In the November 29, 2008 issue of Lancet, two reports (plus a commentary) report the famously disappointing outcome of a recent placebo-controlled study testing adenoviral vector-based vaccines against HIV. News reports over a year ago reported that the study was halted after an interim analysis failed to show any prospect of proving effective. More troubling, subgroup analysis suggested that vaccine recipients who had high pre-existing immunity to the adenoviral vectors showed higher rates of sero-conversion compared with placebo. As this vaccine was among the most promising and advanced in terms of development, these results were seen as a major setback.The recent Lancet reports paint a complicated picture: if I read them correctly, the inference that vector might enhance sero-conversion is muddied by the finding that circumcision status might also have played a role in sero-conversion (men with higher rates of adenoviral immunity were also, coincidentally, less likely to be circumcised).
What is clear, from what I gather, is that this is a good example where rigorous preclinical testing, coupled with rigorous trial design, permits meaningful interpretation of (unfortunately) negative human trial results. As Merlin Robb notes in a commentary accompanying the Lancet reports "the predictive value of the non-human SHIV-challenge model is not supported by this experience. The benchmarks for advancing candidate vaccines to efficacy testing and the priorities for vaccine research have been re-examined."
Well-designed studies, supported by rigorous preclinical testing, should always produce valuable, findings– like the unexpected "found figures" in the bark of a tree (photo credit: Readwalker, Found figures, 2006)
