Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans
Year: 2022
Type: article
Abstract: The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have been unsuccessful because of the poor immunogenicity of Env N-glycans. Here, we report cross-reactivity of glycan-binding bnAbs with self- and non-self N-glycans and glycoprotein antigens from different life-stages of Schistosoma mansoni. Using the IAVI Protocol C HIV infection cohort, we examine the relationship between S. mansoni seropositivity and development of bnAbs targeting glycan-dependent epitopes. We show that the unmutated common ancestor of the N332/V3-specific bnAb lineage PCDN76, isolated from an HIV-infected donor with S. mansoni seropositivity, binds to S. mansoni cercariae while lacking reactivity to gp120. Overall, these results present a strategy for elicitation of glycan-reactive bnAbs which could be exploited in HIV-1 vaccine development.
Source: Cell Reports
Authors: Isabella Huettner, Stefanie A. Krumm, Sonia Serna, Katarzyna Brzezicka, Serena Monaco, Samuel Walpole, Angela van Diepen, Fiona Allan, Thomas Hicks, Simon Kimuda, Aidan M. Emery, Susan Allen, William Kilembe, Shabir Lakhi, Mubiana Inambao, Etienne Karita, Anatoli Kamali, Eduard J. Sanders, Omu Anzala, Vinodh Edward, Linda-Gail Bekker, Jianming Tang, Jill Gilmour, Eric Hunter, Matt Price, Elise Landais, Cornelis H. Hokke, Jesus Angulo, Niels Reichardt, Katie J. Doores
Institutions: King's College London, CIC biomaGUNE, University of East Anglia, Norwich Research Park, Leiden University Medical Center, Natural History Museum, International AIDS Vaccine Initiative, Consejo Superior de Investigaciones Científicas, Instituto de Investigaciones Químicas, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Centro de Investigación Biomédica en Red
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: United States Agency for International Development, Bill and Melinda Gates Foundation, International AIDS Vaccine Initiative, World Bank Group, Irish Aid, Wellcome Trust, Ministerio de Ciencia, Innovación y Universidades, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, National Institute for Health and Care Research, Department for International Development, UK Government, King's College London, European Commission, Rosetrees Trust, Department for International Development, Haridus- ja Teadusministeerium, Udenrigsministeriet, Ministry of Finance Japan, Ministerie van Buitenlandse Zaken, Directorate for Biological Sciences, Direktoratet for Utviklingssamarbeid, HORIZON EUROPE Framework Programme, Medical Research Council, Biotechnology and Biological Sciences Research Council, Agencia Estatal de Investigación, NIHR Exeter Clinical Research Facility, National Institute of Allergy and Infectious Diseases
Awards: G1070506449, SCAN: The Schistosomiasis Collections at the Natural History Museum., G1289431254, G1710272781, G1730981309, G2261121936, Towards understanding the glycan code: next generation structural glycobiology for accurate description of protein-glycan complexes, G2803059671, G3528081209, G3898537969, G3942317427, The Norwich Research Park Biosciences Doctoral Training Partnership, G493002548, SCAN: The Schistosomiasis Collections at the Natural History Museum., G5137951535, Dissecting the host immune response to bacterial and HIV carbohydrate antigens to guide vaccine design, G5555131222, European AIDS Vaccine Initiative 2020, G6805808473, G6816589665, G6966558150, G7100189696, G7686276234, G7870327463, G8100516313, G8293798641, G8684520763
OpenAlex ID: W4220705358