Germline-targeting chimpanzee SIV Envelopes induce V2-apex broadly neutralizing-like B cell precursors in a rhesus macaque infection model
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Abstract
Eliciting broadly neutralizing antibodies-(bnAbs) remains a major goal of HIV-1 vaccine research. Previously, we showed that a soluble chimpanzee SIV Envelope-(Env) trimer, MT145K, bound several human V2-apex bnAb-precursors and stimulated an appropriate response in V2-apex bnAb precursor-expressing knock-in mice. Here, we tested the immunogenicity of three MT145 variants (MT145, MT145K, MT145K.dV5) expressed as chimeric simian-chimpanzee-immunodeficiency-viruses-(SCIVs) in rhesus macaques-(RMs). All three viruses established productive infections with high setpoint vRNA titers. RMs infected with the germline-targeting SCIV_MT145K and SCIV_MT145K.dV5 exhibited larger and more clonally expanded B cell lineages featuring long anionic heavy chain complementary-determining-regions-(HCDR3s) compared with wildtype SCIV_MT145. Moreover, antigen-specific B cell analysis revealed enrichment for long-CDHR3-bearing antibodies in SCIV_MT145K.dV5 infected animals with paratope features resembling prototypic V2-apex bnAbs and their precursors. Although none of the animals developed bnAbs, these results show that germline-targeting SCIVs can activate and preferentially expand B cells expressing V2-apex bnAb-like precursors, the first step in bnAb elicitation.
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Article activity feed
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Suvadip Mallick, Ryan Krause
Review 3: "Germline-targeting Chimpanzee SIV Envelopes Induce V2-apex Broadly Neutralizing-like B Cell Precursors in a Rhesus Macaque Infection Model"
Reviewers deemed the preprint potentially informative pending revisions addressing limitations around conclusively demonstrating V2-apex specificity and relating antibody features to properties.
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Cynthia Derdeyn
Review 1: "Germline-targeting Chimpanzee SIV Envelopes Induce V2-apex Broadly Neutralizing-like B Cell Precursors in a Rhesus Macaque Infection Model"
Reviewers deemed the preprint potentially informative pending revisions addressing limitations around conclusively demonstrating V2-apex specificity and relating antibody features to properties.
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Anonymous
Review 2: "Germline-targeting Chimpanzee SIV Envelopes Induce V2-apex Broadly Neutralizing-like B Cell Precursors in a Rhesus Macaque Infection Model"
Reviewers deemed the preprint potentially informative pending revisions addressing limitations around conclusively demonstrating V2-apex specificity and relating antibody features to properties.
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Strength of evidence
Reviewers: C Derdeyn (University of Washington) | 📗📗📗📗◻️
Anonymous | 📒📒📒 ◻️◻️
S Mallick & R Krause (University of Pennsylvania) | 📒📒📒◻️◻️ -