1. 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.
- Author
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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, and Wright PF
- Subjects
- AIDS Vaccines administration & dosage, AIDS Vaccines blood, Adolescent, Adult, Brazil, Double-Blind Method, Female, HIV Antibodies blood, HIV Envelope Protein gp120 administration & dosage, HIV Envelope Protein gp120 blood, Haiti, Humans, Immunization Schedule, Immunization, Secondary, Injections, Intramuscular, Interferon-gamma analysis, Lymphocyte Activation, Male, Middle Aged, Neutralization Tests, Peru, T-Lymphocytes, Cytotoxic immunology, Treatment Outcome, Trinidad and Tobago, Vaccines, Synthetic administration & dosage, Vaccines, Synthetic blood, Vaccines, Synthetic immunology, AIDS Vaccines immunology, HIV Envelope Protein gp120 immunology, HIV Infections immunology, HIV-1, Vaccination
- Abstract
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.
- Published
- 2007
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