The transcription factor CREB1 is a mechanistic driver of immunogenicity and reduced HIV-1 acquisition following ALVAC vaccination.

Autor: Tomalka JA; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Pelletier AN; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Fourati S; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Latif MB; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Sharma A; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Furr K; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Carlson K; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Lifton M; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Gonzalez A; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Wilkinson P; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Franchini G; Center for Cancer Research Vaccine Branch, National Cancer Institute NIH, Bethesda, MD, USA., Parks R; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Letvin N; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Yates N; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Seaton K; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Tomaras G; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Tartaglia J; Sanofi-Pasteur, Swiftwater, PA, USA., Robb ML; Military HIV Research Program, Henry Jackson Foundation and Walter Reed Army Institute for Research, Bethesda and Silver Spring, MD, USA., Michael NL; Military HIV Research Program, Henry Jackson Foundation and Walter Reed Army Institute for Research, Bethesda and Silver Spring, MD, USA., Koup R; Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA., Haynes B; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Santra S; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. ssantra@bidmc.harvard.edu., Sekaly RP; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. rafick.sekaly@emory.edu.; Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA. rafick.sekaly@emory.edu.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2021 Oct; Vol. 22 (10), pp. 1294-1305. Date of Electronic Publication: 2021 Sep 23.
DOI: 10.1038/s41590-021-01026-9
Abstrakt: Development of effective human immunodeficiency virus 1 (HIV-1) vaccines requires synergy between innate and adaptive immune cells. Here we show that induction of the transcription factor CREB1 and its target genes by the recombinant canarypox vector ALVAC + Alum augments immunogenicity in non-human primates (NHPs) and predicts reduced HIV-1 acquisition in the RV144 trial. These target genes include those encoding cytokines/chemokines associated with heightened protection from simian immunodeficiency virus challenge in NHPs. Expression of CREB1 target genes probably results from direct cGAMP (STING agonist)-modulated p-CREB1 activity that drives the recruitment of CD4 + T cells and B cells to the site of antigen presentation. Importantly, unlike NHPs immunized with ALVAC + Alum, those immunized with ALVAC + MF59, the regimen in the HVTN702 trial that showed no protection from HIV infection, exhibited significantly reduced CREB1 target gene expression. Our integrated systems biology approach has validated CREB1 as a critical driver of vaccine efficacy and highlights that adjuvants that trigger CREB1 signaling may be critical for efficacious HIV-1 vaccines.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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