A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses.

Autor: Cohen KW; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., De Rosa SC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Fulp WJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., deCamp AC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Fiore-Gartland A; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Mahoney CR; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Furth S; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Donahue J; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Whaley RE; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Ballweber-Fleming L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Seese A; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Schwedhelm K; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Geraghty D; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Finak G; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Menis S; IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92307, USA.; Center for HIV/AIDS Vaccine Development, Scripps Research Institute, La Jolla, CA 92307, USA.; Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92307, USA., Leggat DJ; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA., Rahaman F; IAVI, 125 Broad Street, 9th Floor, New York, NY 10004, USA., Lombardo A; IAVI, 125 Broad Street, 9th Floor, New York, NY 10004, USA., Borate BR; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Philiponis V; IAVI, 125 Broad Street, 9th Floor, New York, NY 10004, USA., Maenza J; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.; Department of Medicine, University of Washington, Seattle, WA 98195, USA., Diemert D; Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington DC, 20052, USA.; Department of Medicine, School of Medicine and Health Sciences, George Washington University, Washington DC 20052, USA., Kolokythas O; Department of Radiology, University of Washington, Seattle, WA 98195, USA., Khati N; Department of Radiology, School of Medicine and Health Sciences, George Washington University, Washington DC 20052, USA., Bethony J; Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington DC, 20052, USA., Hyrien O; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA., Laufer DS; IAVI, 125 Broad Street, 9th Floor, New York, NY 10004, USA., Koup RA; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA., McDermott AB; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA., Schief WR; IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92307, USA.; Center for HIV/AIDS Vaccine Development, Scripps Research Institute, La Jolla, CA 92307, USA.; Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92307, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA., McElrath MJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.; Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2023 May 24; Vol. 15 (697), pp. eadf3309. Date of Electronic Publication: 2023 May 24.
DOI: 10.1126/scitranslmed.adf3309
Abstrakt: The engineered outer domain germline targeting version 8 (eOD-GT8) 60-mer nanoparticle was designed to prime VRC01-class HIV-specific B cells that would need to be matured, through additional heterologous immunizations, into B cells that are able to produce broadly neutralizing antibodies. CD4 T cell help will be critical for the development of such high-affinity neutralizing antibody responses. Thus, we assessed the induction and epitope specificities of the vaccine-specific T cells from the IAVI G001 phase 1 clinical trial that tested immunization with eOD-GT8 60-mer adjuvanted with AS01 B . Robust polyfunctional CD4 T cells specific for eOD-GT8 and the lumazine synthase (LumSyn) component of eOD-GT8 60-mer were induced after two vaccinations with either the 20- or 100-microgram dose. Antigen-specific CD4 T helper responses to eOD-GT8 and LumSyn were observed in 84 and 93% of vaccine recipients, respectively. CD4 helper T cell epitope "hotspots" preferentially targeted across participants were identified within both the eOD-GT8 and LumSyn proteins. CD4 T cell responses specific to one of these three LumSyn epitope hotspots were observed in 85% of vaccine recipients. Last, we found that induction of vaccine-specific peripheral CD4 T cells correlated with expansion of eOD-GT8-specific memory B cells. Our findings demonstrate strong human CD4 T cell responses to an HIV vaccine candidate priming immunogen and identify immunodominant CD4 T cell epitopes that might improve human immune responses either to heterologous boost immunogens after this prime vaccination or to other human vaccine immunogens.
Databáze: MEDLINE
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