Antibody-dependent neutralizing capacity of the SARS-CoV-2 vaccine BNT162b2 with and without previous COVID-19 priming.
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ABSTRACT:
SUBMITTER: Hansen CB
PROVIDER: S-EPMC8447364 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
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Project description:Each severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant renews concerns about decreased vaccine neutralization weakening efficacy. However, while prevention of infection varies, protection from disease remains and implicates immunity beyond neutralization in vaccine efficacy. Polyclonal antibodies function through Fab domains that neutralize virus and Fc domains that induce non-neutralizing responses via engagement of Fc receptors on immune cells. To understand how vaccines promote protection, we leverage sera from 51 SARS-CoV-2 uninfected individuals after two doses of the BNT162b2 mRNA vaccine. We show that neutralizing activities against clinical isolates of wild-type and five SARS-CoV-2 variants, including Omicron BA.2, link to FcγRIIIa/CD16 non-neutralizing effector functions. This is associated with post-translational afucosylation and sialylation of vaccine-specific antibodies. Further, polyfunctional neutralizing and non-neutralizing breadth, magnitude, and coordination diminish with age. Thus, studying Fc functions in addition to Fab-mediated neutralization provides greater insight into vaccine efficacy for vulnerable populations, such as the elderly, against SARS-CoV-2 and novel variants.
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Project description:We analyzed serially collected serum samples from healthy adults who underwent BNT162b2 vaccination to elucidate the association between spike (S)-IgG antibody titers determined by ELISA using the WHO international standard (NIBSC code 20/136) and neutralizing antibody titers against three live SARS-CoV-2 variants. This study included 53 health care workers who received two doses of the BNT162b2 vaccine. S-IgG and nucleocapsid (N)-IgG antibody titers were measured by ELISA. Neutralizing (NT) antibody responses against three variants (Wuhan D614 G: KUH003, Alpha, and Delta) were evaluated before and after the first and second vaccination. N-IgG were not detected in any serum samples. S-IgG antibody titers remarkably increased after two BNT162b2 vaccine doses in all participants. S-IgG antibody titers were strongly correlated with NT titers against three variants of live viruses: KUH003 (r = 0.86), Alpha (r = 0.72), and Delta (r = 0.84). Serum samples from participants after one dose of BNT162b2 neutralized Alpha efficiently (median titer, 113.0), but median NT titers against KUH003 and Delta variants were lower, 57.0 and 28.0, respectively (p < .01). Two doses of the BNT162b2 vaccine elicited a strong immune response in this study. The second dose was required for induction of a strong booster effect. Serum collected from BNT162b2 vaccine recipients contained significantly lower neutralizing activity against Delta than that of against KUH003 (p < .0001) and Alpha (p < .0001). If a new variant emerges, live virus-based NT titers should be examined in serum obtained from vaccine recipients to evaluate vaccine efficacy for protection against infection.
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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.
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Project description:Backgroundto evaluate whether prior SARS-CoV-2 infection affects side effects and specific antibody production after vaccination with BNT162b2.MethodsWe included 1106 health care workers vaccinated with BNT162b2. We assessed whether prior SARS-CoV-2 infection affects the number and type of side effects and performed a nested case-control analysis comparing plasma levels of specific IgG titers between SARS-CoV-2-naïve and previously infected subjects after the first and the second vaccine doses.ResultsAfter the first dose, SARS-CoV-2-naïve subjects experienced side effects more often than SARS-CoV-2 naïve subjects. Individuals with prior SARS-CoV-2 infection more often reported pain at the injection site, weakness, and fever than SARS-CoV-2-naïve subjects. After the second dose, the frequency of side effects was similar in the two groups. All subjects with prior SARS-CoV-2 infection developed either a high (>100 AU/mL) or intermediate (10-100 AU/mL) antibody titer. Among SARS-CoV-2-naïve subjects, the majority developed an intermediate titer. After the second dose, a high (>2000 AU/mL) antibody titer was more common among subjects with prior SARS-CoV-2 infection.Conclusionsvaccine-related side effects and a higher anti-SARS-CoV-2-RBD IgG titer were more common in subjects with previous infection than in SARS-CoV-2-naïve after the first, but not after the second dose of the BNT162b2 vaccine.
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