Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients

Severe acute respiratory syndrome coronavirus 2 proteins were measured in longitudinal plasma samples collected from 13 participants who received two doses of mRNA-1273 vaccine.

mRNA-1273 encodes the severe acute respiratory syndrome coronavirus spike antigen with a transmembrane anchor and S1-S2 cleavage site.

Data have demonstrated the elicitation of binding and neutralization antibodies against the spike protein by the mRNA-1273 vaccine in humans, thereby inferring that spike protein was produced and induced an immune response [2-5]. However, critical data demonstrating the direct production of spike protein via translation from the mRNA-1273 vaccine in these studies are missing, precluding a full understanding of the vaccine mechanism.

Ultrasensitive single-molecule array assays were used for the detection of SARS-CoV-2 antigens spike, S1, and nucleocapsid and antibodies immunoglobulin G, immunoglobulin A, and immunoglobulin M against SARS-CoV-2 spike, S1, receptor binding domain, and nucleocapsid, as previously described [6, 7]. The ultralow detection limits of the Simoa assays enable detection of antigen and antibody production in the early stages postvaccination and quantification of changes in levels over the course of both vaccine injections.

The Simoa antigen assays for spike, S1, and nucleocapsid were previously validated in plasma from pre-pandemic healthy subjects, pre-pandemic patients with respiratory infections, COVID-19 negative patients, and COVID-19 positive patients.

After the first 100-µg dose, the mRNA-1273 vaccine produced detectable levels of S1 antigen in plasma in 11 participants, and spike antigen was detected in 3 of 13 participants.

The inverse correlation between antibody and antigen levels observed is consistent with previous studies investigating SARS-CoV-2 natural infection, in which patients with severe COVID-19 with high plasma antigen levels exhibited antigen clearance upon production of antibodies.

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab465/6279075