A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants

• Published in: PloS one 2013-10, Vol.8 (10), p.e78289-e78289
• Main Authors: Afolabi, Muhammed O, Ndure, Jorjoh, Drammeh, Abdoulie, Darboe, Fatoumatta, Mehedi, Shams-Rony, Rowland-Jones, Sarah L, Borthwick, Nicola, Black, Antony, Ambler, Gwen, John-Stewart, Grace C, Reilly, Marie, Hanke, Tomáš, Flanagan, Katie L
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adults; AIDS; AIDS Vaccines - immunology; Antibody Formation - immunology; Antiretroviral agents; Antiretroviral therapy; Babies; Breast Feeding; Breast milk; Breastfeeding & lactation; Children & youth; Clinical trials; Councils; Deoxyribonucleic acid; Departments; Diphtheria; Disease transmission; DNA; Drug therapy; Enzyme-linked immunosorbent assay; Epidemiology; Feasibility studies; Female; Gambia; Genetic Vectors - genetics; Genetic Vectors - immunology; Health risks; Hepatitis; Hepatitis B; HIV; HIV Infections - immunology; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immunization; Immunization, Secondary - methods; Immunogenicity; Infant; Infants; Infections; Interference; Interferon; Interferon-gamma - immunology; Lymphocytes; Lymphocytes B; Male; Medical research; Medicine; Milk; Milk, Human - immunology; Milk, Human - virology; Mothers; Pediatrics; Pertussis; Safety; Tetanus; Transgenes; Tuberculosis; Vaccination - methods; Vaccines; Vaccines, DNA - immunology; Vaccinia virus - genetics; Vaccinia virus - immunology; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0078289

A vaccine to decrease transmission of human immunodeficiency virus type 1 (HIV-1) during breast-feeding would complement efforts to eliminate infant HIV-1 infection by antiretroviral therapy. Relative to adults, infants have distinct immune development, potentially high-risk of transmission when exposed to HIV-1 and rapid progression to AIDS when infected. To date, there have been only three published HIV-1 vaccine trials in infants. We conducted a randomized phase I clinical trial PedVacc 001 assessing the feasibility, safety and immunogenicity of a single dose of candidate vaccine MVA.HIVA administered intramuscularly to 20-week-old infants born to HIV-1-negative mothers in The Gambia. Infants were followed to 9 months of age with assessment of safety, immunogenicity and interference with Expanded Program on Immunization (EPI) vaccines. The trial is the first stage of developing more complex prime-boost vaccination strategies against breast milk transmission of HIV-1. From March to October 2010, 48 infants (24 vaccine and 24 no-treatment) were enrolled with 100% retention. The MVA.HIVA vaccine was safe with no difference in adverse events between vaccinees and untreated infants. Two vaccine recipients (9%) and no controls had positive ex vivo interferon-γ ELISPOT assay responses. Antibody levels elicited to the EPI vaccines, which included diphtheria, tetanus, whole-cell pertussis, hepatitis B virus, Haemophilus influenzae type b and oral poliovirus, reached protective levels for the vast majority and were similar between the two arms. A single low-dose of MVA.HIVA administered to 20-week-old infants in The Gambia was found to be safe and without interference with the induction of protective antibody levels by EPI vaccines, but did not alone induce sufficient HIV-1-specific responses. These data support the use of MVA carrying other transgenes as a boosting vector within more complex prime-boost vaccine strategies against transmission of HIV-1 and/or other infections in this age group. ClinicalTrials.gov NCT00982579. The Pan African Clinical Trials Registry PACTR2008120000904116.