Third-Dose BNT162b2 Vaccination Elicits Markedly High-Level SARS-CoV-2-Neutralizing Antibodies in Vaccinees Who Responded Poorly to a Second Dose in Japan.
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ABSTRACT:
SUBMITTER: Amano M
PROVIDER: S-EPMC9129163 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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Third-Dose BNT162b2 Vaccination Elicits Markedly High-Level SARS-CoV-2-Neutralizing Antibodies in Vaccinees Who Responded Poorly to a Second Dose in Japan.
Amano Masayuki M Maeda Kenji K Tsuchiya Kiyoto K Shimada Shinya S Mitsuya Hiroaki H
The Journal of infectious diseases 20221101 11
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Project description:BackgroundVaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial for ending the pandemic of coronavirus disease 2019 (COVID-19). Currently, the cumulative effect of booster shots of mRNA vaccines on adverse events is not sufficiently characterized.MethodsA survey-based study on vaccine adverse events was conducted in a Japanese medical institute after the third dose of Pfizer BNT162b2. Adverse events were grouped using network analysis, and a heteroscedastic probit model was built to analyse adverse events.ResultsThere were two main clusters of adverse events, systemic and local injection site-associated events. Subject background and the experience of previous vaccine-related adverse events were variably associated with the occurrence and intensity of adverse events following the third dose. Among adverse events, only lymphadenopathy increased prominently following the third dose, while the largest increase in other systemic adverse events occurred generally following the second dose.ConclusionsThe effect of repeated booster vaccines on the frequency and intensity of adverse events differs depending on the kind of adverse event.
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Project description:Hemodialysis patients are at high risk for severe COVID-19, and impaired seroconversion rates have been demonstrated after COVID-19 vaccination. Humoral immunity wanes over time and variants of concern with immune escape are posing an increasing threat. Little is known about protection against the B.1.617.2 (delta) variant of concern in hemodialysis patients before and after third vaccination. We determined anti-S1 IgG, surrogate neutralizing, and IgG antibodies against different SARS-CoV-2 epitopes in 84 hemodialysis patients directly before and three weeks after a third vaccine dose with BNT162b2. Third vaccination was performed after a median (IQR) of 119 (109-165) days after second vaccination. In addition, neutralizing activity against the B.1.617.2 (delta) variant was assessed in 31 seroconverted hemodialysis patients before and after third vaccination. Triple seropositivity for anti-S1 IgG, surrogate neutralizing, and anti-RBD antibodies increased from 31/84 (37%) dialysis patients after second to 80/84 (95%) after third vaccination. Neutralizing activity against the B.1.617.2 (delta) variant was significantly higher after third vaccination with a median (IQR) ID50 of 1:320 (1:160-1:1280) compared with 1:20 (0-1:40) before a third vaccine dose (P<0.001). The anti-S1 IgG index showed the strongest correlation with the ID50 against the B.1.617.2 (delta) variant determined by live virus neutralization (r=0.91). We demonstrate low neutralizing activity against the B.1.617.2 (delta) variant in dialysis patients four months after standard two-dose vaccination but a substantial increase after a third vaccine dose. Booster vaccination(s) should be considered earlier than 6 months after the second vaccine dose in immunocompromised individuals.
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Project description:Transplant recipients, who receive therapeutic immunosuppression to prevent graft rejection, are characterized by high coronavirus disease 2019 (COVID-19)-related mortality and defective response to vaccines. We observed that previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but not the standard two-dose regimen of vaccination, provided protection against symptomatic COVID-19 in kidney transplant recipients. We therefore compared the cellular and humoral immune responses of these two groups of patients. Neutralizing anti-receptor-binding domain (RBD) immunoglobulin G (IgG) antibodies were identified as the primary correlate of protection for transplant recipients. Analysis of virus-specific B and T cell responses suggested that the generation of neutralizing anti-RBD IgG may have depended on cognate T-B cell interactions that took place in germinal center, potentially acting as a limiting checkpoint. High-dose mycophenolate mofetil, an immunosuppressive drug, was associated with fewer antigen-specific B and T follicular helper (TFH) cells after vaccination; this was not observed in patients recently infected with SARS-CoV-2. Last, we observed that, in two independent prospective cohorts, administration of a third dose of SARS-CoV-2 mRNA vaccine restored neutralizing titers of anti-RBD IgG in about 40% of individuals who had not previously responded to two doses of vaccine. Together, these findings suggest that a third dose of SARS-CoV-2 mRNA vaccine improves the RBD-specific responses of transplant patients treated with immunosuppressive drugs.
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