Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates-Reference-Cited by-同舟云学术

Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates

Published:2024-05-17 Issue:6697 Volume:384 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Steichen Jon M.¹²³^ORCID,Phung Ivy³⁴⁵^ORCID,Salcedo Eugenia¹²³^ORCID,Ozorowski Gabriel²³⁶^ORCID,Willis Jordan R.¹²³^ORCID,Baboo Sabyasachi³⁷^ORCID,Liguori Alessia¹²³^ORCID,Cottrell Christopher A.¹²³^ORCID,Torres Jonathan L.²³⁶^ORCID,Madden Patrick J.³⁴^ORCID,Ma Krystal M.¹²³^ORCID,Sutton Henry J.³⁴^ORCID,Lee Jeong Hyun¹²³^ORCID,Kalyuzhniy Oleksandr¹²³^ORCID,Allen Joel D.³⁸^ORCID,Rodriguez Oscar L.⁹,Adachi Yumiko¹²³^ORCID,Mullen Tina-Marie¹²³^ORCID,Georgeson Erik¹²³^ORCID,Kubitz Michael¹²³,Burns Alison¹²³^ORCID,Barman Shawn¹²³^ORCID,Mopuri Rohini¹⁰¹¹^ORCID,Metz Amanda¹⁰¹¹^ORCID,Altheide Tasha K.³⁴,Diedrich Jolene K.⁷^ORCID,Saha Swati⁹,Shields Kaitlyn⁹,Schultze Steven E.⁹,Smith Melissa L.⁹^ORCID,Schiffner Torben¹²³,Burton Dennis R.¹²³¹²^ORCID,Watson Corey T.⁹^ORCID,Bosinger Steven E.¹⁰¹¹^ORCID,Crispin Max³⁸^ORCID,Yates John R.³⁷^ORCID,Paulson James C.¹³⁷^ORCID,Ward Andrew B.²³⁶^ORCID,Sok Devin¹²³^ORCID,Crotty Shane³⁴⁵^ORCID,Schief William R.¹²³¹²¹³^ORCID

Affiliation:

1. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

2. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.

3. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.

4. Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

5. Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.

6. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

7. Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.

8. School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.

9. Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40202, USA.

10. Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30322, USA.

11. Department of Pathology and Laboratory Medicine, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.

12. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

13. Moderna, Inc., Cambridge, MA 02139, USA.

Abstract

Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo–electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adj8321

Reference66 articles.

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