Design, display and immunogenicity of HIV1 gp120 fragment immunogens on virus-like particles

Purwar, Mansi and Pokorski, Jonathan K and Singh, Pranveer and Bhattacharyya, Sanchari and Arendt, Heather and DeStefano, Joanne and La Branche, Celia C and Montefiori, David C and Finn, MG and Varadarajan, Raghavan (2018) Design, display and immunogenicity of HIV1 gp120 fragment immunogens on virus-like particles. In: VACCINE, 36 (42). pp. 6345-6353.

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Abstract

The broadly neutralizing antibody against HIV-1, b12, binds to the CD4 binding site (CD4bs) on the outer domain (OD) of the gp120 subunit of HIV-1 Env. We have previously reported the design of an E. coli expressed fragment of HIV-1 gp120, b122a, containing about 70% of the b12 epitope with the idea of focusing the immune response to this structure. Since the b122a structure was found to be only partially folded, as assessed by circular dichroism and protease resistance, we attempted to stabilize it by the introduction of additional disulfide bonds. One such mutant, b122a1-b showed increased stability and bound b12 with 30-fold greater affinity as compared to b122a. Various b122a and OD fragment proteins were displayed on the surface of Qp virus-like particles. Sera raised against these particles in six-month long rabbit immunization studies could neutralize Tier1 viruses across different subtypes with the best results observed with b122a1-b displayed particles. Significantly higher amounts of antibodies directed towards the CD4bs were also elicited by particles displaying b122a1-b. This study highlights the ability of fragment immunogens to focus the antibody response to the conserved CD4bs of HIV-1. (C) 2018 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Publication:	VACCINE
Publisher:	ELSEVIER SCI LTD
Additional Information:	Copy right for this article belong to ELSEVIER SCI LTD
Keywords:	Protein stability; Immune focusing; Neutralizing antibodies; Vaccine; Nanoparticles
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	14 Nov 2018 15:11
Last Modified:	14 Nov 2018 15:11
URI:	http://eprints.iisc.ac.in/id/eprint/61056

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