The temporal course of T- and B-cell responses to vaccination with BNT162b2 and mRNA-1273

Abstract

Objectives To investigate the immune systems’ response (and its influencing factors) to vaccination with BNT162b2 or mRNA-1273. Methods 531 vaccinees, recruited from health care professionals, donated samples before, in between, and after the administration of the two doses of the vaccine. T- and B-cell responses were examined via Interferon-γ-release assay as well as detection of antibodies against different epitopes of SARS-CoV-2 (S1 and NCP) via ELISA and binding surrogate neutralization assay. Results were correlated with influence factors such as age, sex, prior infection, vaccine received (BNT162b2 or mRNA-1273), and immunosuppression. Furthermore, antinuclear antibodies (ANA) were measured to screen for autoimmune responses following the vaccination with an mRNA vaccine. Results No markers of immunity against SARS-CoV-2 were found before the first vaccination. Two weeks after it, specific responses against SARS-CoV-2 were already measurable (median±median absolute deviation (MAD): anti-S1 IgG: 195.5±172.7 BAU/ml; IgA: 6.7±4.9 OD; surrogate neutralization: 39±23.7 %), which were significantly increased two weeks after the second dose (anti-S1 IgG: 3744±2571.4 BAU/ml; IgA: 12±0 OD; surrogate neutralization: 100±0 %, IFN-γ: 1897.2±886.7 mIU/ml). Responses were stronger for younger participants (this difference decreasing after the second dose). Further influences were previous infection with SARS-CoV-2 (causing significantly stronger responses after the first dose compared to unexposed individuals (p ≤ 0.0001)) and the vaccine received (significantly stronger reactions for recipients of mRNA-1273 after both doses (p < 0.05 – 0.0001)). Some forms of immunosuppression significantly impeded the immune response to the vaccination (with no observable immune response in three immunosuppressed participants). There was no significant induction of ANA by the vaccination (no change in qualitative ANA results (p = 0.2592), nor ANA titers (p = 0.08) from pre to post vaccination. Conclusions Both vaccines elicit strong and specific immune responses against SARS-CoV-2, which become detectable one week (T-cell-response) or two weeks (B-cell-response) after the first dose.

Kinetics of the Antibody Response to Boostering With Three Different Vaccines Against SARS-CoV-2

“…Whether or not the observed differences between both mRNA-based vaccines are clinically relevant remains debatable. There are some surprising findings in the data: While we found in an earlier study that anti-S1 IgA responses after a first dose of an mRNA based vaccine precedes the anti-S1 IgG response (22), we could not find any difference in latency between the IgG and the IgA response in the current study. A possible explanation is the recent finding that a first dose of BNT162b2 induces an IgA-dominant plasmablast response (mainly against the S2 epitope), which might represent a recall response of mucosal memory B-cells formed in response to previous pulmonary coronavirus infections, whereas the (neutralizing) anti-S1 response (IgA and IgG) most likely stems from naïve B-cells which are recruited after the first dose and boostered after the second (23).…”

“…Our study has several limitations: Due to considerations of practicability, we did not examine any part of the T-cell response after the second vaccination. Data we gathered for the first dose of the vaccine suggest that the T-cell response might be detectable even earlier after the second dose than the examined antibody response ( 22 ). We did not perform a neutralization assay in the proper sense, but rather a surrogate neutralization assay.…”

Trajectory of IgG to SARS-CoV-2 After Vaccination With BNT162b2 or mRNA-1273 in an Employee Cohort and Comparison With Natural Infection

“…The current findings indicate that BNT162b2 and mRNA-1273 both achieve similar peak IgG levels to the SARS-CoV-2 spike RBD antigen following two vaccine doses. Although this finding is at odds with some earlier reports ( 11 , 20 , 21 ), including an interim analysis of the current cohort ( 12 ), it is at least partially explained by different rates of antibody decay that occur following immunization with BNT162b2 and mRNA-1273 and is supported by a recent report from Montoya et al ( 22 ). The detailed kinetic analysis here reveals that IgG levels in recipients of BNT162b2 are dropping markedly (eg, 40%), and to a greater extent than mRNA-1273, as soon as 21 days after the booster immunization.…”

SARS-CoV-2 antibody response eight months after vaccination with mRNA vaccines. Influence of prior SARS-CoV-2 exposure

“…As might be expected, previous infection was the main factor related with increased immunogenicity against the virus [7] and with the persistence of the level of antibodies in vaccinated patients [ 8 ]. On the other hand, in our cohort, as in previous studies [ 9 , 10 ], vaccination with mRNA-1273 elicited somewhat stronger immune responses than BNT162b2. The longer interval between doses and the higher mRNA doses of the mRNA-1273 vaccine are proposed as likely explanations.…”