Differing kinetics of anti-spike protein IgGs and neutralizing antibodies against SARS-CoV-2 after Comirnaty (BNT162b2) immunization.

AIMS: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has had a serious worldwide impact on human health. On December 2020, an immunization campaign with a COVID-19 mRNA vaccine (Comirnaty-BNT162b2 Pfizer-BioNTech) was started in Italy, first targeting healthcare workers (HCWs). This study aims to investigate the antibodies that are response against SARS-CoV-2 vaccine. METHODS AND RESULTS: The kinetics and the persistence of both anti-S1/S2 IgGs and neutralizing antibodies (Nt-Abs) were investigated in 76 HCWs through a 4-month follow-up with multiple testing points starting at the first dose. Temporal analysis of SARS-CoV-2 Abs titre kinetics showed three different stages, with an initial slow growth in the anti-S1/S2 IgGs and Nt-Abs titres, corresponding to the first 4 weeks after the first dose of vaccine, followed by a second stage with peaks in titres, around 35 days after the first dose, and by a third stage (38 to 90-120 days after the first dose) showing a steady decrease in anti-S1/S2 IgGs while Nt-Abs are maintained at stable levels. Moreover, the levels of specific Nt-Abs to SARS-CoV-2 Spike protein are correlated to the anti-S1/S2 IgG titre (R-squared = 0.47; p < 0.001). CONCLUSIONS: The levels of specific Nt-Abs to SARS-CoV-2 Spike protein are correlated to the anti-S1/S2 IgG titre, although Nt-Abs could maintain a more stable titre over the time despite declining IgG Abs titre. SIGNIFICANCE AND IMPACT: This study highlights the kinetics and the persistence of Nt-Abs in HCWs vaccinated with Comirnaty (BNT162b2) Pfizer-BioNTech, and compared the Nt-Abs levels with anti-SARS-CoV-2 S1/S2 IgGs titres during a 4-month follow-up starting at the first dose of vaccine.

Age and Cytokine Gene Variants Modulate the Immunogenicity and Protective Effect of SARS-CoV-2 mRNA-Based Vaccination.

The introduction of anti-SARS-CoV-2 vaccines in late 2020 substantially changed the pandemic picture, inducing effective protection in the population. However, individual variability was observed with different levels of cellular response and neutralizing antibodies. We report data on the impact of age, gender, and 16 single nucleotide polymorphisms (SNPs) of cytokine genes on the anti-SARS-CoV-2 IgG titers measured 31 and 105 days after administration of the second dose of BNT162b2 vaccine to 122 healthy subjects from the health care staff of the Palermo University Hospital, Italy. The higher titers at 31 days were measured in the younger subjects and in subjects bearing T-positive genotypes of IL-1R1 rs2234650 or the GG homozygous genotype of IL-6 rs1800795 SNP. T-positive genotypes are also significantly more common in subjects with higher titers at day 105. In addition, in this group of subjects, the frequency of the CT genotype of IL-4 rs2243250 is higher among those vaccinated with higher titers. Moreover, these SNPs and TNFA rs1800629 are differently distributed in a group of subjects that were found infected by SARS-CoV-2 at day 105 of evaluation. Finally, subjects that were found to be infected by SARS-CoV-2 at day 105 were significantly older than the uninfected subjects. Taken together, these data seem to suggest that age and polymorphisms of key cytokines, which regulate inflammation and humoral immune response, might influence the magnitude of the antibody response to vaccination with BNT162B2, prompting speculation about the possible benefit of a genetic background-based assessment of a personalized approach to the anti-COVID vaccination schedule.

Neutralizing Antibodies Response against SARS-CoV-2 Variants of Concern Elicited by Prior Infection or mRNA BNT162b2 Vaccination.

In order to determine the humoral protective response against SARS-CoV-2, the vaccine-induced and naturally induced neutralizing antibodies (NtAbs) responses against SARS-CoV-2 variants circulating in Italy through in vitro live virus neutralization assay were evaluated. A total of 39 SARS-CoV-2 recovered subjects (COVID-19+) and 63 subjects with a two-dose cycle of the BNT16262 vaccine were enrolled. A single serum sample was tested for COVID-19+ at 35-52 days post-positive swab, while vaccinees blood samples were taken at one (V1) and at three months (V3) after administration of the second vaccine dose. Significantly higher NtAb titers were found against B.1 and Alpha in both COVID-19+ and vaccinees, while lower NtAb titers were detected against Delta, Gamma, and Omicron variants. A comparison between groups showed that NtAb titers were significantly higher in both V1 and V3 than in COVID-19+, except against the Omicron variant where no significant difference was found. COVID-19+ showed lower neutralizing titers against all viral variants when compared to the vaccinees. Two-dose vaccination induced a sustained antibody response against each analyzed variant, except for Omicron. The evolution process of SARS-CoV-2, through variants originating from an accumulation of mutations, can erode the neutralizing effectiveness of natural and vaccine-elicited immunity. Therefore, a need for new vaccines should be evaluated to contain the ongoing pandemic.