Exosomes with COVID spike protein are induced by BNT162b2 (Pfizer–BioNTech) vaccination prior to development of antibodies

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, researchers at St. Joseph’s Hospital and Medical Center 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.

Representative images for exosomes

(A) Representative NanoSight image for exosomes from vaccinated individuals with mean and median sizes (black thin line in the graph indicates the three measurements of the same sample, and red line is the average of all three lines). (B) Transmission electron microscopy images of SARS-CoV-2 spike Ag on exosomes from control exosomes from control and vaccinated individuals. Arrows indicate SARS-CoV-2 spike-positive exosomes. Right side, third image is the zoomed image of positive exosome from vaccinated sample (original magnification x 50,000). We have used anti-coronavirus FIPV3-70 Ab as negative control for both the samples.

Bansal S, Perincheri S, Fleming T, Poulson C, Tiffany B, Bremner RM, Mohanakumar T. (2022) 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. J Immunol 207(10):2405-2410. [article]

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