathy in 77 -year -old male
Day 0:
Received
CHIK -LA &
JE-VCDay 4:
Initial
symptomsDay 6:
Presented to
Urgent CareDay 8: Presented to
hospital with
worsening
symptoms; admitted
Day 19:
Readmitted with
urinary retention
for ~24 hours
•At ~4 months after onset: Still recovering with ongoing weaknessCase  2. Encephalopathy in 77 -year -old male: outcome
Day 0:
Received
CHIK -LA &
JE-VC*Day 4:
Initial
symptoms
Severe fatigue,
fever, diarrhea, myalgia, urinary urgencyDay 6:
Presented to
Urgent Care
Diagnosed with viral illnessDay 8: Presented to
hospital with
worsening
symptoms; admitted
Profound weakness with inability to stand and intermittent confusion; no dysuria or macroscopic hematuria
Admission diagnosis of fever of
unknown origin, diarrhea, dehydration, hyponatremia,
hypochloremia, and suspected
urinary tract infection
*JE-VC: Inactivated Vero cell culture -derived JE vaccine
Urinalysis: Negative
COVID PCR, influenza A/B
antigen: negative
Blood cultures: no growth
Brain MRI: no acute intracranial
abnormalitiesDay 19:
Readmitted for
~24 hours with
urinary retentionCase  2. Encephalopathy in 77 -year -old male
Case  3. 86-year -old male
Diabetes mellitus
Medications to manage comorbiditiesHypertension
Heart failure
Hyperlipidemia AnemiaHypothyroidism
Case  3. 86-year -old male
Diabetes mellitus
Medications to manage comorbiditiesHypertension
Heart failure
Hyperlipidemia AnemiaHypothyroidism•Received CHIK -LA vaccine
for travel to South Asia
Case  3. 86 -year -old male
Day 0:
Received
CHIK -LA

Case  3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptoms
Lethargy,
drowsiness,
fever
Case  3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptoms
Lethargy,
drowsiness,
feverDeterioration
in mental
status,
shortness of
breath
Case  3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptomsDay 8:
Hospitalized,
admitted to ICU
Altered mental
status, acute
encephalopathy
secondary to
hyponatremia
(118 mmol/L),
shortness of
breath
Case  3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptomsDay 8:
Hospitalized,
admitted to ICU
Hypokalemia, hypochloremia,
hypocalcemia, hypomagnesemiaElevated liver function tests
Case  3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptomsDay 8:
Hospitalized,
admitted to ICU
Hypokalemia, hypochloremia,
hypocalcemia, hypomagnesemiaElevated liver function tests
CT head: No acute abnormalities
Chest X -ray: bilateral infiltrates
Echocardiogram: Small pericardial effusion
Case  3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptomsDay 8:
Hospitalized,
admitted to ICU
Hypokalemia, hypochloremia,
hypocalcemia, hypomagnesemiaElevated liver function tests
CT head: No acute abnormalities
Chest X -ray: bilateral infiltrates
Echocardiogram: Small pericardial effusion
Day 13 post -vaccination serum
sample: chikungunya virus RNA
Case  3. 86 -year -old male
Day 0:
Received
CHIK -LADay 3:
Initial
symptomsDay 8:
Hospitalized,
admitted to ICU
Day 31:
Discharged
after 23 -day
hospitalization
Case  3. Metabolic encephalopathy  in 83-year -old male
•Discharge diagnosis:
-Toxic metabolic encephalopathy
-Fever possibly related to a post- vaccination inflammatory response
with possible superadded bacterial pneumonia
•Mostly recovered at 1 month after discharge from hospital
Case  4. 68-year -old male
Prostate cancer*
Medications to manage comorbiditiesHypertension
Hypothyroidism Dyslipidemia
*Radiation therapy pending
Case  4. 68-year -old male
Prostate cancer*
Medications to manage comorbiditiesHypertension
Hypothyroidism Dyslipidemia
*Radiation therapy pending•Received CHIK -LA vaccine
for trip to Southeast Asia
Case  4. 68 -year -old male
Day 0:
Received
CHIK -LA*
*At intervals 8– 15 days earlier, received six inactivated vaccines: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A
Case  4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptoms
Fever,
headache,
fatigue, body
achesPhotophobia and neck
stiffness
Case  4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
Case  4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
CSF pleocytosis (109 WBC/µL with
mononuclear predominance; 157 RBC/µL)
Case  4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
CSF pleocytosis (109 WBC/µL with
mononuclear predominance; 157 RBC/µL)
Meningoencephalitis and respiratory PCR
panels negative, CSF culture no growth
Case  4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
CSF pleocytosis (109 WBC/µL with
mononuclear predominance; 157 RBC/µL)
Meningoencephalitis and respiratory PCR
panels negative, CSF culture no growth
Brain MRI, CT: no acute abnormalities
Case  4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
CSF pleocytosis (109 WBC/µL with
mononuclear predominance; 157 RBC/µL)
Meningoencephalitis and respiratory PCR
panels negative, CSF culture no growth
Brain MRI, CT: no acute abnormalities
CSF chikungunya testing: IgM and
neutralizing antibodies detected
Case  4. 68 -year -old male
Day 0:
Received
CHIK -LA
Day 5:
Initial symptomsDay 12: Hospitalized
with meningitis
•Discharge diagnoses: Meningismus /aseptic meningitis likely
secondary to recent vaccination
•Status : Headache and fatigue initially persisted but fully recovered by
~1 monthCase  4. Meningitis in 68- year -old male
Case  4. Meningitis in 68- year -old male
Day 0:
Received
CHIK -LA*
*At intervals 8– 15 days earlier, received six inactivated vaccines: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis ADay 5:
Initial symptoms
Fever,
headache,
fatigue, body
achesPhotophobia and neck
stiffnessDay 12: Hospitalized
with meningitis
CSF pleocytosis (109 WBC/µL with
mononuclear predominance; 157 RBC/µL)
Meningoencephalitis and respiratory PCR
panels negative, CSF culture no growth
Brain MRI, CT: no acute abnormalities
CSF chikungunya testing: IgM and
neutralizing antibodies detected
Case  5. 67-year -old male
Hyperlipidemia
Medication to manage condition
Case  5. 67-year -old male
Hyperlipidemia
Medication to manage condition•Received CHIK -LA vaccine
for trip to central America
Case  5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccine*
*19 days prior: COVID -19 and inactivated influenza vaccines
Case  5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptoms
Myalgia, fever
Case  5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 6:
Palpitations
Case  5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular responseDay 6:
Palpitations
Case  5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular responseDay 6:
Palpitations
Elevated troponin, proBNP
Nuclear stress test: suspicious for small infarct
Case  5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular responseDay 6:
Palpitations
Elevated troponin, proBNP
Nuclear stress test: suspicious for small infarct
No evidence of pulmonary embolism, normal
thyroid -stimulating hormone
Case  5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular responseDay 6:
Palpitations
Elevated troponin, proBNP
Nuclear stress test: suspicious for small infarct
No evidence of pulmonary embolism, normal
thyroid -stimulating hormone
COVID, influenza, RSV PCR: negative
Case  5. 67 -year -old male
Day 0:
Received
CHIK -LA & oral
typhoid vaccineDay 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular responseDay 6:
Palpitations
•Discharge diagnoses: atrial flutter with rapid ventricular response,
suspected small non- ST segment elevation myocardial infarction
•Status : Fully recovered on discharge, medication ongoing 3 months laterCase  5. Atrial flutter and non -ST segment elevation
myocardial infarction in 67- year -old male
Case  5. Atrial flutter and non -ST segment elevation
myocardial infarction in 67- year -old male with
Day 0:
Received
CHIK -LA & oral
typhoid vaccine*Day 4:
Initial
symptomsDay 8: Presented to
hospital with atrial
flutter with rapid
ventricular response
*19 days prior: COVID -19 and inactivated influenza vaccinesMyalgia, fever
1 day laterDay 6:
Palpitations
Elevated troponin, proBNP
Nuclear stress test: suspicious for small infarct
No evidence of pulmonary embolism, normal
thyroid -stimulating hormone
COVID, influenza, RSV PCR: negative
Case  6. 74 -year -old male
Ischemic
cardiomyopathy
Medications to manage comorbiditiesCoronary artery diseaseHypotensionChronic leukopenia
Chronic thrombocytopenia
Case  6. 74 -year -old male
Ischemic
cardiomyopathy
Medications to manage comorbiditiesCoronary artery diseaseHypotensionChronic leukopenia•Received CHIK -LA vaccine
for planned travel to
Southeast Asia
Chronic
thrombocytopenia
Case  6. 74 -year -old male
Day 0:
Received
CHIK -LA
&  JE -VC*
*JE-VC: Inactivated Vero cell culture -derived JE vaccine
Case  6. 74 -year -old male
Day 3:
Initial
symptomsDay 0:
Received
CHIK -LA
&  JE -VC
Fatigue, weakness,
lightheadedness,
mild shortness of
breath, noted
hypotension
Case  6. 74 -year -old male
Day 3:
Initial
symptomsDay 8:
Presented
to internistDay 0:
Received
CHIK -LA
&  JE -VC
Severe
hypotension
No evidence
of heart
failure
Case  6. 74 -year -old male
Day 3:
Initial
symptomsDay 8:
Presented
to internistDay 0:
Received
CHIK -LA
&  JE -VCDay 10:
Blood
collection
Leukopenia,
thrombocytopenia
Case  6. 74 -year -old male
Day 3:
Initial
symptomsDay 8:
Presented
to internistDay 0:
Received
CHIK -LA
&  JE -VCDay 15:
Follow -up visit
to internist
Some
improvement in
blood pressureDay 10:
Blood
collection
Case  6. 74 -year -old male#
Day 3:
Initial
symptomsDay 8:
Presented
to internistDay 0:
Received
CHIK -LA
&  JE -VCDay 15:
Follow -up visit
to internist
#SAE as “Other medically important event”Day 10:
Blood
collection
Case  6. Worsened and prolonged hypotension in 74 -
year -old male
•Final diagnosis: Episode of worsened and prolonged hypotension on the
background of pre -existing cardiomyopathy and hypotension - likely
related to CHIK -LA vaccination
•Resolved within ~2 weeks
Case  6. 74 -year -old male#
Day 3:
Initial
symptomsDay 8:
Presented
to internistDay 0:
Received
CHIK -LA
&  JE -VC*
*JE-VC: Inactivated Vero cell culture -derived JE vaccineFatigue, weakness,
lightheadedness,
mild shortness of
breath, noted
hypotension Day 15:
Follow -up visit
to internist
Severe
hypotension
No evidence
of heart
failure Some
improvement in
blood pressure
#SAE as “Other medically important event”Day 10:
Blood
collection
Leukopenia,
thrombocytopenia
Summary of case characteristics (N=6)
Age
(yrs) Sex Key comorbiditiesCo-administered
vaccinesSymptom
onset (days) Discharge diagnosis(es) Chikungunya testing
83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3
Encephalopathy
Generalized weaknessN/A
77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia,
hyperlipidemia, hypertension, IgA
deficiencyJapanese encephalitis (inactivated)4
Acute metabolic encephalopathy
Fever of unknown originN/A
86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy
Fever possibly related to post -
vaccination inflammatory responseRT-PCR on serum on
day 13: positive
68 MaleProstate cancer, hypothyroidism,
hypertension, dyslipidemia_†
5 Aseptic meningitisIgM & neutralizing
antibodies in CSF
67 Male HyperlipidemiaTyphoid
(oral, live)*4Atrial flutter
Non -ST segment elevation myocardial
infarction (NSTEMI)N/A
74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese
encephalitis
(inactivated)3
Worsened and prolonged hypotension
on background of pre -existing
cardiomyopathy and hypotensionN/A
*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not available
Age
(yrs) Sex Key comorbiditiesCo-administered
vaccinesSymptom
onset (days) Discharge diagnosis(es) Chikungunya testing
83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3
Encephalopathy
Generalized weaknessN/A
77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia,
hyperlipidemia, hypertension, IgA
deficiencyJapanese encephalitis (inactivated)4
Acute metabolic encephalopathy
Fever of unknown originN/A
86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy
Fever possibly related to post -
vaccination inflammatory responseRT-PCR on serum on
day 13: positive
68 MaleProstate cancer, hypothyroidism,
hypertension, dyslipidemia_†
5 Aseptic meningitisIgM & neutralizing
antibodies in CSF
67 Male HyperlipidemiaTyphoid
(oral, live)*4Atrial flutter
Non -ST segment elevation myocardial
infarction (NSTEMI)N/A
74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese
encephalitis
(inactivated)3
Worsened and prolonged hypotension
on background of pre -existing
cardiomyopathy and hypotensionN/A
*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not availableSummary of case characteristics (N=6)
Age
(yrs) Sex Key comorbiditiesCo-administered
vaccinesSymptom
onset (days) Discharge diagnosis(es) Chikungunya testing
83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3
Encephalopathy
Generalized weaknessN/A
77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia,
hyperlipidemia, hypertension, IgA
deficiencyJapanese encephalitis (inactivated)4
Acute metabolic encephalopathy
Fever of unknown originN/A
86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy
Fever possibly related to post -
vaccination inflammatory responseRT-PCR on serum on
day 13: positive
68 MaleProstate cancer, hypothyroidism,
hypertension, dyslipidemia_†
5 Aseptic meningitisIgM & neutralizing
antibodies in CSF
67 Male HyperlipidemiaTyphoid
(oral, live)*4Atrial flutter
Non -ST segment elevation myocardial
infarction (NSTEMI)N/A
74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese encephalitis (inactivated)3
Worsened and prolonged hypotension
on background of pre -existing
cardiomyopathy and hypotensionN/A
*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not availableSummary of case characteristics (N=6)
Age
(yrs) Sex Key comorbiditiesCo-administered
vaccinesSymptom
onset (days) Discharge diagnosis(es) Chikungunya testing
83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3
Encephalopathy
Generalized weaknessN/A
77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia,
hyperlipidemia, hypertension, IgA
deficiencyJapanese encephalitis (inactivated)4
Acute metabolic encephalopathy
Fever of unknown originN/A
86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy
Fever possibly related to post -
vaccination inflammatory responseRT-PCR on serum on
day 13: positive
68 MaleProstate cancer, hypothyroidism,
hypertension, dyslipidemia_†
5 Aseptic meningitisIgM & neutralizing
antibodies in CSF
67 Male HyperlipidemiaTyphoid
(oral, live)*4Atrial flutter
Non -ST segment elevation myocardial
infarction (NSTEMI)N/A
74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese
encephalitis
(inactivated)3
Worsened and prolonged hypotension
on background of pre -existing
cardiomyopathy and hypotensionN/A
*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not availableSummary of case characteristics (N=6)
clinical consult services†
support enhanced surveillance
clinical research
†More information about clinical consults available at :
https://www.cdc.gov/vaccine -safety -systems/hcp/cisa/index.html8 participating medical
research centers with
vaccine safety expertsClinical
Immunization
Safety
Assessment
(CISA) Project C IS A

•Available medical records for each of neurologic (n=4) and cardiac (n=2)
reports reviewed with experts in vaccine safety, infectious diseases, cardiology and neurology
•For each report, at least one CISA expert considered association of CHIK -LA
with SAE plausible
•However, experts noted difficulty differentiating between general reactogenicity in older patients with comorbidities leading to SAE versus chikungunya vaccine causing SAESummary of CISA review of SAEs following CHIK -LA
reported to VAERS
•Temporal association ≠ causal association
•Sometimes concomitant or recent administration of other vaccines
•Comprehensive investigations of possible etiologies not always
conducted or available
•Unlike in controlled clinical trials, no unvaccinated comparator groupGenerally cannot determine causality from VAERS data
Shimabukuro TT, et al. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS). Vaccine 2015;33:4398 -4405.
All events began within 3 –5 days of vaccination
For 3 patients with co -administration of other vaccines (i.e., JE,
typhoid), association with other vaccines less likely1-3
Investigations did not indicate clear alternate etiologies for any
patient and most (n=5) discharge summaries noted potential
association with vaccination
For 2 cases with chikungunya laboratory testing, results
suggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs
1. Rabe IB et al, Vaccine 2015;   2. Walker WL et al, Vaccine 2018;   3. Begier  EM et al. Clin Infect Dis 2004.
All events began within 3 –5 days of vaccination
For 3 patients with co -administration of other vaccines (i.e., JE,
typhoid), association with other vaccines less likely1-3
Investigations did not indicate clear alternate etiologies for any
patient and most (n=5) discharge summaries noted potential
association with vaccination
For 2 cases with chikungunya laboratory testing, results
suggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs
1. Rabe IB et al, Vaccine 2015;   2. Walker WL et al, Vaccine 2018;   3. Begier  EM et al. Clin Infect Dis 2004.
All events began within 3 –5 days of vaccination
For 3 patients with co -administration of other vaccines (i.e., JE,
typhoid), association with other vaccines less likely1-3
Investigations did not indicate clear alternate etiologies for any
patient and most (n=5) discharge summaries noted potential
association with vaccination
For 2 cases with chikungunya laboratory testing, results
suggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs
1. Rabe IB et al, Vaccine 2015;   2. Walker WL et al, Vaccine 2018;   3. Begier  EM et al. Clin Infect Dis 2004.
All events began within 3 –5 days of vaccination
For 3 patients with co -administration of other vaccines (i.e., JE,
typhoid), association with other vaccines less likely1-3
Investigations did not indicate clear alternate etiologies for any
patient and most (n=5) discharge summaries noted potential
association with vaccination
For 2 cases with chikungunya laboratory testing, results
suggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs
1. Rabe IB et al, Vaccine 2015;   2. Walker WL et al, Vaccine 2018;   3. Begier  EM et al. Clin Infect Dis 2004.
CHIK -LA and SAEs in persons ≥65 years
•Immunosenescence  affects older person’s ability to adequately control
replication of live attenuated vaccine virus
-Example: With live attenuated yellow fever vaccine, SAEs more frequent in older
persons, and age ≥ 60 years is precaution for use
•Wild -type chikungunya virus infections more likely to result in severe
disease in older adults
Estimating incidence of SAEs after CHIK -LA
•Difficult as limited  data on vaccine doses distributed  and very limited  data
on doses administered
•Obtained data from commercial source (IQVIA; private -sector company that
provides healthcare data)
-Sales data : Weekly Sales Perspectives (WSP) data are unprojected (i.e., actual)
sales for prescription products (vaccinations) sold to retail, non -retail, and mail
channels and capture about ~90% of total sales*
-Administration data : National Prescription Audit (NPA) data represent projected
estimates  of vaccinations administered in retail and long -term care pharmacies
*Information from IQVIA
Confidential and pre -decisional – for official use onlyCHIK -LA (IXCHIQ) weekly and cumulative sales  as of week ending December 27, 2024
IQVIA SMART Weekly Sales Perspective (WSP)
13,891 total
doses
distributed
Pharmacy total = 1,275 (9%) Medical office total = 12,616 (91%)
Confidential and pre -decisional – for official use onlyCHIK -LA (IXCHIQ) weekly and cumulative vaccinations administered in pharmacies ,
as of week ending December 27, 2024. IQVIA SMART NPA Weekly Extended Insights
Estimated
928 doses
administered
in pharmacies
Confidential and pre -decisional – for official use onlyCHIK -LA (IXCHIQ) pharmacy administrations by age, March 3– December 27, 2024
IQVIA SMART NPA Weekly Extended Insights
53% doses
administered
to individuals
aged ≥65 years
N=928
No.
eventsEstimated rate of events
per 100,000 doses administered
(95% CI)Estimated rate of doses administered
resulting in 1 event
(95% CI)
SAEs 682 per 100,000
(30–180) 1 SAE per 1,220 doses
(1 per 3,333 doses to 1 per 556 doses)
*Based on VAERS reports, IQVIA data on doses distributed (N=13,891 doses), and IQVIA data that 52.7% (n=7,320) administered to p ersons aged ≥65 yrsRisk estimates for SAEs and hospitalizations among persons aged
≥65 years*
No.
eventsEstimated rate of events
per 100,000 doses administered
(95% CI)Estimated rate of doses administered
resulting in 1 event
(95% CI)
SAEs 682 per 100,000
(30–180) 1 SAE per 1,220 doses
(1 per 3,333 doses to 1 per 556 doses)
Hospitalizations 568 per 100,000
(20–160) 1 hospitalization per 1,471 doses
(1 per 5,000 doses to 1 per 625 doses)
*Based on VAERS reports, IQVIA data on doses distributed (N=13,891 doses), and IQVIA data that 52.7% (n=7,320) administered to p ersons aged ≥65 yrsRisk estimates for SAEs and hospitalizations among persons aged
≥65 years*
Limitations of risk estimates
•Calculations limited by potential imprecision in numerator and
denominator data
-Unknown completeness of reporting of events to VAERS
-Potential inaccuracies in vaccine administration data overall and by age group
•All VAERS SAE reports included in calculations but cannot confirm causal link between vaccination and all reported events
•Overall low certainty in estimates
•Updated data as of March 21, 2025
-0 SAEs  and 9 non- serious AEs reported to VAERS in United States*
-Additional ~4,250 CHIK -LA doses sold#
•Risk estimates not updated for this presentation
-Delays in CHIK -LA reports to VAERS (median 13 days)
-~2,375 doses sold in last ~2 weeks of 2024 and likely not
administered in 2024
-Unknown impact of CDC alert in February 2025 about
hospitalizations after CHIK -LA in ages ≥65 years
-With updated data, risk estimates lower but within 95% confidence limits of previous estimates
 Update: 2025  VAERS data
*Excludes 6 (non -serious) reports from other countries; #IQVIA data
https://www.cdc.gov/chikungunya/prevention/chikungunya -vaccine.html
Work Group considerations regarding SAEs
following CHIK -LA
All SAEs in persons aged ≥65 years
Findings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to
~7,700 persons aged ≥65 years
VAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65
years, but further investigation warranted to better define true risk
For individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of
vaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known
risks for severe disease and hospitalization in this age groupFactors considered by Work Group
All SAEs in persons aged ≥65 years
Association of CHIK -LA with SAEs is plausible, but causal association for each event not determined
Findings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to
~7,700 persons aged ≥65 years
VAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65
years, but further investigation warranted to better define true risk
For individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of
vaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known
risks for severe disease and hospitalization in this age groupFactors considered by Work Group
All SAEs in persons aged ≥65 years
Association of CHIK -LA with SAEs is plausible, but causal association for each event not determined
Findings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to
~7,700 persons aged ≥65 years
VAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65
years, but further investigation warranted to better define true risk
For individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of
vaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known
risks for severe disease and hospitalization in this age groupFactors considered by Work Group
All SAEs in persons aged ≥65 years
Association of CHIK -LA with SAEs is plausible, but causal association for each event not determined
Findings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to
~7,700 persons aged ≥65 years
VAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65
years, but further investigation warranted to better define true risk
For individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of
vaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known
risks for severe disease and hospitalization in this age groupFactors considered by Work Group
All SAEs in persons aged ≥65 years
Association of CHIK -LA with SAEs is plausible, but causal association for each event not determined
Findings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to
~7,700 persons aged ≥65 years
VAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65
years, but further investigation warranted to better define true risk
For individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of
vaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known
risks for severe disease and hospitalization in this age groupFactors considered by Work Group
Age ≥65 years should be a precaution * for use of CHIK -LA
•In general, vaccination should be deferred
•Vaccination might be indicated if benefit from protection from vaccination
outweighs risk for adverse reaction
*https://www.cdc.gov/vaccines/hcp/imz -best -practices/contraindications -precautions.html
Work Group proposes revising recommendations for
use of CHIK -LA among travelers
•In accordance with updated Evidence to Recommendations for travelers
presented in earlier presentation for CHIK -VLP
•In consideration of safety signal following use of vaccine in persons aged ≥65 years
Existing CHIK -LA recommendations for travelers*
Chikungunya vaccine is recommended  for persons aged ≥18 years traveling
to a country or territory where there is a chikungunya outbreak.
In addition, chikungunya vaccine may be considered for the following
persons traveling to a country or territory without an outbreak but with
evidence of chikungunya virus transmission among humans within the last 5 years
-Persons aged >65 years, particularly those with underlying medical conditions,
who are likely to have at least moderate exposure to mosquitoes, OR
-Persons staying for a cumulative period of 6 months or more
*Approved in February 2024
Existing CHIK -LA recommendations for travelers*
Chikungunya vaccine is recommended  for persons aged ≥18 years traveling
to a country or territory where there is a chikungunya outbreak.
In addition, chikungunya vaccine may be considered for the following
persons traveling to a country or territory without an outbreak but with
evidence of chikungunya virus transmission among humans within the last 5 years
-Persons aged >65 years, particularly those with underlying medical conditions,
who are likely to have at least moderate exposure to mosquitoes, OR
-Persons staying for a cumulative period of 6 months or more
*Approved in February 2024
ACIP recommends live attenuated chikungunya vaccine or persons aged ≥18
years traveling to a country or territory where there is a chikungunya
outbreak.
In addition, live attenuated chikungunya vaccine may be considered  for
persons aged ≥18 years# traveling or taking up residence in a country or
territory without an outbreak but with elevated risk for US travelers if
planning travel for an extended period of time e.g., 6 months or more.Revised draft recommendations for CHIK -LA among
travelers#
#Age ≥65 years is a precaution for use of CHIK -LA
Arboviral Diseases Branch, CDC
•Rebekah Sutter
•Erin Staples
Immunization Safety Office, CDC
•Sarah Meyer
•Michael McNeil
•Elaine MillerAcknowledgements
Immunization Services Division, CDC
•Seth Meador
•Suchita Patel
Clinical Immunization Safety
Assessment (CISA) vaccine safety
experts
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: Surveillance for adverse events following use of  live attenuated chikungunya vaccine and its use  among travelersNational Center for Emerging and Zoonotic Infectious Diseases Dr. Susan Hills CDC Lead, Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado Advisory Committee on Immunization Practices meeting April 16 , 2025 Background on live attenuated  chikungunya vaccine Live attenuated chikungunya vaccine (CHIK -LA) …


05 Hills chikungunya 508

Clinical guidance for use of virus -like particle
chikungunya vaccine in pregnant and breastfeeding
womenNational Center for Emerging and Zoonotic Infectious Diseases
Susan Hills MBBS MTH
CDC Lead, Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Division of Vector- Borne Diseases
Fort Collins, ColoradoDana Meaney- Delman, MD MPH FACOG
Principal Deputy Director and Chief Medical Officer
National Center on Birth Defects and Developmental
Disabilities
Chamblee, Georgia
Advisory Committee on Immunization Practices meeting
April 16 , 2025
Clinical guidance for use of virus -like
particle chikungunya vaccine (CHIK- VLP) in
pregnant women
•Clinical disease similar to non -pregnant individualsPresentation of chikungunya among pregnant women
•Adverse outcomes such as fetal loss, stillbirth, or preterm birth
documented but rare
-Mouse studies and examination of placentas from infected women suggest
placenta is refractory to chikungunya virus infection1,2
•Infection commonly  results in adverse neonatal outcomes if pregnant
woman infected around time of delivery
-Intrapartum transmission occurs in ~30% –50% cases3–6
-Mechanism hypothesized to be maternal blood entering fetal circulation by placental barrier breaches from uterine contractions during labor Outcomes of chikungunya virus infection during
pregnancy
1. Fritel   X et al, Emerg  Infect Dis 2010; 2. Couderc T et al, PLoS Pathog 2008; 3. Gerardin P et al, PLoS Medicine 2008; 4. Ramful D et al, Ped Infect Dis J 2007; 5.
Torres JR et al, Int J Infect Dis 2016; 6. Senanayake MP et al, Ceylon Med J 2009.
•Severe and sometime fatal illness
-In one prospective study 53% (10 of 19 neonates) had severe disease1
•Presentations include encephalopathy, sepsis -like illness, cardiac,
dermatologic, and hemorrhagic manifestations
•Neurocognitive outcomes often poor, particularly if initial clinical
presentation with encephalopathyDisease in neonates infected via intrapartum transmission
Bin S et al, Clin Case Rep 2023
 Jebain  J et al, ID Cases 2020
 Villamil -Gomez W et al, J Trop Ped 2015
1. Gerardin  P et al, PLoS  Medicine 2008
•Young infants infected via
mosquito -borne transmission also
at risk for severe disease, particularly during first few months of life
•Clinical presentations similar to infected neonates Chikungunya and young infants
Valamparampil  JJ et al, Ind J Ped 2009
Gupta D et al, Ind J Ped 2015
•No data available on immunologic response to CHIK -VLP administered
to pregnant women
•General principles of maternal vaccination and experience with other
vaccines
-Transplacental transfer of antibodies confers protection with most vaccines
-Examples of benefits: Decreased hospitalization rates in infants (e.g.,
influenza, COVID -19, RSV vaccines) and decreased preterm birth risk (e.g.,
COVID -19 vaccine)CHIK -VLP vaccination during pregnancy: Immunogenicity
•Data insufficient to determine whether any safety risks from vaccination
during pregnancy as pregnancy an exclusion criteria in clinical trials
•Only one pregnant woman inadvertently vaccinated, was in 1st trimester
-Phase ll study with formulation of vaccine* different to licensed product
-History of 2 ectopic pregnancies
-Last menstrual period 11 days prior to vaccination
-Ectopic pregnancy detected 24 days after vaccination and assessed as
unrelated to vaccinationCHIK -VLP vaccination during pregnancy: Safety
*20µg dose of unadjuvanted vaccine
•DART study in rabbits
-Administered equivalent of human dose of vaccine on 5 occasions (i.e., twice
prior to mating, twice during gestation, and once during lactation)
-Postnatal survival rate within 28 days was lower for kits born to vaccinated
mothers ( 42% ; 95% CI : 32% –53%) compared with kits in control group ( 69% ;
95% CI 58% –80%)
-No adverse effects on other postnatal development parameters
•DART study in rats
-Reduced pup survival rates not observedVaccination during pregnancy: Developmental and
reproductive toxicology (DART) studies
•Travelers and laboratory workers
•Persons in U.S. territories and states with risk of chikungunya virus
transmissionGroups for whom clinical guidance will be relevant
•Protect pregnant woman from disease
•Avoid maternal infection around time of delivery to prevent
intrapartum virus transmission and severe disease in newborn
•Transplacental transfer of antibodies might also protect young infant from mosquito -borne transmission and severe diseaseObjectives of vaccinating pregnant women against
chikungunya
Pregnant women should avoid the risk for chikungunya virus infection, if
possible (e.g., by avoiding travel to an area with virus transmission particularly during an outbreak). Proposed clinical guidance for use of CHIK -VLP in
pregnant women
Pregnancy is a precaution for vaccination with CHIK -VLP based on the lack of
safety and immunogenicity data in pregnant women and potential safety
concerns from the toxicology study in rabbits.
In general, vaccination should be deferred until after delivery. However, in specific
circumstances it might be warranted. If the risk of infection is high and exposure
cannot be avoided, a health care provider should discuss with a pregnant woman
the potential risks of chikungunya virus infection and the potential benefits and
risks of vaccination so that vaccination can be considered.
CHIK -VLP should ideally be administered a minimum of 2 weeks prior to the
expected date of delivery, and preferably earlier, to allow protection around the
time of delivery. Proposed clinical guidance for use of CHIK -VLP in
pregnant women (2)
If pregnant women choose to be vaccinated, deferring vaccination until
after the 1st trimester (after 14 weeks gestation) might be preferred until
there are further data to clarify any potential concerns from the animal
toxicology data. In addition, it is estimated that 20% –25% of all
pregnancies lead to pregnancy loss, and the highest rates occur in the 1st
trimester, so avoiding vaccination in the 1st trimester would avoid any
association with an unrelated pregnancy loss.Proposed clinical guidance for use of CHIK -VLP in
pregnant women (3)
If both CHIK -VLP and CHIK -LA are available, vaccination with CHIK -VLP
would be preferred . Although there are no data, this is based on general
principles that vaccination with non- live vaccines is preferred over
vaccination with live vaccines for pregnant women. Proposed clinical guidance for use of CHIK -VLP in
pregnant women (4)
Guidance maximizing benefits while minimizing
potential risks of vaccination during pregnancy
1. Avoid risk of chikungunya virus exposure, if possible
2. In general, defer vaccination until after delivery
3. If exposure risk high, consider vaccination given risk for severe adverse
outcomes of infection particularly if intrapartum transmission occurs
4. If consider vaccination, where possible avoid 1st trimester and ideally
administer >2 weeks before delivery
5. If both CHIK -VLP and CHIK -LA available, vaccination with non- live CHIK -
VLP preferred
Clinical guidance for use of CHIK- VLP in
breastfeeding women
•Chikungunya viral ribonucleic acid (RNA) detected in breast milk on
very rare occasions1,2
-No studies have reported detection of replicating virus
•Case report describes mother with chikungunya and chikungunya virus
RNA detected in her breast milk who was breastfeeding her 3- month -
old infant1
-No symptoms or laboratory evidence of infection in infantChikungunya and breastfeeding
1. Campos GS et al, Pediatr  Infect Dis J 2017; 2. De Paula Souza et al, Transl  Res 2023.
•No data on any benefits or risks of breastfeeding after vaccination with
CHIK -VLP , including whether chikungunya antibodies present in breast
milk post -vaccination
•In toxicology studies in rabbits and rats, no impact of vaccination on
lactation was observedCHIK -VLP and breastfeeding
•To protect the woman from chikungunya
•Possible added benefit to reduce risk of infection for young infant by
transfer of protective antibodies through breast milkObjectives of vaccinating breastfeeding women
Breastfeeding women and their infants should avoid the risk for
chikungunya virus infection, if possible (e.g., by avoiding travel to an area
with transmission particularly during an outbreak).
Best practice guidelines1 for immunization note that non -live vaccines
pose no risk for mothers who are breastfeeding or their infants. Proposed clinical guidance for use of CHIK -VLP in
breastfeeding women*
*Breastfeeding not a contraindication or precaution for vaccination with CHIK -VLP
1. https://www.cdc.gov/breastfeeding/breastfeeding -special- circumstances/vaccinations -medications -drugs/vaccinations.html
•Haben Debessai, Division of Birth Defects and Infant Disorders
•Erin Staples, Division of Vector- Borne Diseases
•ACOG and AAP members for their review of draft clinical guidance
•Chikungunya Vaccines Work Group membersAcknowledgements
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: Clinical guidance for use of virus -like particle  chikungunya vaccine in pregnant and breastfeeding  womenNational Center for Emerging and Zoonotic Infectious Diseases Susan Hills MBBS MTH CDC Lead, Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector- Borne Diseases Fort Collins, ColoradoDana Meaney- Delman, MD MPH FACOG Principal Deputy Director and Chief Medical Officer National Center on Birth Defects and Developmental  Disabilities Chamblee, Georgia Advisory…


01 Jones Maternal Peds RSV 508

Maternal/Pediatric Respiratory Syncytial Virus (RSV)
Work Group
Jefferson Jones MD MPH FAAP
Co-Lead, Maternal/Pediatric RSV Work Group
Presenting on behalf of
Helen Chu, MD, MPH
Chair, Maternal/Pediatric RSV Work Group
ACIP Meeting
April 16, 2025
1U.S. Centers for Disease Control and Prevention

CDC and ACIP recommend all infants should be protected against
severe RSV disease with either maternal RSV vaccine or nirsevimab
Maternal vaccine
Abrysvo , Pfizer
*Either  maternal RSV vaccine or nirsevimab is given to protect infants against severe RSV disease – only one
is needed in most instances
Pregnant women 32 through 36
weeks’ gestation
Administer September through
January in most of
thecontinental United States†All infants <8 months*
Second season dose for children
ages 8 –19 months at increased risk
of severe RSV disease
Administer October through March
in most of the continental United
States†(as early as possible¥)
† Timing of administration for RSV immunization may differ in jurisdictions with RSV seasonality that differs from most of th e continental United States; ¥ The optimal timing for nirsevimab administration is
shortly before the RSV season begins (e.g., October –November), or within a baby's first week of life if born October through Mar ch (ideally during the birth hospitalization.)Nirsevimab
Beyfortus , Sanofi & AstraZeneca
Today we will be reviewing data on a second, long -acting monoclonal
antibody for protection of infants from severe RSV disease
Maternal vaccine
Abrysvo , Pfizer
*Either  maternal RSV vaccine or an infant antibody is given to protect infants against severe RSV disease –
only one is needed in most instances
Pregnant women 32
through 36 weeks’
gestation
Administer
September through
January in most of
thecontinental
United States†All infants <8 months*
Second season dose for
children ages 8 –19 months
at increased risk of severe
RSV disease
Administer October through
March in most of the
continental United States †
(as early as possible¥)Nirsevimab
Beyfortus , Sanofi &
AstraZeneca Clesrovimab
Merck
Currently not FDA approved
Target action date: 6/10/25
All infants <8 months*
Administer October
through March in most of
the continental United
States † (as early as
possible¥)
† Timing of administration for RSV immunization may differ in jurisdictions with RSV seasonality that differs from most of th e continental United States; ¥ The optimal timing for nirsevimab administration is
shortly before the RSV season begins (e.g., October –November), or within a baby's first week of life if born October through Mar ch (ideally during the birth hospitalization.)
•September 2024
-Maternal/Pediatric RSV work group reviewed and discussed data from Merck on
safety and efficacy of clesrovimab
•October 2024
-ACIP reviewed and discussed data from Merck on safety and efficacy of
clesrovimab and work group interpretation of these data
•November 2024 – April 2025
-Maternal/Pediatric RSV work group reviewed and discussed
•GRADE (Grading of Recommendations, Assessment, Development, and
Evaluations) for clesrovimab
•Evidence to Recommendations Framework for clesrovimabTimeline of Maternal/Pediatric RSV work group and
ACIP review of clesrovimab
•Evidence to Recommendation Framework: Clesrovimab — Ms. Danielle
Moulia (CDC/NCIRD)
•Clinical Considerations — Dr. Jefferson Jones (CDC/NCIRD)Today’s agenda: April 16, 2025
5
•FDA has set a Prescription Drug User Fee Act (PDUFA) date, or target date for
regulation action, of June 10, 2025 , for clesrovimab .
•June 2025 ACIP meeting
-Presentation of any updates to the Evidence to Recommendation Framework and
Clinical Consideration for clesrovimab
-Vote on recommendation of clesrovimab  (pending FDA regulatory action)Clesrovimab : Looking forward
6Source: Merck Press Release, 12/17/2024: https://www.merck.com/news/merck -announces -fda-acceptance -of-biologics -license -application -for-clesrovimab -an-investigational -
long -acting -monoclonal -antibody -designed -to-protect -infants -from -rsv-disease -during -their -first-rsv/
Work group members (external)
ACIP Members
Helen Chu (chair)
Oliver Brooks
Denise JamiesonConsultants
Cody Meissner (Dartmouth Geisel School of Medicine)
Kevin Ault (Western Michigan University)
Pablo Sanchez (Nationwide Children’s Hospital)
Liaisons
James McAuley (IDSA)
Nicole Chaisson  (AAFP)
Sean O’Leary (AAP)
Jennifer Schuster (PIDS)
Molly Howell (AIM)
Stacy Buchanan (NAPNAP)
Caitlin Newhouse (CSTE)Ex Officio Members
Lucia Lee (FDA -CBER)
Yodit Belew (FDA -CDER)
Prabha Viswanathan (FDA -CDER)
Yugenia Hong -Nguyen (FDA -CDER)
Sonnie Kim (NIH -NIAID)
April Killikelly (Public Health Agency of Canada)
Elissa Abrams  (Public Health Agency of Canada)
Jessica Lee (CMS/CMCS)
Terry Dalle -Tezze (HRSA)
Matthew Clark (IHS)
7
Work group members (CDC)
Amanda Payne
Noelle Molinari
Fiona Havers
Pragna Patel
Ruth Link -Gelles
Monica Godfrey
Heidi Moline
Hannah Rosenblum
Manisha Patel
Heather Scobie
Michele Hlavsa CDC ACIP Staff
Melinda Wharton
Stephanie Thomas
Jessica MacNeilMonica Patton
Jarrett Gartin
Dennis Wang
Jordan Singleton
Fatimah Dawood
Agustin Lopez
Lakshmi Panagiotakopoulos
Suzanne Heitfeld
Molly Gaines -McCollom
Amber Rose Kautz
Allison CieslaCDC
Jefferson Jones (co -lead)
Danielle Moulia (co -lead)
Meredith McMorrow
Mila Prill
Natalie Thornburg
Ismael Ortega -Sanchez
Melissa Coughlin
Jamison Pike
Lauren Roper
Tami Skoff
Angie Campbell
Michael Melgar
Amadea BrittonChristine Olson
Anne Hause
Andrew Leidner
David Shay
Pedro Moro
Tarayn  Fairlie
John Su
Micheal McNeal
Julianne Gee
Naomi Tepper
Ellen Boundy
Alaya Koneru
Melissa Taylor
Ebony Thomas
8
For more information, contact CDC
1-800-CDC-INFO (232 -4636)
TTY:  1 -888-232-6348    cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position
of the U.S. Centers for Disease Control and Prevention.
Thank you

Summary: Maternal/Pediatric Respiratory Syncytial Virus (RSV)  Work Group Jefferson Jones MD MPH FAAP Co-Lead, Maternal/Pediatric RSV Work Group   Presenting on behalf of  Helen Chu, MD, MPH Chair, Maternal/Pediatric RSV Work Group   ACIP Meeting April 16, 2025 1U.S. Centers for Disease Control and Prevention  CDC and ACIP recommend all infants should be protected against  severe RSV disease with either maternal RSV vaccine or nirsevimab Maternal vaccine Abrysvo , Pfizer   *Either  maternal RSV…