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

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.

SUBMITTER: Huettner I

PROVIDER: S-EPMC10073069 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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

Huettner Isabella I Krumm Stefanie A SA Serna Sonia S Brzezicka Katarzyna K Monaco Serena S Walpole Samuel S van Diepen Angela A Allan Fiona F Hicks Thomas T Kimuda Simon S Emery Aidan M AM Landais Elise E Hokke Cornelis H CH Angulo Jesus J Reichardt Niels N Doores Katie J KJ

Cell reports 20220301 13

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-sel ...[more]

PMID: 35354052

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Project description:IntroductionA primary focus of HIV-1 vaccine development is the activation of B cell receptors for naïve or precursor broadly neutralizing antibodies (bnAbs), followed by expansion and maturation of bnAb B cell lineage intermediates leading to highly affinity-matured bnAbs. HIV-1 envelope (Env) encodes epitopes for bnAbs of different specificities. Design of immunogens to induce bnAb precursors of different specificities and mature them into bnAb status is a goal for HIV-1 vaccine development. We review vaccine strategies for bnAb lineages development and highlight the immunological barriers that these strategies must overcome to generate bnAbs.MethodsWe provide perspectives based on published research articles and reviews.DiscussionThe recent Antibody Mediated Protection (AMP) trial that tested the protective efficacy of one HIV-1 Env bnAb specificity demonstrated that relatively high levels of long-lasting serum titers of multiple specificities of bnAbs will be required for protection from HIV-1 transmission. Current vaccine efforts for induction of bnAb lineages are focused on immunogens designed to expand naïve HIV-1 bnAb precursor B cells following the recent success of vaccine-induction of bnAb precursor B cells in macaques and humans. BnAb precursor B cells serve as templates for priming-immunogen design. However, design of boosting immunogens for bnAb maturation requires knowledge of the optimal immunogen design and immunological environment for bnAb B cell lineage affinity maturation. BnAb lineages acquire rare genetic changes as mutations during B cell maturation. Moreover, the immunological environment that supports bnAb development during HIV-1 infection is perturbed with an altered B cell repertoire and dysfunctional immunoregulatory controls, suggesting that in normal settings, bnAb development will be disfavoured. Thus, strategies for vaccine induction of bnAbs must circumvent immunological barriers for bnAb development that normally constrain bnAb B cell affinity maturation.ConclusionsA fully protective HIV-1 vaccine needs to induce durable high titers of bnAbs that can be generated by a sequential set of Env immunogens for expansion and maturation of bnAb B cell lineages in a permitted immunological environment. Moreover, multiple specificities of bnAbs will be required to be sufficiently broad to prevent the escape of HIV-1 strains during transmission.

Dataset Information

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

Publications

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

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