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TitleAn engineered immunogen activates diverse HIV broadly neutralizing antibody precursors and promotes acquisition of improbable mutations.
Journal, issue, pagesSci Transl Med, Vol. 17, Issue 780, Page eadr2218, Year 2025
Publish dateJan 8, 2025
AuthorsOlivia M Swanson / Qianyi E Zhang / Elizabeth Van Itallie / Ming Tian / Alecia R Brown / Caitlin Harris / Anyway Brenda Kapingidza / Brianna Rhodes / Lena M Smith / Sravani Venkatayogi / Kenneth Cronin / McKenzie Frazier / Rob Parks / Maggie Bar / Chuancang Jiang / Joshua S Martin Beem / Hwei-Ling Cheng / Jillian Davis / Kelly McGovern / Amanda Newman / Robert J Edwards / Derek Cain / S Munir Alam / Kevin Wiehe / Kevin O Saunders / Priyamvada Acharya / Fred Alt / Barton F Haynes / Mihai L Azoitei /
PubMed AbstractElicitation of HIV broadly neutralizing antibodies (bnAbs) by vaccination first requires the activation of diverse precursors, followed by successive boosts that guide these responses to enhanced ...Elicitation of HIV broadly neutralizing antibodies (bnAbs) by vaccination first requires the activation of diverse precursors, followed by successive boosts that guide these responses to enhanced breadth through the acquisition of somatic mutations. Because HIV bnAbs contain mutations in their B cell receptors (BCRs) that are rarely generated during conventional B cell maturation, HIV vaccine immunogens must robustly engage and expand B cells with BCRs that contain these improbable mutations. Here, we engineered an immunogen that activates diverse precursors of an HIV V3-glycan bnAb and promotes their acquisition of a functionally critical improbable mutation. This immunogen was validated biochemically, structurally, and in three different humanized immunoglobulin mouse models that were designed to test HIV immunogens. These results provide a blueprint for rationally designing priming immunogens that explicitly target the elicitation of antibodies with functional yet improbable mutations.
External linksSci Transl Med / PubMed:39772772
MethodsEM (single particle)
Resolution3.6 - 3.8 Å
Structure data

43879

9aug

EMDB-43879, PDB-9aug:
Cryo-EM structure of CH848.d949.10.17.GS-DH270.UCA3.G57R
Method: EM (single particle) / Resolution: 3.8 Å

43880

9auh

EMDB-43880, PDB-9auh:
Cryo-EM structure of CH848.d949.10.17.GS-DH270.UCA3
Method: EM (single particle) / Resolution: 3.6 Å

43881

9aui

EMDB-43881, PDB-9aui:
Cryo-EM structure of CH848.d949.10.17.GS-DH270.UCA4
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Envelope / Glycoprotein / Trimer / Antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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