ABSTRACT
BACKGROUND: adenoviruses are among the most promising vectors for the development of an HIV vaccine. The results of the phase IIB study of the adenovirus serotype 5-based Merck Trivalent HIV vaccine have raised the concern that serological immunity to adenovirus serotype 5 (Ad5) could be linked to HIV acquisition risk in high-risk individuals. We examined the association between adenovirus serostatus and the rate of incident HIV infection in populations at elevated risk of HIV acquisition. METHODS: we performed a nested case-control study of Ad5 serostatus among 299 HIV-infected and 590 matched HIV-uninfected persons participating in the Multicenter AIDS Cohort Study (MACS) and in HPTN 039, a study of herpes simplex virus 2 suppression among adults in the United States, South America, and Africa. Appropriate HIV cases and controls were identified in each cohort, and Ad5-neutralizing antibody titers were compared in these two groups. RESULTS: in MACS and HPTN 039, the relative risks of incident HIV infection among Ad5-seropositive vs. Ad5-seronegative individuals were 1.1 (95% confidence interval 0.8-1.5, P = 0.57) and 1.0 (95% confidence interval 0.4-2.3, P = 0.99), respectively. HIV-1 acquisition rates did not vary significantly by Ad5-neutralizing antibody titer. CONCLUSION: the presence of Ad5-neutralizing antibodies is not linked to the risk of HIV acquisition among populations at elevated risk of HIV infection.
Subject(s)
AIDS Vaccines/immunology , Adenoviridae Infections/immunology , Adenoviruses, Human/immunology , Antibodies, Neutralizing/immunology , HIV Seropositivity/immunology , HIV-1/pathogenicity , AIDS Vaccines/blood , Adenoviridae Infections/blood , Adenoviridae Infections/genetics , Adenoviruses, Human/genetics , Adult , Africa , Antibodies, Neutralizing/blood , Case-Control Studies , Female , Genetic Vectors , Humans , Male , Risk Assessment , South America , United StatesABSTRACT
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.