Vaccination induces HIV broadly neutralizing antibody precursors in humans-Reference-Cited by-同舟云学术

Vaccination induces HIV broadly neutralizing antibody precursors in humans

Published:2022-12-02 Issue:6623 Volume:378 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Leggat David J.¹^ORCID,Cohen Kristen W.²^ORCID,Willis Jordan R.³⁴⁵^ORCID,Fulp William J.²,deCamp Allan C.²^ORCID,Kalyuzhniy Oleksandr³⁴⁵^ORCID,Cottrell Christopher A.³⁴⁵^ORCID,Menis Sergey³⁴⁵,Finak Greg²^ORCID,Ballweber-Fleming Lamar²^ORCID,Srikanth Abhinaya¹,Plyler Jason R.¹,Schiffner Torben³⁴⁵^ORCID,Liguori Alessia³⁴⁵^ORCID,Rahaman Farhad⁶^ORCID,Lombardo Angela⁶^ORCID,Philiponis Vincent⁶,Whaley Rachael E.²^ORCID,Seese Aaron²^ORCID,Brand Joshua¹^ORCID,Ruppel Alexis M.¹,Hoyland Wesley¹^ORCID,Yates Nicole L.⁷^ORCID,Williams LaTonya D.⁷^ORCID,Greene Kelli⁸,Gao Hongmei⁸^ORCID,Mahoney Celia R.²,Corcoran Martin M.⁹,Cagigi Alberto¹^ORCID,Taylor Alison¹^ORCID,Brown David M.¹⁰^ORCID,Ambrozak David R.¹,Sincomb Troy³⁴⁵^ORCID,Hu Xiaozhen³⁴⁵^ORCID,Tingle Ryan³⁴⁵^ORCID,Georgeson Erik³⁴⁵^ORCID,Eskandarzadeh Saman³⁴⁵^ORCID,Alavi Nushin³⁴⁵^ORCID,Lu Danny³⁴⁵^ORCID,Mullen Tina-Marie³⁴⁵^ORCID,Kubitz Michael³⁴⁵,Groschel Bettina³⁴⁵^ORCID,Maenza Janine²¹¹^ORCID,Kolokythas Orpheus¹²^ORCID,Khati Nadia¹³,Bethony Jeffrey¹⁴,Crotty Shane⁴¹⁵¹⁶^ORCID,Roederer Mario¹^ORCID,Karlsson Hedestam Gunilla B.⁹¹¹^ORCID,Tomaras Georgia D.⁷^ORCID,Montefiori David⁸^ORCID,Diemert David¹⁴¹⁷^ORCID,Koup Richard A.¹^ORCID,Laufer Dagna S.⁶,McElrath M. Juliana²¹¹^ORCID,McDermott Adrian B.¹^ORCID,Schief William R.³⁴⁵¹⁸^ORCID

Affiliation:

1. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

2. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

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

4. Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.

5. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

6. IAVI, New York, NY 10004, USA.

7. Center for Human Systems Immunology, Departments of Surgery, Immunology, Molecular Genetics and Microbiology, Duke University, Durham, NC 27701, USA.

8. Duke University Medical Center, Durham, NC 27701, USA.

9. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

10. The Foundation for the National Institutes of Health, North Bethesda, MD 20852, USA.

11. Department of Medicine, University of Washington, Seattle, WA 98195, USA.

12. Department of Radiology, University of Washington, Seattle, WA 98195, USA.

13. Department of Radiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.

14. Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA.

15. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

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

17. Department of Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.

18. The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.

Abstract

Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine–priming candidate eOD-GT8 60mer adjuvanted with AS01Bhad a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference116 articles.

1. An HIV Vaccine Is Essential for Ending the HIV/AIDS Pandemic

2. A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge

3. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition

4. Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition

5. Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies

Cited by 64 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Prophylactic HIV-1 vaccine trials: past, present, and future;The Lancet HIV;2024-02

2. Recent progress in mRNA cancer vaccines;Human Vaccines & Immunotherapeutics;2024-01-28

3. Diverse competitor B cell responses to a germline-targeting priming immunogen in human Ig loci transgenic mice;2024-01-23

4. Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques;Cell;2024-01

5. Targeting HIV persistence in the tissue;Current Opinion in HIV and AIDS;2023-12-14