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

Cell Rep. 2022 Mar 29;38(13):110611. doi: 10.1016/j.celrep.2022.110611.

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.

Keywords: CP: Immunology; HIV-1; Schisotosoma mansoni; glycan epitope; neutralizing antibody; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • HIV Antibodies
  • HIV Infections*
  • HIV-1*
  • Humans
  • Parasites* / metabolism
  • Polysaccharides / metabolism

Substances

  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • HIV Antibodies
  • Polysaccharides