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Objectives: Administration of the third dose of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine was initiated on December 1, 2021, in Japan. However, data on the long-term effects of this third vaccination remain scarce. Here, we examined the levels of SARS-CoV-2 antibodies in those who received the Pfizer BioNTech (BNT162b2) vaccine, 6 months after the third vaccination. Method(s): Samples from 40 healthy volunteers were used to measure SARS-CoV-2 antibodies with chemiluminescent assays against the receptor-binding domain (RBD) of the virus. Result(s): At 445 days after the first dose of BNT162b2, which is 180 days after the third vaccination, the mean anti-RBD IgG level was 159.4 AU/mL (SD 100.1 AU/mL), which was significantly higher than 144 days after the second vaccination, while mean anti-RBD IgM was baseline level (0.4 C.O.I.). The decline in IgG, 180 days after the third vaccination, was 74.1% (SD 16.1%), which was significantly lower than the 88.6% (SD 4.4%) decline observed 144 days after the second vaccination. Furthermore, we revealed that the reduction in IgG from 14 to 180 days after the third vaccination showed a significant inverse correlation with age, and the higher antibody response in younger participants at 14 days after the third vaccination disappeared at longer time points. Conclusion(s): The long-term durability of the IgG titer was significantly higher following the third vaccination compared with the second vaccination, and the reduction in IgG titer after the third vaccination inversely correlated with age.Copyright © 2022 the author(s), published by De Gruyter, Berlin/Boston.
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Patients with B-cell malignancies are at a higher risk of severe SARS-CoV-2 infections. Nevertheless, extensive data on the immune responses of hematological patients and the efficacy of the third dose of the vaccine are scarce. The goal of this study was to determine standardized anti-SARS-CoV-2 S antibody levels and to evaluate differences between treatment modalities in response to the second and third vaccines among patients with B-cell malignancies treated at the University Hospital Krems and the University Hospital of Vienna. The antibody levels of a total of 80 patients were retrospectively analyzed. The results indicate a significant increase in antibody production in response to the third vaccination. The highest increases could be observed in patients in a "watchful-waiting" and "off-therapy" setting. Encouragingly, approximately one-third of patients who did not develop antibodies in response to two vaccinations achieved seroconversion after the third vaccination. "Watchful-waiting", "off-therapy" and treatment with BTK inhibitors were indicative for increased antibody response after the third dose compared to anti-CD19 CAR T-cell and anti-CD-20 antibody treatment. In summary, the results of this study underline the pre-eminent role of the need for complete vaccination with three doses for the development of protective immunity in patients with B-cell malignancies.
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BACKGROUND: Booster vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being promoted worldwide to counter the coronavirus disease 2019 (COVID-19) pandemic. In this study, we analyzed the longitudinal effect of the third BNT162b2 mRNA vaccination on antibody responses in healthcare workers. Additionally, antibody responses induced by the fourth vaccination were analyzed. METHODS: The levels of anti-spike (S) IgG and neutralizing antibody against SARS-CoV-2 were measured at 7 months after the second vaccination (n = 1138), and at 4 (n = 701) and 7 (n = 417) months after the third vaccination using an iFlash 3000 chemiluminescence immunoassay analyzer. Among the 417 participants surveyed at 7 months after the third vaccination, 40 had received the fourth vaccination. A multiple linear regression analysis was performed to clarify which factors were associated with the anti-S IgG and neutralizing antibody. Variables assessed included sex, age, number of days after the second or third vaccination, diagnostic history of COVID-19, and anti-nucleocapsid (N) IgG level. RESULTS: At 7 months after the third vaccination, antibody responses were significantly higher than those at the same time after the second vaccination. Unlike the second vaccination, age had no effect on the antibody responses induced by the third vaccination. Furthermore, the fourth vaccination resulted in a further increase in antibody responses. The multiple linear regression analysis identified anti-N IgG level, presumably associated with infection, as a factor associated with antibody responses. CONCLUSIONS: Our findings showed that BNT162b2 booster vaccinations increased and sustained the antibody responses against SARS-CoV-2.
Subject(s)
BNT162 Vaccine , COVID-19 , Humans , Japan , Tokyo , Antibody Formation , COVID-19/prevention & control , SARS-CoV-2/genetics , Health Personnel , Antibodies, Neutralizing , RNA, Messenger , Vaccination , Immunoglobulin G , Antibodies, ViralABSTRACT
The efficacy of the COVID-19 mRNA vaccine, including the third vaccination in pediatric inflammatory bowel disease (PIBD) patients is not fully understood. This study aimed to evaluate the humoral immunogenicity of the BNT162b2 vaccine and the changes in durability until 20-28 weeks after the initial vaccine series in PIBD patients on immunosuppressive drugs. The safety of the initial vaccine series and the booster effect of the third vaccination were also evaluated. A single-center, prospective cohort study was conducted, and 63 participants (anti-TNFα: 11; non-anti-TNFα: 31; 5-ASA: 21), with a mean age of 15.2 (range 9.6-17.9) years, were enrolled. All PIBD patients were seroconverted, with no serious short-term AEs. PIBD patients on anti-TNFα had significantly lower antibody titers than those on other medications at all measurement points. Furthermore, antibody titers waned over time with anti-TNFα and were significantly lower at 20-28 weeks than at 3-9 weeks after a two-vaccine series. In all 10 patients (anti-TNFα: 5; non-anti-TNFα including 5-ASA: 5), the third vaccination led to antibody concentrations significantly higher than those at the same time point after the second vaccination. PIBD patients on anti-TNFα need to remain vigilant about COVID-19 even after two vaccinations, and a third vaccination may be considered.
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[This corrects the article DOI: 10.3389/fmed.2022.936126.].
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Response to SARS-CoV-2-vaccines in kidney-transplant recipients (KTR) is severely reduced. Heterologous3rd vaccination combining mRNA and vector vaccines did not increase seroconversion at 4 weeks after vaccination, but evolution of antibody levels beyond the first month remains unknown. We have recently completed a randomized-controlled trial on heterologous (Ad26COVS1) vs. homologous (BNT162b2 or mRNA-1273) 3rd vaccination in 201 KTR not developing SARS-CoV-2-spike-protein antibodies following two doses of mRNA vaccine (EurdraCT: 2021-002927-39). Here, we report seroconversion at the second follow-up at 3 months after the 3rd vaccination (prespecified secondary endpoint). In addition, higher cut-off levels associated with neutralizing capacity and protective immunity were applied (i.e., > 15, > 100, > 141, and > 264 BAU/ml). A total of 169 patients were available for the 3-month follow-up. Overall, seroconversion at 3 months was similar between both groups (45 vs. 50% for mRNA and the vector group, respectively; p = 0.539). However, when applying higher cut-off levels, a significantly larger number of individuals in the vector group reached antibody levels > 141 and > 264 BAU/ml at the 3-month follow-up (141 BAU/ml: 4 vs. 15%, p = 0.009 and 264 BAU/ml: 1 vs. 10%, p = 0.018 for mRNA vs. the vector vaccine group, respectively). In line, antibody levels in seroconverted patients further increased from month 1 to month 3 in the vector group while remaining unchanged in the mRNA group (median increase: mRNA = 1.35 U/ml and vector = 27.6 U/ml, p = 0.004). Despite a similar overall seroconversion rate at 3 months following 3rd vaccination in KTR, a heterologous 3rd booster vaccination with Ad26COVS1 resulted in significantly higher antibody levels in responders.
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INTRODUCTION: Lung transplant recipients (LuTX) represent a vulnerable population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though many vaccines are already developed, more clinical data need to support effective immunological response in immunocompromised patients. METHODS: Stable LuTX recipients with no medical history of coronavirus disease (COVID-19) were enrolled. Currently available messenger RNA (mRNA) (BNT162b2-mRNA, mRNA-1273) and non-mRNA (ChAdOx1, BBIBP-CorV) vaccines were given according to availability, boosters were all mRNA-based. SARS-CoV-2 Spike1 immunoglobulin G (IgG) antibody titer was evaluated before and 2 weeks after second and third dose. Difference between mRNA versus non-mRNA vaccines was assessed. RESULTS: Forty-one patients (49% men, age 48.4 ± 13.8 years) received two doses of SARS-CoV-2 vaccines: 23 of mRNA, 18 of non-mRNA, and 24/41 (58%) received a third dose. Median 92 months passed since transplantation, and serum level of tacrolimus was median 5.5 ng/ml. Positive serology was found in 37% of all patients after the second dose, 86% had mRNA vaccine. After the third dose, 29% became positive who had no antibody before. Significantly higher level of antibody was found after the second mRNA than non-mRNA vaccines (2.2 vs. 1568.8 U/ml, respectively, p = .002). 6/23 (26%) patients received two doses of mRNA vaccine developed COVID-19 after the second injection in an average of 178 days, half of them recovered, half of them died in intensive care unit (ICU). 3/6 (50%) patients with two doses mRNA and recovered from COVID-19 had significantly higher level of antibody (average 20847.3 U/ml) than without infection. After the booster vaccine, 1/24 (4%) developed infection. CONCLUSION: Immunosuppression therapy may induce a weaker SARS-CoV-2 response in LuTX recipients; therefore, third dose is a priority in transplanted patients. The highest antibody level was measured recovering from COVID after two doses. Our data confirm that booster mRNA vaccine could increase antibody levels, even if immunization was started with non-mRNA vaccine.
Subject(s)
BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Transplant Recipients , Adult , Antibodies, Viral , BNT162 Vaccine/adverse effects , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Humans , Lung , Male , Middle Aged , SARS-CoV-2 , Viral Vaccines/adverse effectsABSTRACT
Third dose of SARS-CoV-2 vaccination was started from December 1, 2021 in Japan. However, data on the precise analysis of the side effects after third vaccination, remain scarce. Here, we examined the side effects and the levels of SARS-CoV-2 IgG antibody in healthy volunteers who underwent BNT162b2 vaccination.Forty-one healthy volunteers were assessed for the side effects of the vaccination for the third dose, and samples were used for the measurement of SARS-CoV-2 IgG antibody with chemiluminescent assays against the Receptor Binding Domain (RBD) of the virus.We analyzed the humoral responses and found that the IgG levels showed clear declining trends with age. Commonly reported side effects in the participants after the third dose were similar to those in second dose, such as, generalized weakness/fatigue (65.9%), headache (58.5%), and sore arm/pain (87.8%). The frequency of the fever was slightly less (39.0%), compared to the second dose (57.5%), but localized symptoms, such as itching (14.6%) and lymphadenopathy (14.6%) were not negligible, which were not seen at the second dose. The number of side effects were tended to be decreased with age.The production of IgG after the third doses of BNT162b2 vaccination decreases age-dependently. The number of side effects were tended to be decreased with age. The high frequencies of generalized weakness/fatigue, fever, and sore arm/pain were not negligible, after the third dose.
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Emerging numbers of SARS-CoV-2 infections are currently combated with a third vaccination. Considering the different vaccination regimens used for the first two vaccine doses, we addressed whether the previous vaccination influences the immune response to the booster. Participants for this prospective study were recruited from among healthcare workers. N = 20 participants were previously vaccinated with two doses of BNT162b2, and n = 53 received a priming dose of ChAdOx1-nCoV-19 followed by a BNT162b2 dose. Participants were vaccinated with a third dose of BNT162b2 in December 2021. Antibody concentrations were determined after vaccination, and in a subset of n = 19 participants, T cell responses were evaluated. Anti-S concentrations and IFNγ production increased during the first 21 days. The choice of the first and second vaccineshad no influence on the final outcome of the booster vaccination. Before booster vaccination, antibody concentrations were lower for older participants but increased more strongly over time.