Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination
Open accessAbstract
Significance: We explored the effect of nontraditional vaccine dosing profiles on antibody titers of vaccines and discovered that certain dosing profiles demonstrate >10-fold higher antibody production than the traditional single-dose prime–boost method. We also present a computational model that captures the experimental results and provides a mechanistic understanding of the biology behind the effectiveness of our strategy. This work has clinical significance in vaccine design because it is a simple method to increase the efficacy of subunit vaccines, which may lead to the development of efficacious vaccines for diseases such as HIV.
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Sustained antigen availability during the germinal centre reaction has been shown to increase antibody production by approximately tenfold.
“Sustained antigen availability during the germinal centre reaction has been shown to increase antibody production by approximately tenfold199.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [199]
An mRNA vaccine that achieves high and sustained antigen availability will benefit the magnitude and duration of both T cell and B cell responses.
“Nevertheless, it can be expected that an mRNA vaccine that achieves high and sustained antigen availability, will benefit the magnitude and duration of both T cell and B cell responses [11,[189][190][191].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [11]
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Self-citation
- Authors
- Tam, H. H., Melo, M. B., Kang, M., Pelet, J. M., Ruda, V. M., Foley, M. H., Hu, J. K., Kumari, S., Crampton, J., Baldeon, A. D., Sanders, R. W., Moore, J. P., Crotty, S., Langer, R., Anderson, D. G., Chakraborty, A. K., & Irvine, D. J.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Massachusetts Institute of Technology (US)
- La Jolla Institute for Immunology (US)
- Cornell University (US)
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-10-04
- Volume
- 113
- Issue
- 43
- Pages
- E6639-E6648
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5086995
- OpenAlex
- W2527863850
- Cited by
- 425
- References
- 68
- Citations by year
- 2026: 50 · 2025: 50 · 2024: 61 · 2023: 46 · 2022: 53 · 2021: 61 · 2020: 40 · 2019: 34 · 2018: 19 · 2017: 9 · 2016: 1
- FWCI
- 14.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- HHS | NIH | National Institute of Allergy and Infectious Diseases (UM1AI100663, AI110657)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- HIV vaccine, antibody response, osmotic pump, adjuvants, humoral immunity, T follicular helper cells, germinal center B cells
- MeSH terms
- Immunogenicity, Vaccine, Adjuvants, Immunologic, Animals, Antibodies, Viral, Antibody Affinity, B-Lymphocytes, Cricetulus, Drug Administration Schedule, Female, Humans, Lipid A, Mice, Inbred C57BL, Osmotic Pressure, Recombinant Fusion Proteins, Vaccination, HIV Envelope Protein gp120, Infusion Pumps, Implantable, CHO Cells, AIDS Vaccines, Germinal Center, Mice, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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