Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1.

Published online

Journal Article

The aim of this work was to start collecting information on rational combination of antibody (Ab) and T cell vaccines into single regimens. Two promising candidate HIV-1 vaccine strategies, sequential isolates of CH505 virus Envs developed for initiation of broadly neutralizing antibody lineages and conserved-mosaic tHIVconsvX immunogens aiming to induce effective cross-clade T cell responses, were combined to assess vaccine interactions. These immunogens were delivered in heterologous vector/modality regimens consisting of non-replicating simian (chimpanzee) adenovirus ChAdOx1 (C), non-replicating poxvirus MVA (M), and adjuvanted protein (P). Outbred CD1-SWISS mice were vaccinated intramuscularly using either parallel CM8M (tHIVconsvX)/CPPP (CH505) or sequential CM16M (tHIVconsvX)/CPPP (CH505) protocols, the latter of which delivered T cell CM prior to the CH505 Env. CM8M (tHIVconsvX) and CPPP or CMMP (CH505) vaccinations alone were included as comparators. The vaccine-elicited HIV-1-specific trimer-binding and neutralizing Abs and CD8+/CD4+ T cell responses induced by the combined and comparator regimens were not statistically separable among regimens. The Ab-lineage immunogen strategy was particularly suited for combined regimens for its likely less potent induction of Env-specific T cell responses relative to homologous epitope-based vaccine strategies. These results inform design of the first rationally combined Ab and T cell vaccine regimens in human volunteers.

Full Text

Duke Authors

Cited Authors

  • Wee, EG; Moyo, NA; Saunders, KO; LaBranche, C; Donati, F; Capucci, S; Parks, R; Borthwick, N; Hannoun, Z; Montefiori, DC; Haynes, BF; Hanke, T

Published Date

  • September 13, 2019

Published In

Volume / Issue

  • 14 /

Start / End Page

  • 148 - 160

PubMed ID

  • 31367651

Pubmed Central ID

  • 31367651

International Standard Serial Number (ISSN)

  • 2329-0501

Digital Object Identifier (DOI)

  • 10.1016/j.omtm.2019.06.003

Language

  • eng

Conference Location

  • United States