Evaluation of a Novel Multi-immunogen Vaccine Strategy for Targeting 4E10/10E8 Neutralizing Epitopes on HIV-1 Gp41 Membrane Proximal External Region

Overview

Journal Virology

Specialty Microbiology

Date 2017 Feb 27

PMID 28237764

Citations 8

Authors

Saikat Banerjee

Heliang Shi

Marisa Banasik

Hojin Moon

William Lees

Yali Qin

Andrew Harley

Adrian Shepherd

Michael W Cho

Affiliations

Soon will be listed here.

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-gp160). 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 (NWFDITNWLWYIK). 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.

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