Correlates of neutralizing/SARS-CoV-2-S1-binding antibody response with adverse effects and immune kinetics in BNT162b2-vaccinated individuals

Abstract

While mRNA vaccines against SARS-CoV-2 are exceedingly effective in preventing symptomatic infection, their immune response features remain to be clarified. In the present prospective study, 225 healthy individuals in Japan, who received two BNT162b2 doses, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions) with various determinants were examined and the potency of sera against variants of concerns was determined. Significant rise in NT50s was seen in sera on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation seen between NT50s and adverse effects. NT50s and SARS-CoV-2-S1-binding-IgG levels on day 28 post-1st dose and pain scores following the 2nd dose were greater in women than in men. The average half-life of NT50s was ~ 68 days, and 23.6% (49 out of 208 individuals) failed to show detectable neutralizing activity on day 150. While sera from elite-responders (NT50s > 1,500: the top 4% among the participants) potently to moderately blocked all variants of concerns examined, some sera with low NT50s failed to block the B.1.351-beta strain. Since BNT162b2-elicited immunity against SARS-CoV-2 is short, an additional vaccine or other protective measures are needed.

Systemic Adverse Effects Induced by the BNT162b2 Vaccine Are Associated with Higher Antibody Titers from 3 to 6 Months after Vaccination

“…Not only high Ab responses against SARS-CoV-2 spike protein but also systemic adverse effects induced by the BNT162b2 vaccine were reported to be more common among participants with preexisting immunity due to COVID-19 infection [ 10 ], suggesting that some systemic adverse effects are induced as a more vigorous response to the SARS-CoV-2 spike protein itself produced by the BNT162b2 vaccine. Previous publications reported that adverse effects induced by the BNT162b2 vaccine had no correlation or only low correlation with Ab titers detected immediately after vaccination [ 5 , 6 , 7 , 8 ]. However, to evaluate the long-term effects of vaccination, research should consider Ab titers several months after vaccination and not only the peak level of Ab titers.…”

“…If the maximum vaccine efficacy, including antibody (Ab) responses, is guaranteed, most people will accept a certain severity of vaccination-related adverse effects [ 2 ]. Although several reports concluded that there is no correlation or only low correlation between adverse effects and the Ab titers detected immediately after vaccination [ 5 , 6 , 7 , 8 ], a correlation is expected between adverse effects and the Ab titers detected several months after vaccination [ 9 ]. Antibody titers alone do not correlate perfectly with protection because the benefits of mRNA vaccines include not only B-cell/humoral responses but also T-cell/cell-mediated immunity.…”

Short-Term Adverse Events and Antibody Response to the BNT162b2 SARS-CoV-2 Vaccine in 4156 Health Care Professionals

“…While molecular proof of incident infections and the risk of developing severe forms of COVID-19 determine the efficacy of vaccines, serum levels of spike-specific IgG mirror the immune response [ 5 ]. Furthermore, short-term adverse events are common following each dose of the BNT162b2 vaccine, as evident from the reports on self-reporting apps [ 6 ] with a proposed impact on the IgG response [ 7 ].…”

Successful use of casirivimab/imdevimab anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19

“…Some reports suggest that the effectiveness of COVID-19 vaccines may be reduced in patients on anti-CD20 mAbs treatment due to diminished humoral immune responsiveness [ 11 , 12 ]. However, this patient's serum neutralizing antibodies remained remarkably high for at least one month after administration of casirivimab/imdevimab, considering the results of a study of the neutralizing antibody titer after COVID-19 mRNA vaccination (BNT162b2) in healthy individuals [ 13 ]. Although it is unclear how long neutralizing antibodies persist, monoclonal antibody therapy with casirivimab/imdevimab may be useful for COVID-19 prophylaxis in patients with humoral immunodeficiency, in whom vaccine efficacy is low.…”