Key Points
BNT162b2 induces release of exosomes carrying SARS-CoV-2 spike protein.
Abs to SARS-CoV-2 develop after detection of circulatory exosomes.
Exosomes with SARS-CoV-2 spike protein are immunogenic in mice.
Abstract
Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) causes severe acute respiratory syndrome. mRNA vaccines directed at the SARS-CoV-2 spike protein resulted in development of Abs and protective immunity. To determine the mechanism, we analyzed the kinetics of induction of circulating exosomes with SARS-CoV-2 spike protein and Ab following vaccination of healthy individuals. Results demonstrated induction of circulating exosomes expressing spike protein on day 14 after vaccination followed by Abs 14 d after the second dose. Exosomes with spike protein, Abs to SARS-CoV-2 spike, and T cells secreting IFN-γ and TNF-α increased following the booster dose. Transmission electron microscopy of exosomes also demonstrated spike protein Ags on their surface. Exosomes with spike protein and Abs decreased in parallel after four months. These results demonstrate an important role of circulating exosomes with spike protein for effective immunization following mRNA-based vaccination. This is further documented by induction of humoral and cellular immune responses in mice immunized with exosomes carrying spike protein.
Footnotes
All authors have reviewed and approved the manuscript and have contributed in a substantial and intellectual manner to the work.
This work was supported by National Institutes of Health Grant AI123034 and funds from the St. Joseph foundation (to T.M.).
The online version of this article contains supplemental material.
- Received July 1, 2021.
- Accepted September 15, 2021.
- Copyright © 2021 by The American Association of Immunologists, Inc.
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