Research ArticleHIV

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

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Science Translational Medicine  28 Aug 2019:
Vol. 11, Issue 507, eaaw4236
DOI: 10.1126/scitranslmed.aaw4236

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A proxy for protection

Current vaccines for HIV and simian immunodeficiency virus (SIV) offer only partial protection, and better vaccine candidates are much needed. Ehrenberg et al. found a gene expression signature that correlated with protection against SIV and HIV infection across multiple vaccine trials, using different vaccine regimens, in both nonhuman primates and humans. The identified signature comprised gene expression changes related to the B cell activation required for an effective immune response. This gene expression signature might be useful to evaluate which vaccine candidates may offer greater protection against HIV.


Current HIV vaccines are only partially efficacious, presenting an opportunity to identify correlates of protection and, thereby, potential insight into mechanisms that prevent HIV acquisition. Two independent preclinical challenge studies in nonhuman primates (NHPs) previously showed partial efficacy of a mosaic adenovirus 26 (Ad26)–based HIV-1 vaccine candidate. To investigate the basis of this protection, we performed whole transcriptomics profiling by RNA sequencing (RNA-seq) in sorted lymphocytes from peripheral blood samples taken during these studies at different time points after vaccination but before challenge. We observed a transcriptional signature in B cells that associated with protection from acquisition of simian immunodeficiency virus (SIV) or the simian-human immunodeficiency virus (SHIV) in both studies. 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 same gene expression signature also associated with protection in RV144 in the only human HIV vaccine trial to date that has shown efficacy and in two additional NHP studies that evaluated similar canarypox-based vaccine regimens. A composite gene expression score derived from the gene signature was one of the top-ranked correlates of protection in the NHP vaccine studies. This study aims to bridge preclinical and clinical data with the identification of a gene signature in B cells that is associated with protection from SIV and HIV infection by providing a new approach for evaluating future vaccine candidates.

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