Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

Abstract

Objectives Since universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response. Methods Three healthcare workers received 30 μg BNT162b2 mRNA Covid-19 Pfizer Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), anti-S1/S2 and anti-RBD IgG, anti-RBD and anti-N/S1 IgM, and anti-S1 IgA. Results All subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG levels increased between 91 and 368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by ∼30-, ∼8- and ∼8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing ∼50 days after the first vaccine dose. Anti-S1 IgA levels increased between 7 and 11 days after the first dose, slightly declined before the second dose, after which levels augmented by ∼24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4- to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all-time points. Conclusions BNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving anti-SARS-Cov-2 IgG and IgA, magnified by the second vaccine dose.

SARS-CoV-2 mRNA Vaccine Induces Robust Specific and Cross-reactive IgG and Unequal Strain-specific Neutralizing Antibodies in Naïve and Previously Infected Recipients

“…IgA production, by contrast, is induced in more modest quantities, comparable to what is seen in mild disease 11 . Induction of strong IgG and, low IgA levels in naïve patients after receiving one of the two mRNA vaccines has also been recently reported in other independent studies 42 . Serum IgA levels are not a direct measure of secretory IgA levels, since systemic IgA are predominantly made of monomeric IgA1 subclass, and mucosal IgA is a polymeric IgA2 subclass 43 .…”

Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals

“…This suggests that, even though the vaccine alone did not generate an optimal B.1.1.7 neutralization response (compared to natural infection), it was capable of boosting the full cross-neutralization response pre-established by natural infection, in line with other reports [27,28]. Importantly, vaccinated individuals were all sampled at least 7 days after the second dose of vaccine, at a time when both humoral and neutralizing responses have reportedly reached a plateau [29,30]. However, another study suggests that the kinetics of neutralization following vaccination might vary depending on the variant [31].…”

Anti-SARS-CoV-2 Receptor-Binding Domain Total Antibodies Response in Seropositive and Seronegative Healthcare Workers Undergoing COVID-19 mRNA BNT162b2 Vaccination

“…To this end, the identification of subjects with low/modest postvaccine immune response will be vital for limiting the potential unfavorable impact of emerging SARS-CoV-2 variants (especially those bearing the so-called "immune escape mutations"), ensuring adequate personal and community immune protection and limiting viral circulation, thereby reducing the risk that novel and even more dangerous mutations will accumulate [30][31][32]. Moreover, recent evidence of a sustained IgA response after mRNA-LNPs vaccination [33], combined with clinical observations of decreased viral load in the limited number of reported cases after inoculation [34], suggests that these vaccines can reduce viral replication, which itself would result in decreased likelihood of new mutation generation in the case of asymptomatic/symptomatic SARS-CoV-2 infection of a vaccinated individual.…”