Safety and Immunogenicity Study of Candidate HIV-1 Vaccine Given to Healthy Infants Born to HIV-1-infected Mothers

Study Overview
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Brief Summary
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Objectives: Primary: Safety and immunogenicity of MVA.HIVA vaccine in 20-week-old healthy Kenyan infants born to HIV-1-infected mothers. Secondary: HIV-1 immunogenicity comparison between MVA.HIVA and age-matched unvaccinated control arms in each cohort (breastfeeding or formula feeding) HIV-1 immunogenicity comparison between breastfeeding and formula feeding infants receiving MVA.HIVA HIV-1 immunogenicity comparison between breastfeeding and formula feeding infants in the age-matched unvaccinated control group Comparison of responses to certain Kenyan Extended Programme on Immunization (KEPI) vaccines (OPV, DTP, HBV, and HiB) between MVA.HIVA versus age-matched unvaccinated controls in each cohort, between breast versus formula feeding infants in the age-matched unvaccinated control group, and between breast versus formula infants receiving MVA.HIVA Comparison of immune activation and phenotypic profile of lymphocytes between breast and formula feeding infants in each cohort (MVA.HIVA and age-matched unvaccinated control) Build capacity for Infant HIV-1 Vaccine Clinical Trials Centre in Nairobi, Kenya.

Official Title
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An Open Randomized Phase I/II Study Evaluating Safety and Immunogenicity of a Candidate HIV-1 Vaccine, MVA.HIVA, Administered to Healthy Infants Born to HIV-1-infected Mothers

Conditions
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HIV-1, HIV Infections

Intervention / Treatment
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* Biological: MVA.HIVA


Participation Criteria
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Eligibility Criteria
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Infant Inclusion Criteria Healthy infants < 3 days of age (day of birth = Day 0) at enrolment Birth weight > 2500 grams Born to an eligible woman Written informed consent by parent Infant Exclusion Criteria HIV infection, as determined by a filter paper and/or RNA test prior to vaccination. Participation in any other HIV-1 vaccine or drug trial. Failure to receive all standard KEPI immunizations according to national immunization programme. Weight for age z-scores outside of 2 standard deviations of normal at the time of vaccination. Acute disease at the time of vaccination (acute disease is defined as the presence of a moderate or severe illness with or without fever). All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory tract infection with or without low-grade febrile illness, i.e., temperature of <37.5 °C). Axillary temperature of ≥ 37.5 °C at the time of vaccination. Any clinically significant abnormal finding on screening from biochemistry or haematology by the time of vaccination. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g., egg products. Presence of any underlying disease that compromises the diagnosis and evaluation of response to the vaccine. Any other on-going chronic illness requiring hospital specialist supervision. Administration of immunoglobulins and/or any blood products within one month preceding the planned administration of the vaccine candidate. Any history of anaphylaxis in reaction to vaccination. Research Physician's assessment of lack of willingness by parents to participate and comply with all requirements of the protocol, or identification of any factor felt to significantly increase the infant's risk of suffering an adverse outcome. Likelihood of travel away from the study area.

Ages Eligible for Study
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Maximum Age: 3 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccinees<br>18 breast-fed and 18 formula-fed infants at the age of 20 weeks | Biological: MVA.HIVA<br>* 1 dose of 5 x 10^7 pfu of MVA.HIVA administered intramuscularly<br>|
| No Intervention: Controls<br>18 breast-fed and 18 formula-fed infants at the age of 20 weeks | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For safety and reactogenicity: Actively and passively collected data on adverse events. |  | Up to 28 weeks after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For immunogenicity to KEPI vaccines: Antibody levels to specific vaccines as measured by ELISA. |  | 1 week before and 1 week after vaccination | 
| For immunogenicity to MVA.HIVA: Frequency of IFN-γ-producing cells determined in an ELISPOT assay after overnight stimulation with a pool of HIVA-derived peptides. |  | Up to 24 weeks after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Vaccine, MVA, PMTCT, HIV preventive vaccine, HIV seronegativity