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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.

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


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.


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

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