Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 30787294.
- Also identified by DOI 10.1038/s41467-019-08854-2 and PMC identifier 6382801.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The RV144 vaccine trial showed reduced risk of HIV-1 acquisition by 31.2%, although mechanisms that led to protection remain poorly understood. Here we identify transcriptional correlates for reduced HIV-1 acquisition after vaccination. We assess the transcriptomic profile of blood collected from 223 participants and 40 placebo recipients. Pathway-level analysis of HIV-1 negative vaccinees reveals that type I interferons that activate the IRF7 antiviral program and type II interferon-stimulated genes implicated in antigen-presentation are both associated with a reduced risk of HIV-1 acquisition. In contrast, genes upstream and downstream of NF-κB, mTORC1 and host genes required for viral infection are associated with an increased risk of HIV-1 acquisition among vaccinees and placebo recipients, defining a vaccine independent association with HIV-1 acquisition. Our transcriptomic analysis of RV144 trial samples identifies IRF7 as a mediator of protection and the activation of mTORC1 as a correlate of the risk of HIV-1 acquisition.
Medical subject headings
- AIDS Vaccines
- HIV Infections
- HIV-1
- Interferon Regulatory Factor-7
- Interferon Type I
- Interferon-gamma
- Mechanistic Target of Rapamycin Complex 1