Low protease activity in B cell follicles promotes retention of intact antigens after immunization
Year: 2023
Type: article
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.
Source: Science
Authors: Aereas Aung, Ang Cui, Laura Maiorino, Ava P. Amini, Justin R. Gregory, Maurice Bukenya, Yiming Zhang, Heya Lee, Christopher A. Cottrell, Duncan M. Morgan, Murillo Silva, Heikyung Suh, Jesse D. Kirkpatrick, Parastoo Amlashi, Tanaka Remba, Leah M. Froehle, Shuhao Xiao, Wuhbet Abraham, Josetta Adams, J. Christopher Love, Phillip Huyett, Douglas S. Kwon, Nir Hacohen, William R. Schief, Sangeeta N. Bhatia, Darrell J. Irvine
Institutions: Koch Institute for Integrative Cancer Research At MIT, Broad Institute, Harvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Harvard University, Microsoft Research New England (United States), Scripps Research Institute, Ragon Institute of MGH, MIT and Harvard, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Brigham and Women's Hospital, Howard Hughes Medical Institute, Wyss Institute for Biologically Inspired Engineering
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Bill and Melinda Gates Foundation, International AIDS Vaccine Initiative, Ragon Institute of MGH, MIT and Harvard, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Thailand Science Research and Innovation, National Institutes of Health, Ludwig Center for Molecular Oncology, Ludwig Center at Harvard, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences
Awards: Postdoctoral Training Program in AIDS-related Research, G2034479465, International AIDS Vaccine Initiative - to demonstrate that an HIV ENV based immunogen(s) can be designed to elicit bnAbs in humans and has the potential to prevent HIV infection., G2360436881, International AIDS Vaccine Initiative - to develop and test vaccination strategies that are practical, deployable and have the potential to reduce HIV incidence, MIT Center for Environmental Health Sciences, G4103933137, G5735053113, Defense-in-depth against mucosal HIV clade C invasion, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, G9000071565, Cancer Center Support (Core) Grant, Consortium for HIV/AIDS Vaccine Development
OpenAlex ID: W4318141600