Low protease activity in B cell follicles promotes retention of intact antigens after immunization-Reference-Cited by-同舟云学术

Low protease activity in B cell follicles promotes retention of intact antigens after immunization

Published:2023-01-27 Issue:6630 Volume:379 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Aung Aereas¹^ORCID,Cui Ang²³^ORCID,Maiorino Laura¹^ORCID,Amini Ava P.¹³⁴⁵^ORCID,Gregory Justin R.¹,Bukenya Maurice¹^ORCID,Zhang Yiming¹⁶^ORCID,Lee Heya¹,Cottrell Christopher A.⁷⁸^ORCID,Morgan Duncan M.¹⁹^ORCID,Silva Murillo¹^ORCID,Suh Heikyung¹,Kirkpatrick Jesse D.¹³^ORCID,Amlashi Parastoo¹^ORCID,Remba Tanaka¹^ORCID,Froehle Leah M.¹⁰^ORCID,Xiao Shuhao¹^ORCID,Abraham Wuhbet¹,Adams Josetta¹^ORCID,Love J. Christopher¹²⁹¹⁰^ORCID,Huyett Phillip¹¹^ORCID,Kwon Douglas S.¹⁰^ORCID,Hacohen Nir²¹²^ORCID,Schief William R.⁸¹⁰¹³¹⁴^ORCID,Bhatia Sangeeta N.¹²³¹⁵¹⁶^ORCID,Irvine Darrell J.¹⁶⁸¹⁰¹⁷^ORCID

Affiliation:

1. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.

2. Broad Institute of MIT and Harvard, Cambridge, MA, USA.

3. Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, MA, USA.

4. Program in Biophysics, Harvard University, Boston, MA, USA.

5. Microsoft Research New England, Cambridge, MA, USA.

6. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

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

8. Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, USA.

9. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

10. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.

11. Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, MA, USA.

12. Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

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

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

15. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.

16. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.

17. Howard Hughes Medical Institute, Cambridge, MA, USA.

Abstract

The structural integrity of vaccine antigens is critical to the generation of protective antibody responses, but the impact of protease activity on vaccination in vivo is poorly understood. We characterized protease activity in lymph nodes and found that antigens were rapidly degraded in the subcapsular sinus, paracortex, and interfollicular regions, whereas low protease activity and antigen degradation rates were detected in the vicinity of follicular dendritic cells (FDCs). Correlated with these findings, immunization regimens designed to target antigen to FDCs led to germinal centers dominantly targeting intact antigen, whereas traditional immunizations led to much weaker responses that equally targeted the intact immunogen and antigen breakdown products. Thus, spatially compartmentalized antigen proteolysis affects humoral immunity and can be exploited.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.abn8934

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