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CD8+ cells key to HIV resistance among highly exposed uninfected subjects
  By Megan Rauscher
NEW YORK (Reuters Health) - Results of an in vitro study provide more evidence that CD8+ T cells play a major role in HIV-1 resistance among highly HIV exposed, persistently uninfected (EU) individuals. The findings, the investigators say, may help guide HIV vaccine development.
Specifically, Dr. David H. Schwartz said their experiments indicate that "immune-mediated resistance to HIV, such as that potentially induced by new HIV vaccines, will not be 'all-or-none,' but will show a spectrum of effectiveness among populations and against different levels of exposure."
Dr. Schwartz and colleagues used a newly developed in vitro challenge assay to better define the "magnitude, breadth, and CD8+ cell dependence of resistance" to HIV infection among 14 EU individuals with homozygous wild type CCR5 and normal, uninfected low-risk controls. This assay is capable of detecting modest levels of antiviral activity akin to that expected from first generation HIV vaccines, they explain.
They report that CD8+ cells were relatively increased in EU individuals compared with controls and played a "major role" in resistance from viral infection.
Resistance depended on the dose of virus inoculum and, importantly, Dr. Schwartz said, extended across HIV clades. This suggests that "it may not be necessary to tailor the vaccine product to strains of HIV circulating in each target population, as significant cross-clade protection is likely to be seen with any vaccine broadly effective against one of the major clades," he said.
Supporting prior studies in EU individuals, the team's experiments also show that decreased exposure to HIV through a reduction in high-risk behavior leads to decreased antiviral immunity. This suggests, Dr. Schwartz said, that "acquired immunity to HIV, whether through vaccination or natural exposure, is likely to wane over time without booster immunizations."
"These observations should inform the design of experimental vaccines and efficacy trials," the researchers write in the January 1st issue of The Journal of Acquired Immune Deficiency Syndromes.
J Acquir Immune Defic Syndr 2004;35:1-7.


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