Document text
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.