Lessons from a multisite international trial in the Caribbean and South America of an HIV-1 Canarypox vaccine (ALVAC-HIV vCP1452) with or without boosting with MN rgp120.
(Clinical Trial;Journal Article;Multicenter Study)
BACKGROUND: The first multicenter, international National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored HIV vaccine trial took place in Brazil, Haiti, Peru and Trinidad. This randomized, double-blind, placebo-controlled, phase 2 trial evaluated the safety and immunogenicity of a clade B-derived, live canarypox HIV vaccine, vCP1452. vCP1452 was administered alone or with a heterologous boost of MN rgp120 glycoprotein. The trial was pivotal in deciding whether these vaccines advanced to phase 3 efficacy trials. METHODS: Forty seronegative volunteers per site were randomized to ALVAC alone, ALVAC plus MN rgp120, or placebo in a 0, 1, 3, and 6 month schedule. Immunogenicity was assayed by chromium-release cytotoxic T lymphocyte (CTL) responses; interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays (ELISpot); lymphocyte proliferation assays (LPA); neutralization; and enzyme-linked immunosorbent assays (ELISA). RESULTS: Enrollment and follow-up were excellent. Both vaccines were well tolerated. Neutralizing antibody to the laboratory-adapted MN strain was detected. Cellular immune responses, as measured by CTL, ELISpot, and LPA, did not differ between vaccines and placebos. CONCLUSIONS: The observation of disappointing immunogenicity in this and a parallel domestic study has informed future vaccine development. Equally important, challenges to doing an integrated trial across countries, cultures, languages, and differing at-risk populations were overcome. The identification of specific safety, ethical, logistic, and immunological issues in this trial established the foundation for current larger international studies.
Cleghorn, F; Pape, JW; Schechter, M; Bartholomew, C; Sanchez, J; Jack, N; Metch, BJ; Hansen, M; Allen, M; Cao, H; Montefiori, DC; Tomaras, GD; Gurunathan, S; Eastman, DJ; do Lago, RF; Jean, S; Lama, JR; Lawrence, DN; Wright, PF; 026 Protocol Team and the NIAID HIV Vaccine Trials Network,
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