Back in 2012, a paper describing a study of a novel vaccine approach in the SIV/macaque model was published to little fanfare in the open access journal Cell Reports. The brainchild of researcher Jean-Marie Andrieu, the idea behind the vaccine was to turn the traditional approach to immunization on its head: the aim was to suppress the response to SIV, thereby depriving the virus of the activated CD4 T cell targets that normally fuel viral replication. A probiotic, Lactobacillus plantarum, was used to deliver SIV antigens to the gut with the goal of inducing SIV-specific immune tolerance. Macaques were then challenged with pathogenic SIV. The results were surprising and unprecedented: 15 out of 16 animals resisted infection. Protection was associated with the induction of SIV-specific CD8 T cells displaying a regulatory, immune-suppressive phenotype.
The work finally garnered significant media attention in 2014 when a follow-up paper was published in Frontiers in Immunology, leading to articles in the Washington Post and on the AIDSMap website. Prominent scientist and HIV vaccine advocate José Esparza co-authored a commentary highlighting the results and the Bill & Melinda Gates Foundation funded an independent confirmatory study by the research group of Guido Silvestri at Emory University.
In a presentation at the Cent Gardes Conference last fall—that has so far received as little publicity as the original Cell Reports paper—Silvestri debuted preliminary results, revealing that the vaccine has shown no protective efficacy, either in terms of preventing infection or reducing post-infection viral loads. A total of seventeen macaques received the vaccine, and sixteen became infected. In comparison, out of seventeen controls, fifteen became infected. Andrieu cooperated with the independent evaluation and supplied the vaccine for the study. Silvestri noted that the only differences between the experiments were the origin of the macaques (Indian vs. Chinese) and the use of a SIVmac239 challenge virus from a different stock; neither seems likely to explain the dramatic divergence in outcomes. A webcast of Silvestri’s talk is available on the Global HIV/AIDS Vaccine Enterprise website (along with the entire Cent Gardes proceedings). The results will almost certainly be subject to further analysis and debate when they are published.
Acknowledgement: many thanks to Robert Reinhard for bringing Silvestri’s presentation to my attention.
UPDATE: Nicolas Vabret (@neoviral on Twitter) pointed out to me that Andrieu and colleagues mention Silvestri's findings in the discussion section of a recent paper in Frontiers in Immunology, and suggest that they may be explained by differences in MHC between macaques of different geographic origin. I'm not sure how plausible this explanation might be given how starkly the results differed between experiments, but there are studies reporting that Mamu-B alleles are largely distinct in macaques of Chinese and Indian origin.