Important note: Information in this article was accurate in April 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, April 12, 1999
Daniel J. DeNoon, Senior Editor
The most successful candidate HIV vaccine approaches at eliciting anti-HIV antibodies use the so-called prime/boost technique. This approach begins with one or two priming immunizations with a virus-vectored (e.g., canarypox) or DNA-plasmid vaccine followed by booster immunizations with recombinant HIV envelope (Env) protein.
Now Philippe Lena and colleagues at the University of California, Davis, report that monkeys vaccinated with a DNA prime/protein boost SIV vaccine did far worse than animals immunized in a DNA prime/DNA boost regimen. "The group of animals boosted with recombinant Env protein showed increased viral loads and early progression to disease," the researchers reported. "Increased levels of antibodies correlated with aggravated infection." Lena et al. reported their findings in a poster presentation to the Second Annual Conference on Vaccine Research, held March 28-30 in Bethesda, Maryland. The study protocol called for monkeys to receive various prototype AIDS vaccines comprised of different forms of plasmid DNA-expressed simian immunodeficiency virus (SIV) envelope antigens. One group of animals then was boosted with recombinant Env (DNA/protein), and the other was boosted with noninfectious proviral DNA expressing the SIV Gag protein (DNA/DNA). All animals subsequently were challenged with the highly pathogenic SIVmac251.
In the DNA/DNA group, two animals resisted challenge infection and another had transient low viremia. Another two animals showed what the Lena et al. dubbed a "prolonged viral clearance phenomenon" in which there was a decay in HIV replication kinetics. "This decay has a half-life of two weeks; the viral load is reduced 500- to 1000-fold from the acute peak three months after infection and reaches undetectable levels later," they reported. "Similar decay kinetics are observed in AIDS patients undergoing HAART [highly active antiretroviral therapy]."
A far different picture emerged in the DNA/protein group. These animals developed much more pronounced humoral responses to vaccination, but had a far worse clinical response to infection. Lena et al. suggested that their findings have important implications for AIDS vaccine development.
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