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Modeling partially effective HIV vaccines in vitro.

Abstract
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.
AuthorsRohan John, Silvio Arango-Jaramillo, Steve Self, David H Schwartz
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 189 Issue 4 Pg. 616-23 (Feb 15 2004) ISSN: 0022-1899 [Print] United States
PMID14767814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • AIDS Vaccines
Topics
  • AIDS Vaccines (administration & dosage, pharmacology)
  • Disease Susceptibility
  • HIV-1 (drug effects, growth & development, isolation & purification)
  • Humans
  • Odds Ratio
  • Reference Values
  • Virus Replication (drug effects)

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