Pharmacokinetic tuning of protein–antigen fusions enhances the immunogenicity of T-cell vaccines
Name
nihms-1632353.pdf
Description
Accepted version
Size
1.97 MB
Format
Adobe PDF
Checksum (MD5)
cff827817d9c38ca23da46806710a470
Author(s)
Mehta, Naveen K
Pradhan, Roma V
Soleimany, Ava P
Moynihan, Kelly D
Rothschilds, Adrienne M
Momin, Noor
Rakhra, Kavya
Mata-Fink, Jordi
Bhatia, Sangeeta N
Wittrup, K Dane
Date Issued
2020
Journal
Nature Biomedical Engineering
Publisher
Springer Science and Business Media LLC
Version
Author's final manuscript
Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature Limited. The formulations of peptide-based antitumour vaccines being tested in clinical studies are generally associated with weak potency. Here, we show that pharmacokinetically tuning the responses of peptide vaccines by fusing the peptide epitopes to carrier proteins optimizes vaccine immunogenicity in mice. In particular, we show in immunized mice that the carrier protein transthyretin simultaneously optimizes three factors: efficient antigen uptake in draining lymphatics from the site of injection, protection of antigen payloads from proteolytic degradation and reduction of antigen presentation in uninflamed distal lymphoid organs. Optimizing these factors increases vaccine immunogenicity by up to 90-fold and maximizes the responses to viral antigens, tumour-associated antigens, oncofetal antigens and shared neoantigens. Protein–peptide epitope fusions represent a facile and generalizable strategy for enhancing the T-cell responses elicited by subunit vaccines.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Chemical Engineering
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Materials Science and Engineering
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DOI of Published Version
https://doi.org/10.1038/S41551-020-0563-4
