Important note: Information in this article was accurate in 2002. The state of the art may have changed since the publication date. TAGline - Volume 9 Issue 1 - January-February 2002
One interesting aspect of Merck's vaccine study appears to have escaped comment. The data comprised two sets of studies, one set evaluating the vaccine vectors given singly while the second set combined the DNA vector with either Ad5 or MVA in a prime-boost regimen. In the former studies, macaques were challenged with SHIV89.6P twelve weeks after the last immunization, while in the prime-boost the challenge was administered just six weeks after the booster shot. The data clearly demonstrates that the prime-boost approach induced larger T-cell responses than either the Ad5 or MVA vector given alone, but what about the post-challenge outcomes? Looking at the graphs, it appears that control of viral load and preservation of CD4+ T-cell counts was more consistent in the animals that received Ad5 and MVA alone compared to those that received prime-boost. So what's going on here?
The explanation may relate to a fundamental tenet of T-cell immunology. CTL maven Rafi Ahmed has long noted that vaccine-induced T-cell responses need to reach a "resting memory" state in order to respond optimally to a subsequent boost or challenge. The canonical T-cell response to a vaccine involves a peak of proliferation, followed by a "death phase" and ending with a stable but lower-level population of resting memory cells. It can take several weeks for this process to play out in mice, and how long it takes in higher primates is currently unclear. It is possible that for the macaques in the Merck study that received Ad5 or MVA alone, the additional six weeks of rest between the final immunization and challenge may explain the otherwise counterintuitive results. This will be a key question to explore in future animal studies, and, according to Emilio Emini, data is forthcoming that will address the question more directly. RJ
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