Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine
| Autor: | Fourati, Slim, Ribeiro, Susan Pereira, Blasco Tavares Pereira Lopes, Filipa, Talla, Aarthi, Lefebvre, Francois, Cameron, Mark, Kaewkungwal, J., Pitisuttithum, P., Nitayaphan, S., Rerks-Ngarm, S., Kim, Jerome H., Thomas, Rasmi, Gilbert, Peter B., Tomaras, Georgia D., Koup, Richard A., Michael, Nelson L., McElrath, M. Juliana, Gottardo, Raphael, Sékaly, Rafick-Pierre |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
AIDS Vaccines
Antigen Presentation Interferon Regulatory Factor-7 Science NF-kappa B env Gene Products Human Immunodeficiency Virus HIV Infections HIV Antibodies Mechanistic Target of Rapamycin Complex 1 Article Immunoglobulin A Placebos Interferon-gamma Immunoglobulin G Interferon Type I HIV-1 Humans Immunization lcsh:Q lcsh:Science |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. The RV144 vaccine trial showed reduced risk of HIV-1 acquisition, but mechanisms underlying protection are poorly understood. Here, Fourati et al. assess the transcriptomic profile of blood collected from 223 vaccinees and 40 placebo recipients and identify IRF7 as a mediator of protection. |
| Databáze: | OpenAIRE |
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