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Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1.
- Source :
-
Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2019 Jun 29; Vol. 14, pp. 148-160. Date of Electronic Publication: 2019 Jun 29 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- 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 <superscript>+</superscript> /CD4 <superscript>+</superscript> 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.
Details
- Language :
- English
- ISSN :
- 2329-0501
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- Molecular therapy. Methods & clinical development
- Publication Type :
- Academic Journal
- Accession number :
- 31367651
- Full Text :
- https://doi.org/10.1016/j.omtm.2019.06.003