Evaluation of a novel multi-immunogen vaccine strategy for targeting 4E10/10E8 neutralizing epitopes on HIV-1 gp41 membrane proximal external region

Banerjee, S. and Shi, H. and Banasik, M. and Moon, H. and Lees, W. and Qin, Y. and Harley, A. and Shepherd, Adrian J. and Cho, M.W. (2017) Evaluation of a novel multi-immunogen vaccine strategy for targeting 4E10/10E8 neutralizing epitopes on HIV-1 gp41 membrane proximal external region. Virology 505 , pp. 113-126. ISSN 0042-6822.

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Official URL: https://doi.org/10.1016/j.virol.2017.02.015

Abstract

The membrane proximal external region (MPER) of HIV-1 gp41 is targeted by broadly neutralizing antibodies (bnAbs) 4E10 and 10E8. In this proof-of-concept study, we evaluated a novel multi-immunogen vaccine strategy referred to as Incremental, Phased Antigenic Stimulation for Rapid Antibody Maturation (IPAS-RAM) to induce 4E10/10E8-like bnAbs. Rabbits were immunized sequentially, but in a phased manner, with three immunogens that are progressively more native (gp41-28×3, gp41-54CT, and rVV-gp160DH12). Although nAbs were not induced, epitope-mapping analyses indicated that IPAS-RAM vaccination was better able to target antibodies towards the 4E10/10E8 epitopes than homologous prime-boost immunization using gp41-28×3 alone. MPER-specific rabbit monoclonal antibodies were generated, including 9F6. Although it lacked neutralizing activity, the target epitope profile of 9F6 closely resembled those of 4E10 and 10E8 (671NWFDITNWLWYIK683). B-cell repertoire analyses suggested the importance of co-immunizations for maturation of 9F6, which warrants further evaluation of our IPAS-RAM vaccine strategy using an improved priming immunogen.

Metadata

Item Type:	Article
Keyword(s) / Subject(s):	HIV-1, Vaccine, gp41, MPER, Rabbit, Neutralizing antibody, Antibody maturation, Next-generation sequencing, NGS
School:	Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
Research Centres and Institutes:	Data Analytics, Birkbeck Institute for
Depositing User:	Administrator
Date Deposited:	10 Mar 2017 14:09
Last Modified:	02 Aug 2023 17:32
URI:	https://eprints.bbk.ac.uk/id/eprint/18320

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