B cell gene signature associated with protection efficacy in HIV vaccines

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In a new study published in Science Translational Medicine, a team of researchers led by The US Military HIV Research Program at the Walter Reed Army Institute of Research (MD, USA) discovered a transcriptional signature in B cells associated with protection from SIV or HIV infection in five independent trials of HIV-1 vaccine candidates.

In the HIV vaccine trial named RV144 – the only human trial that previously showed modest efficacy – the gene expression signature was discovered to correlate with protection.

Additionally, these specific genes and signature were previously shown to be induced in response to influenza and yellow fever vaccine.

“We think this B cell signature is a broad indicator of effective responses after vaccination and could potentially be used to help design effective vaccines against HIV and other pathogens,” commented Rasmi Thomas (The US Military HIV Research Program), senior author of the study.

After RNA sequencing data from preclinical HIV-1 vaccine candidate trials was examined, the team of researchers hypothesized that the partial efficacy observed could be due to variations in the expressions produced by the investigational vaccine. By using RNA sequencing methods they observed a common protective gene signature in the non-human primates.

The B cell signature that correlated with protection in the preclinical study and RV144 also correlated in two pox-protein vaccines in non-human primates. Furthermore, the same signature is associated with higher levels of functional antibody-dependent cellular phagocytosis, which could provide reason to why the vaccine was protective.

“We’re excited because the identified gene signature associates with protective efficacy for the two vaccine regimens that are currently being tested in [HIV] human efficacy trials in Africa, the Imbokodo study and HVTN702. This new correlate of protection provides a clue as to why the vaccines were partially protective previously and may help to understand the mechanisms of efficacy in these new studies,” concluded Thomas.

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Source: Ehrenberg PK, Shangguan S, Issac B et al. A vaccine-induced gene expression signature correlates with protection against SIV and HIV in multiple trials. Sci. Trans. Med. 11(507), eaaw4236 (2019); www.eurekalert.org/emb_releases/2019-08/tumh-nss082619.php


What are RNA sequencing methods?

RNA sequencing is a technique that is used to examine the presence and quantity of RNA in a given sample, using next-generation sequencing. Using RNA sequencing can allow an understanding of the transcriptome – the total cellular RNA contents – including mRNA, tRNA and rRNA and this technique is widely considered to be superior to previously used techniques, such as microarray hybridization.

Which HIV vaccines are currently in clinical trials?

Immune interventions to prevent HIV infection have yet to achieve success in humans; there have been a number of candidates that have been tested in clinical trials, however, few have seen any success. Currently, there are two parallel approaches to HIV vaccine discovery, first, improving upon and amplifying the RV144 trial, and second, developing immunogens that induce broadly neutralizing antibodies. The most recent clinical success was in July 2018 when a mosaic vaccine was reported to be well-tolerated and induced comparable and robust immune responses in healthy adults and rhesus monkeys in the APPROACH trial. However, the challenge of overcoming HIV sequence diversity and immune escape is formidable.

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