Modeling partially effective HIV vaccines in vitro.
Significant public health benefits could be realized with human immunodeficiency virus (HIV) vaccines that are incompletely effective. However, standard assays of experimental HIV vaccine immunogenicity may not correlate with antiviral effectiveness and cannot identify subtle effects. We developed an in vitro challenge assay (IVCA) that measures the net antiviral effect in whole peripheral blood mononuclear cells (PBMCs) to any titered HIV isolate. We then modeled partially effective postvaccination immune status 4 ways: use of PBMCs from highly exposed, uninfected individuals; depletion and partial reconstitution of autologous CD8+ cells from PBMCs from HIV-positive long-term nonprogressors; partial blocking of infection with chemokines; and variation in challenge virus dose. IVCA could detect as little as 3-fold differences in the challenge titer (30, 10, and 3 50% tissue-culture infective doses) or odds ratio of HIV infection. This robust and simple assay should be useful in determining which HIV vaccine candidates are suitable for field trials of efficacy.
John
Rohan
R
Department of Molecular Microbiology and Immunology, The Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Arango-Jaramillo
Silvio
S
Self
Steve
S
Schwartz
David H
DH
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000494:pharmacology*; D004198:Disease Susceptibility; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D006801:Humans; D016017:Odds Ratio; D012016:Reference Values; D014779:Virus Replication / Q000187:drug effects
D016915:AIDS Vaccines