Germline-targeting HIV vaccination induces neutralizing antibodies to the CD4 binding site-Reference-Cited by-同舟云学术

Germline-targeting HIV vaccination induces neutralizing antibodies to the CD4 binding site

Published:2024-08-30 Issue:98 Volume:9 Page:
ISSN:2470-9468
Container-title:Science Immunology
language:en
Short-container-title:Sci. Immunol.

Author:

Caniels Tom G.¹²^ORCID,Medina-Ramìrez Max¹²^ORCID,Zhang Shiyu³^ORCID,Kratochvil Sven⁴^ORCID,Xian Yuejiao³,Koo Ja-Hyun⁴^ORCID,Derking Ronald¹²,Samsel Jakob⁵⁶^ORCID,van Schooten Jelle¹²^ORCID,Pecetta Simone⁴^ORCID,Lamperti Edward⁴^ORCID,Yuan Meng³^ORCID,Carrasco María Ríos¹²^ORCID,del Moral Sánchez Iván¹²^ORCID,Allen Joel D.⁷^ORCID,Bouhuijs Joey H.¹²^ORCID,Yasmeen Anila⁸^ORCID,Ketas Thomas J.⁸^ORCID,Snitselaar Jonne L.¹²^ORCID,Bijl Tom P. L.¹²,Martin Isabel Cuella¹²^ORCID,Torres Jonathan L.³^ORCID,Cupo Albert⁸^ORCID,Shirreff Lisa⁹^ORCID,Rogers Kenneth⁹^ORCID,Mason Rosemarie D.⁵^ORCID,Roederer Mario⁵^ORCID,Greene Kelli M.¹⁰,Gao Hongmei¹⁰^ORCID,Silva Catarina Mendes¹²^ORCID,Baken Isabel J. L.¹²^ORCID,Tian Ming¹¹^ORCID,Alt Frederick W.¹¹^ORCID,Pulendran Bali¹²^ORCID,Seaman Michael S.¹³^ORCID,Crispin Max⁷^ORCID,van Gils Marit J.¹²^ORCID,Montefiori David C.¹⁰^ORCID,McDermott Adrian B.⁵^ORCID,Villinger François J.⁹^ORCID,Koup Richard A.⁵^ORCID,Moore John P.⁸^ORCID,Klasse Per Johan⁸^ORCID,Ozorowski Gabriel³^ORCID,Batista Facundo D.¹⁴^ORCID,Wilson Ian A.³¹⁵^ORCID,Ward Andrew B.³^ORCID,Sanders Rogier W.¹²⁸^ORCID

Affiliation:

1. Amsterdam UMC, location AMC, University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.

2. Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, Netherlands.

3. Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA.

4. Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA.

5. Vaccine Research Center (VRC), NIAID, NIH, Bethesda, MD, USA.

6. Institute for Biomedical Sciences, George Washington University, Washington, DC, USA.

7. School of Biological Sciences, University of Southampton, Southampton, UK.

8. Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.

9. New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.

10. Duke University Medical Center, Durham, NC, USA.

11. Howard Hughes Medical Institute, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA.

12. Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.

13. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.

14. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.

15. Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, CA, USA.

Abstract

Eliciting potent and broadly neutralizing antibodies (bnAbs) is a major goal in HIV-1 vaccine development. Here, we describe how germline-targeting immunogen BG505 SOSIP germline trimer 1.1 (GT1.1), generated through structure-based design, engages a diverse range of VRC01-class bnAb precursors. A single immunization with GT1.1 expands CD4 binding site (CD4bs)–specific VRC01-class B cells in knock-in mice and drives VRC01-class maturation. In nonhuman primates (NHPs), GT1.1 primes CD4bs-specific neutralizing serum responses. Selected monoclonal antibodies (mAbs) isolated from GT1.1-immunized NHPs neutralize fully glycosylated BG505 virus. Two mAbs, 12C11 and 21N13, neutralize subsets of diverse heterologous neutralization-resistant viruses. High-resolution structures revealed that 21N13 targets the same conserved residues in the CD4bs as VRC01-class and CH235-class bnAbs despite its low sequence similarity (~40%), whereas mAb 12C11 binds predominantly through its heavy chain complementarity-determining region 3. These preclinical data underpin the ongoing evaluation of GT1.1 in a phase 1 clinical trial in healthy volunteers.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciimmunol.adk9550

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