1区 · 医学
Article
作者: Leggat, David J ; McElrath, M Juliana ; deCamp, Allan C ; Rahaman, Farhad ; Hyrien, Ollivier ; De Rosa, Stephen C ; Lombardo, Angela ; Fulp, William J ; Menis, Sergey ; Schief, William R ; Fiore-Gartland, Andrew ; Laufer, Dagna S ; Borate, Bhavesh R ; Furth, Sarah ; Mahoney, Celia R ; Diemert, David ; Bethony, Jeffrey ; Koup, Richard A ; Maenza, Janine ; Khati, Nadia ; McDermott, Adrian B ; Seese, Aaron ; Geraghty, Daniel ; Philiponis, Vincent ; Donahue, Josh ; Cohen, Kristen W ; Schwedhelm, Katharine ; Whaley, Rachael E ; Kolokythas, Orpheus ; Finak, Greg ; Ballweber-Fleming, Lamar
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.