Safety and Immunogenicity of a Candidate HIV-1 Vaccine,MVA.HIVA, Administered to Healthy Gambian Infants Born to HIV-1/2-Uninfected Mothers

Abstract

Background: The development of a safe and effective HIV-1 vaccine remains a global priority especially in prevention of mother to child transmission of HIV-1 during breastfeeding. Our vaccine platform consists of recombinant BCG prime- recombinant modified vaccinia virus Ankara (MVA) boost. This study is the first stage and evaluates the safety and immunoge- nicity of MVA.HIVA, a candidate HIV-1 vaccine, among healthy Gambian infants born to HIV 1/2 uninfected mothers. Methods: Sixty-five mothers were sensitized on delivery of healthy babies at Sukuta Health Centre, The Gambia. Sixty-two of whom consented to HIV voluntary counseling and testing and all the mothers (100%) had negative HIV test. Forty-eight of the el- igible infants were randomized into vaccine and no-treatment control group at 20 weeks of age. The vaccine group received one dose of 5 · 10^7 pfu of MVA.HIVA administered intramuscu- larly. The safety of MVA.HIVA was determined by comparing adverse events, reactogenicity, biochemical and haematological data of vaccine and control groups. Immunogenicity was mea- sured by interferon (IFN)- c ELISPOT assay on peripheral blood mononuclear cells. Results: The mean Haemoglobin (Hb), White Blood Cell count (WBC), Alanine transaminase (ALT) and Creatinine at pre- vaccination and post–vaccination visits were within acceptable normal ranges. Adverse events observed included fever, ex- cessive crying, cough, vomiting, bilateral eye discharge, diar- rhea and poor weight gain. All study infants had negative HIV antibody tests at 28 weeks and no severe adverse events or suspected unexpected serious adverse reactions were reported. Preliminary cultured IFN- c ELISPOT analysis showed induc- tion of HIV-1-specific T-cell responses in about 40% of the vaccinees. Conclusion: We have shown that MVA.HIVA is safe and im- munogenic in healthy Gambian infants. A parallel study PedVacc002 of MVA.HIVA administered to infants born to HIV-1-positive mothers is ongoing in Kenya.