Immunogenicity of Co-administered Yellow Fever and Measles, Mumps, and Rubella (MMR) Vaccines

Study Overview
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Brief Summary
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This study evaluates seroconversion against measles, mumps, rubella and yellow fever following vaccination. One-third of children will receive both yellow fever and measles, mumps, and rubella (MMR) vaccines on the same day; one- third of children will receive MMR vaccine at enrollment followed by yellow fever vaccine 4 weeks later; one-third of children will receive yellow fever vaccine at enrollment followed by MMR vaccine 4 weeks later.

Detailed Description
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The World Health Organization (WHO) and the Pan American Health Organization recommend that yellow fever and measles, mumps and rubella (MMR) vaccines be administered on the same day or at least 4 weeks apart to prevent interference between live vaccines. In 2011 a Brazilian study demonstrated lower seroconversion against yellow fever, rubella, and mumps when the two vaccines were administered on the same day compared with administering them separately. WHO urged that additional studies be conducted to examine this issue. This Phase IV study aims to determine if seroconversion against measles, mumps, rubella, and yellow fever after administration of MMR and yellow fever vaccines on the same day is non-inferior to seroconversion after sequential administration 28 days apart in health 12-month old children.

Official Title
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Immunogenicity of Co-administered Yellow Fever and Measles, Mumps, and Rubella (MMR) Vaccines in Children Under 2 Years Old in Argentina

Conditions
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Vaccine Response Impaired

Intervention / Treatment
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* Biological: Co-administration of MMR/YF
* Biological: MMR followed by YF
* Biological: YF followed by MMR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 12 to 24 months at the time of enrollment Healthy child, determined by clinical history Availability to do study visits and blood sampling on days 28 + 7 and 56 + 14 Informed consent signed by parents Exclusion Criteria: Previous vaccination against yellow fever, measles, mumps, or rubella History of yellow fever, measles, mumps or rubella Contraindication for any of the study vaccines: yellow fever vaccine or triple viral vaccine, including: Allergy to eggs, gelatin, or neomycin Weakened immunological function, including HIV infection, primary immunodeficiencies, having received immunosuppressive doses of oral or injectable corticosteroids (or equivalent), having received immunomodulators or chemotherapeutic agents Thymus disease Serious illness/fever (mild illness without fever is not an exclusion criterion) Administration of immunoglobulins or other blood derivative within 6 months of enrollment in the study or during the study a. Exception: children with a history of Kawasaki disease who received gammaglobulin cannot be enrolled if they received it in the previous 11 months. Administration of any other attenuated viral vaccine (i.e., for chickenpox) in the month prior to enrollment, or if the administration of any other attenuated viral vaccine is expected during the study (up to 3 months) Not being available for the entire study period (up to 3 months), or not able to make the scheduled visits or complete the study procedures Participating in another clinical drug trial of a drug, vaccine, or medical device Any condition that, in opinion of the study staff, represents a health risk to the participant or interferes with the evaluation of the response to the vaccine (i.e., children in percentile ≤ 3 in the height/weight tables will be considered undernourished and cannot be selected)

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Co-administration of MMR/YF<br>Participants randomized to this arm will receive both MMR and yellow fever vaccines on Day 0. | Biological: Co-administration of MMR/YF<br>* Both MMR & yellow fever vaccines administered on Day 0.<br>|
| Active Comparator: MMR followed by YF<br>Participants randomized to this arm will receive MMR vaccine on Day 0 followed by yellow fever vaccine on Day 28. | Biological: MMR followed by YF<br>* MMR vaccine administered on Day 0 and yellow fever vaccine administered on Day 28.<br>|
| Active Comparator: YF followed by MMR<br>Participants randomized to this arm will receive YF vaccine on Day 0 followed by MMR vaccine on Day 28. | Biological: YF followed by MMR<br>* Yellow fever vaccine administered on Day 0 and MMR vaccine administered on Day 28.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion after yellow fever vaccination using the plaque reduction neutralization test (PRNT). | PRNTs will be used to measure antibody titers for yellow fever. | 28-35 days post-vaccination | 
| Seroconversion after MMR vaccination using the ELISA method. | The ELISA method will be used to measure antibody titers for measles, mumps, and rubella. | 28-35 days post-vaccination. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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yellow fever vaccine, MMR vaccine, immunogenicity