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Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization

McCoy, LE; Quigley, AF; Strokappe, NM; Bulmer-Thomas, B; Seaman, MS; Mortier, D; Rutten, L; ... Weiss, RA; + view all (2012) Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization. The Journal of Experimental Medicine , 209 (6) pp. 1091-1103. 10.1084/jem.20112655. Green open access

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Abstract

Llamas (Lama glama) naturally produce heavy chain-only antibodies (Abs) in addition to conventional Abs. The variable regions (VHH) in these heavy chain-only Abs demonstrate comparable affinity and specificity for antigens to conventional immunoglobulins despite their much smaller size. To date, immunizations in humans and animal models have yielded only Abs with limited ability to neutralize HIV-1. In this study, a VHH phagemid library generated from a llama that was multiply immunized with recombinant trimeric HIV-1 envelope proteins (Envs) was screened directly for HIV-1 neutralization. One VHH, L8CJ3 (J3), neutralized 96 of 100 tested HIV-1 strains, encompassing subtypes A, B, C, D, BC, AE, AG, AC, ACD, CD, and G. J3 also potently neutralized chimeric simian-HIV strains with HIV subtypes B and C Env. The sequence of J3 is highly divergent from previous anti-HIV-1 VHH and its own germline sequence. J3 achieves broad and potent neutralization of HIV-1 via interaction with the CD4-binding site of HIV-1 Env. This study may represent a new benchmark for immunogens to be included in B cell-based vaccines and supports the development of VHH as anti-HIV-1 microbicides.

Type: Article
Title: Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1084/jem.20112655
Publisher version: http://dx.doi.org/10.1084/jem.20112655
Language: English
Additional information: This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Keywords: Animals, Antibodies, Neutralizing, Antibody Affinity, Antigens, CD4, Camelids, New World, Epitopes, HIV-1, Immunoglobulin Variable Region, Neutralization Tests, Peptide Library, Recombinant Proteins, Vaccines, DNA, env Gene Products, Human Immunodeficiency Virus
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/1357355
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