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TitleVaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques.
Journal, issue, pagesCell, Vol. 187, Issue 1, Page 79-94.e24, Year 2024
Publish dateJan 4, 2024
AuthorsKevin O Saunders / James Counts / Bhishem Thakur / Victoria Stalls / Robert Edwards / Kartik Manne / Xiaozhi Lu / Katayoun Mansouri / Yue Chen / Rob Parks / Maggie Barr / Laura Sutherland / Joena Bal / Nicholas Havill / Haiyan Chen / Emily Machiele / Nolan Jamieson / Bhavna Hora / Megan Kopp / Katarzyna Janowska / Kara Anasti / Chuancang Jiang / Elizabeth Van Itallie / Sravani Venkatayogi / Amanda Eaton / Rory Henderson / Christopher Barbosa / S Munir Alam / Sampa Santra / Drew Weissman / M Anthony Moody / Derek W Cain / Ying K Tam / Mark Lewis / Wilton B Williams / Kevin Wiehe / David C Montefiori / Priyamvada Acharya / Barton F Haynes /
PubMed AbstractThe CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs ...The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glycans, expansion of appropriate naive B cells with immunogens, and selection of functional antibody mutations. Here, we demonstrate that immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAb bound to HIV-1 Env demonstrated binding angles and heavy-chain interactions characteristic of all known human CD4-mimicking bnAbs. Macaque nAb were derived from variable and joining gene segments orthologous to the genes of human VH1-46-class bnAb. This vaccine study initiated in primates the B cells from which CD4bs bnAbs can derive, accomplishing the key first step in the development of an effective HIV-1 vaccine.
External linksCell / PubMed:38181743 / PubMed Central
MethodsEM (single particle)
Resolution4.25 - 6.78 Å
Structure data

41810

8u1d

EMDB-41810, PDB-8u1d:
Cryo-EM structure of vaccine-elicited CD4 binding site antibody DH1285 bound to HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env Local Refinement
Method: EM (single particle) / Resolution: 4.25 Å

EMDB-41820: Cryo-EM structure of vaccine-elicited CD4 binding site antibody DH1285 bound to HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-41823: Cryo-EM structure of vaccine-elicited CD4 binding site antibody DH1285 bound to HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env
Method: EM (single particle) / Resolution: 5.42 Å

EMDB-41838: Cryo-EM structure of vaccine-elicited CD4 binding site antibody DH1285 bound to partially open HIV-1 CH505TFchim.6R.SOSIP.664v4.1 Env
Method: EM (single particle) / Resolution: 6.78 Å

Chemicals

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

Source
  • human immunodeficiency virus 1
  • macaca mulatta (Rhesus monkey)
KeywordsVIRAL PROTEIN / HIV-1 Vaccine induced neutralizing antibody / CD4 binding site antibody / gp120 / DH1285 / IgG / rhesus macaques / CH505M5chimer.6R.SOSIP.664v4.1 Env

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