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Mol Ther Methods Clin Dev. 2019 Jun 29;14:148-160. doi: 10.1016/j.omtm.2019.06.003. eCollection 2019 Sep 13.

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

Author information

1
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK.
2
Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
3
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
4
Department of Medicine and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
5
International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan.

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+/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.

KEYWORDS:

CH505; Conserved mosaic; EnvSeq1; HIV vaccine; MVA; T cell vaccine; broadly neutralizing antibodies; conserved regions; simian adenovirus; tHIVconsvX

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