Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines

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 exos...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2021-11, Vol.207 (10), p.2405-2410
Main Authors: Bansal, Sandhya, Perincheri, Sudhir, Fleming, Timothy, Poulson, Christin, Tiffany, Brian, Bremner, Ross M, Mohanakumar, Thalachallour
Format: Article
Language:English
Subjects:
Animals
Antibodies, Viral - metabolism
Blood Circulation
BNT162 Vaccine
Cells, Cultured
COVID-19 - immunology
COVID-19 Vaccines - immunology
Exosomes - immunology
Exosomes - metabolism
Healthy Volunteers
Humans
Immunization
Interferon-gamma - metabolism
Mice
Mice, Inbred C57BL
SARS-CoV-2 - physiology
Spike Glycoprotein, Coronavirus - immunology
Spike Glycoprotein, Coronavirus - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Tumor Necrosis Factor-alpha - metabolism
Vaccination
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.2100637