Project description:BackgroundPrevious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primes the immune system; thus individuals who have recovered from infection have enhanced immune responses to subsequent vaccination (hybrid immunity). However, it remains unclear how well hybrid immunity induced by severe or mild infection can cross-neutralize emerging variants. We aimed to compare the strength and breadth of antibody responses in vaccinated recovered and uninfected subjects.MethodsWe measured spike-specific immunoglobulin (Ig)G and neutralizing antibodies (NAbs) from vaccinated subjects including 320 with hybrid immunity and 20 without previous infection. From 29 subjects with a previous severe or mild infection, we also measured NAb responses against Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529/BA.1) variants following vaccination.ResultsA single vaccine dose induced 2-fold higher anti-spike IgG concentrations and up to 4-fold higher neutralizing potency of antibodies in subjects with a previous infection compared with vaccinated subjects without a previous infection. Hybrid immunity was more enhanced after a severe than a mild infection, with sequentially decreasing NAb titers against Alpha, Beta, Delta, and Omicron variants. We found similar IgG concentrations in subjects with a previous infection after 1 or 2 vaccine doses.ConclusionsHybrid immunity induced strong IgG responses, particularly after severe infection. However, the NAb titers were low against heterologous variants, especially against Omicron.
Project description:Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable "sterilizing immunity" at the mucosal level. Our study uncovers a strong temporary neutralizing mucosal component of immunity, emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate that these IgAs mediate neutralization. RBD-targeting IgAs were found to associate with the secretory component, indicating their bona fide transcytotic origin and their polymeric multivalent nature. The mechanistic understanding of the high neutralizing activity provided by mucosal IgA, acting at the first line of defense, will advance vaccination design and surveillance principles and may point to novel treatment approaches and new routes of vaccine administration and boosting.
Project description:We evaluated the post-booster (BNT162b2) antibody responses in Singapore. Participants (n = 43) were tested pre-booster and 20/30/60/90 days post-booster. Participants were boosted 120-240 days (mean 214 days) after their second dose and had no history or serologic evidence of prior COVID-19 infection; all participants had undetectable SARS-CoV-2 nucleocapsid antibodies throughout the study. Total nucleocapsid and spike antibodies (S-Ab) were assessed on the Roche Elecsys e802 and neutralizing antibody (N-Ab) on the Snibe quantitative N-Ab assay. Pre-booster median S-Ab/N-Ab titers were 829 BAU/mL/0.83 µg/mL; 2 participants were below manufacturer's N-Ab cut-offs of 0.3 µg/mL (0.192 and 0.229). Both S-Ab and N-Ab titers peaked at 30 days post-booster (median S-Ab 25,220 BAU/mL and N-Ab 30.3 µg/mL) at 30-37× pre-booster median levels. These peak post-booster S-Ab/N-Ab titers were 11× (25,220 vs. 2235 BAU/mL) and 9× (30.3 vs. 3.52 µg/mL) higher than the previously reported peak post-second dose levels. Antibody titers declined to 12,315 BAU/mL (51% decrease) and 14.3 µg/mL (53% decrease) 90 days post-booster. Non-linear regression estimates for S-Ab/N-Ab half-lives were 44/58 days. At 180 days post-booster, S-Ab/N-Ab are estimated to be 2671 BAU/mL/4.83 µg/mL. Both S-Ab and N-Ab show a good response following post-booster vaccination, with half-lives that may provide a prolonged antibody response.
Project description: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.
Project description:The main expected result of a vaccine against viruses is the ability to produce neutralizing antibodies. Currently, several vaccines against SARS-CoV-2 are being applied to prevent mortal complications, being Pfizer-BioNTech (BNT162b2) one of the first to be authorized in the USA and Mexico (11 December 2020). This study evaluated the efficacy of this vaccine on antibody production with neutralizing capacity and its side effects in healthcare workers with and without prior SARS-CoV-2 infection and in a group of unvaccinated individuals with prior COVID-19. The main findings are the production of 100% neutralizing antibodies in both groups after the second dose, well-tolerated adverse effects, the possible presence of immunosenescence, and finally, we support that a single dose of this vaccine in individuals with prior COVID-19 would be sufficient to achieve an immunization comparable to people without prior COVID-19 with a complete vaccination program (2 doses).
Project description:In a cohort of BNT162b2 (Pfizer-BioNTech) mRNA vaccine recipients (n = 1,090), we observed that spike-specific IgG antibody levels and ACE2 antibody binding inhibition responses elicited by a single vaccine dose in individuals with prior SARS-CoV-2 infection (n = 35) were similar to those seen after two doses of vaccine in individuals without prior infection (n = 228). Post-vaccine symptoms were more prominent for those with prior infection after the first dose, but symptomology was similar between groups after the second dose.