BNT162b2 mRNA SARS-CoV-2 Vaccine Elicits High Avidity and Neutralizing Antibodies in Healthcare Workers

Abstract

The BNT162b2 vaccine, containing lipid nanoparticles-formulated mRNA encoding the full-length spike protein of SARS-CoV-2, has been employed to immunize health care workers in Italy, administered in two doses 21 days apart. In this study, we characterized the antibody response induced by the BNT162b2 vaccine in a group of health care workers, tested at baseline, after the first dose and after the booster. Thirty-nine subjects without previous exposure to SARS-CoV-2 were vaccinated with the BNT162b2 vaccine. IgM, IgG, and IgA anti-receptor binding domain (RBD) were tested by ELISA. Neutralizing antibodies were evaluated testing the inhibition of RBD binding to ACE2. Antibody avidity was measured by urea avidity ELISA. IgM anti-RBD are produced after the first dose of vaccine and persist after the booster. IgG and IgA anti-RBD antibodies are detected in high amounts in all the subjects after the first dose and further increase after the booster. A few subjects, already after the first dose, produce antibodies inhibiting RBD interaction with ACE2. After the booster, high levels of inhibitory antibodies are detected in all the subjects. Affinity maturation takes place with boosting and IgG anti-RBD avidity increases with the number of immunizations. A less pronounced increase is observed with IgA. These data indicate that the BNT162b2 vaccine can induce high levels of protective antibodies of high avidity in vaccinated subjects; both IgG and IgA anti-RBD antibodies are produced. Further studies are needed to evaluate antibody persistence over time.

Robust Antibody Levels in Both Diabetic and Non-Diabetic Individuals After BNT162b2 mRNA COVID-19 Vaccination

“…Increased anti-S-RBD IgG antibody titers indicate seroconversion after either disease exposure or immunization ( 24 ). Robust SARS-CoV-2 IgG and neutralizing antibody levels in our study cohort after two doses of BNT162b2 mRNA vaccine suggest proficient antigen processing and presentation in all individuals as indicated by other BNT162b2 vaccination studies in diverse cohorts ( 15 , 25 – 27 ).…”

“…Therefore, sVNT was used and high levels of neutralizing antibodies were detected, indicating that BNT162b2 mRNA vaccine induced protective immunity in these individuals. In line with this, Pratesi et al showed that BNT162b2 mRNA vaccine induced increased levels of highavidity, anti-RBD IgG/IgA, and protective neutralizing antibodies in the vaccinated cohort (15). We further assessed whether presence of T2DM impacted the humoral immune response proficiency in response to BNT162b2 mRNA vaccine.…”

“…In line with this, Pratesi et al. showed that BNT162b2 mRNA vaccine induced increased levels of high-avidity, anti-RBD IgG/IgA, and protective neutralizing antibodies in the vaccinated cohort ( 15 ).…”

“…The vaccine is administered as two shots, intramuscularly, given 3 weeks apart, and has been shown to offer protection by triggering an immune response against infection by the SARS-CoV-2 spike protein. Since BNT162b2 vaccine delivers mRNA encoding only for SARS-CoV-2 spike protein, the expected elicited response is production of anti-S-RBD immunoglobulin G (IgG), IgM, and IgA isotypes, with neutralization potential of inhibiting the RBD binding to ACE2 cognate receptor ( 15 ). As T2DM patients are at higher risk of severe COVID-19 symptoms and mortality, such patients have been prioritized to receive COVID-19 vaccinations ( 16 ).…”

Long-term decay of anti-RBD IgG titers after BNT162b2 vaccination is not mirrored by loss of neutralizing bioactivity against SARS-CoV-2

“…Failure of affinity maturation has been previously associated with vaccine failure [28] and some Authors have advocated that the development of high affinity antibodies targeting multiple epitopes of RBD are needed for effective long-term protection against SARS-CoV-2 [29] , [30] , [31] , [32] . Available studies [30] , [33] , [34] have shown parallel increases in avidity values, neutralizing activity and quantitative anti-RBD antibody titres up to 8 weeks from the second dose of vaccine but these short-term analyses were not designed to prove whether quantitative RBD-antibody level would predict neutralizing bioactivity and clinical protection on the long-term, when divergent kinetics of immunogenicity markers may unmask functional mechanistic associations [16] , [22] .…”