V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity
Year: 2018
Type: article
Abstract: Antibodies that bind residue K169 in the V2 region of the HIV-1 envelope correlated with reduced risk of infection in the RV144 vaccine trial but were restricted to two ED-motif-encoding light chain genes. Here, we identify an HIV-infected donor with high-titer V2 peptide-binding antibodies and isolate two antibody lineages (CAP228-16H/19F and CAP228-3D) that mediate potent antibody-dependent cell-mediated cytotoxicity (ADCC). Both lineages use the IGHV5-51 heavy chain germline gene, similar to the RV144 antibody CH58, but one lineage (CAP228-16H/19F) uses a light chain without the ED motif. A cocrystal structure of CAP228-16H bound to a V2 peptide identified a IGLV3-21 gene-encoded DDxD motif that is used to bind K169, with a mechanism that allows CAP228-16H to recognize more globally relevant V2 immunotypes. Overall, these data further our understanding of the development of cross-reactive, V2-binding, antiviral antibodies and effectively expand the human light chain repertoire able to respond to RV144-like immunogens.
Source: Cell Reports
Authors: Charmaine van Eeden, Constantinos Kurt Wibmer, Cathrine Scheepers, Simone I. Richardson, Molati Nonyane, Bronwen Lambson, Nonhlanhla N. Mkhize, Balakrishnan Vijayakumar, Zizhang Sheng, Sherry Stanfield-Oakley, Jinal N. Bhiman, Valerie Bekker, Tandile Hermanus, Batsirai Mabvakure, Arshad Ismail, M. Anthony Moody, Kevin Wiehe, Nigel Garrett, Salim Abdool Karim, Heini Dirr, Manuel A. Fernandes, Yasien Sayed, Lawrence Shapiro, Guido Ferrari, Barton F. Haynes, Penny L. Moore, Lynn Morris
Institutions: National Health Laboratory Service, University of the Witwatersrand, National Institute for Communicable Diseases, Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, Duke University, Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: U.S. Department of Health and Human Services, National Research Foundation, South African Medical Research Council, Poliomyelitis Research Foundation, Department of Science and Technology, Philippines, Mauritius Research Council, Centro Nacional de Pesquisa em Energia e Materiais, Ministério da Ciência, Tecnologia, Inovações e Comunicações, National Institutes of Health, Medical Research Council, Science and Technology Facilities Council, National Institute of Allergy and Infectious Diseases, Fogarty International Center
Awards: COLLABORATIVE AIDS PROGRAMME OF RESEARCH IN SOUTH AFRICA, G1757274933, G1801948538, Columbia University-Southern African AIDS International Training/Research Program, G5946334740, GCRF - START: Synchrotron Techniques for African Research and Technology, Data commons for 'omic, microscopy and analysis core facilities, G6483709719, G7185013638, G90147455
OpenAlex ID: W2903937718