A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses
Science translational medicine
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. 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.
Cohen, Kristen W.; De Rosa, Stephen C.; Fulp, William J.; deCamp, Allan C.; Fiore-Gartland, Andrew; Mahoney, Celia R.; Furth, Sarah; Donahue, Josh; Whaley, Rachael E.; Ballweber-Fleming, Lamar; Seese, Aaron; Schwedhelm, Katharine; Geraghty, Daniel; Finak, Greg; Menis, Sergey; Leggat, David J.; Rahaman, Farhad; Lombardo, Angela; Borate, Bhavesh R.; Philiponis, Vincent; Maenza, Janine; Diemert, David; Kolokythas, Orpheus; Khati, Nadia; Bethony, Jeffrey; Hyrien, Ollivier; Laufer, Dagna S.; Koup, Richard A.; McDermott, Adrian B.; Schief, William R.; and McElrath, M Juliana, "A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses" (2023). GW Authored Works. Paper 2858.
Microbiology, Immunology, and Tropical Medicine