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.

Journal Article (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.

Full Text

Duke Authors

Cited Authors

  • 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,

Published Date

  • October 1, 2007

Published In

Volume / Issue

  • 46 / 2

Start / End Page

  • 222 - 230

PubMed ID

  • 17693888

International Standard Serial Number (ISSN)

  • 1525-4135

Digital Object Identifier (DOI)

  • 10.1097/QAI.0b013e318149297d


  • eng

Conference Location

  • United States