Vaccine-induced gene expression signature correlates with protection against SIV and HIV in multiple trials

Two independent preclinical non-human primate (NHP) challenge studies have showed partial efficacy with a mosaic Adenovirus 26 (Ad26)-based HIV-1 vaccine candidate. To investigate the basis of this protection, whole transcriptomics profiling by RNA sequencing was performed in sorted lymphocytes from samples at different time points after vaccination but prior to challenge. A transcriptional signature in B cells that associated with protection from acquisition was observed in both studies. The same gene expression signature was also observed to associate with protection in the only human vaccine trial that previously showed efficacy, and in two additional NHP studies evaluating the same canarypox based vaccine regimens. In the Ad26-based vaccine regimens strong antibody responses were elicited, and genes from the signature for which expression was enriched specifically associated with higher magnitude of functional antibody responses. The signature identified may be a broad and generalizable indicator of effective vaccination against viruses, as it was originally defined in clinical studies of influenza and yellow fever vaccines. This study represents an approach to gene expression analyses focused on phenotypic effect, and identifies genes that correlate with vaccine function and HIV/SIV acquisition.