Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans

Huettner, Isabella, Krumm, Stefanie A., Serna, Sonia, Brzezicka, Katarzyna, Monaco, Serena, Walpole, Samuel, Van Diepen, Angela, Allan, Fiona, Hicks, Thomas, Kimuda, Simon, Emery, Aidan M., , The IAVI Protocol C Investigators & The IAVI African HIV Researc, Allen, Susan, Kilembe, William, Lakhi, Shabir, Inambao, Mubiana, Karita, Etienne, Kamali, Anatoli, Sanders, Eduard J., Anzala, Omu, Edward, Vinodh, Bekker, Linda-Gail, Tang, Jianming, Gilmour, Jill, Hunter, Eric, Price, Matt, Landais, Elise, Hokke, Cornelis H., Angulo, Jesus, Reichardt, Niels and Doores, Katie J. (2022) Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans. Cell Reports, 38 (13). ISSN 2211-1247

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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.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science > School of Chemistry
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 30 Mar 2022 10:35
Last Modified: 18 Apr 2022 19:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/84349
DOI: 10.1016/j.celrep.2022.110611

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