Project description:ObjectivesThe recent surge in coronavirus disease 2019 cases led to the consideration of a booster vaccine in previously vaccinated immunosuppressed individuals. However, the immunogenic effect of a third-dose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in immunosuppressed patients is still unknown.MethodsThis was an observational cohort study of 279 previously vaccinated immunosuppressed patients followed at a single tertiary hospital in Israel. Patients were administered a third dose of the Pfizer-BioNTech mRNA vaccine (BNT162b2) between July 14 and July 21, 2021. Levels of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 were measured 3 to 4 weeks after vaccination.ResultsOf the cohort of 279 patients, 124 (44.4%) had haematologic malignancies, 57 (20.4%) had rheumatologic diseases, and 98 (35.1%) were solid organ-transplant recipients. Anti-SARS-CoV-2 antibody levels increased in 74.9% of cases. Across the entire cohort, the median absolute antibody levels (expressed in AU/mL) increased from 7 (interquartile range (IQR), 0.1-69) to 243 (IQR, 2-4749) after the booster dose. The response significantly varied across subgroups: The transplant cohort showed the greatest increase in absolute antibody levels (from 52 (IQR, 7.25-184.5) to 1824 (IQR, 161-9686)), followed by the rheumatology (from 22 (IQR, 1-106) to 1291 (IQR, 6-6231)) and haemato-oncology (from 1 (IQR, 0.1-7) to 7.5 (IQR, 0.1-407.5)) cohorts. The χ2 test was 8.30 for difference in fold change (p = 0.016). Of the 193 patients who were seronegative at baseline, 76 became seropositive after vaccination, corresponding to a 39.4% (95% CI, 32.8%-46.4%) seroconversion rate. Transplant patients had the highest seroconversion rate (58.3% (95% CI, 44.3%-71.2%)), followed by rheumatology (44.1% (95% CI, 28.9%-60.5%)) and haemato-oncology (29.7% (95% CI, 22%-38.8%); χ2 = 11.87; p = 0.003) patients.DiscussionA third dose of BNT162b2 is immunogenic in most immunosuppressed individuals, although antibody response may differ based on the type of disease and immunosuppression. The antibody level that correlates with protection is still unknown; thus, future studies are needed to evaluate clinical outcomes.
Project description:Rationale & objectiveRecent studies showed that antibody titers after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the dialysis population are diminished as compared with the general population, suggesting the possible value of a third booster dose. We characterized the humoral response after 3 doses of the BNT162b2 vaccine in patients treated with either maintenance hemodialysis (HD) or peritoneal dialysis (PD).Study designCase series.Setting & participants69 French patients (38 HD and 31 PD) treated at a single center who received 3 doses of the BNT162b2 vaccine.FindingsHumoral response was evaluated using plasma levels of anti-SARS-CoV-2 spike protein S1 immunoglobulin measured after the second dose and at least 3 weeks after the third dose of the BNT162b2 vaccine. Patients (median age 68 years [interquartile range (IQR), 53-76 years], 65% men) had a median anti-S1 antibody level of 284 [IQR, 83-1190] AU/mL after the second dose, and 7,554 [IQR, 2,268-11,736] AU/mL after the third dose. Three patients were nonresponders (anti-S1 antibody level < 0.8 AU/mL), and 12 were weak responders (anti-S1 antibody level 0.8-50 AU/mL) after the second vaccine dose. After the third dose, 1 of the 3 initial nonresponders produced anti-spike antibody, and all the 12 initial weak responders increased their antibody levels. Patients with a greater increase in anti-S1 antibody levels after a third dose had lower antibody levels after the second dose, and a longer time interval between the second and the third dose. Adverse events did not seem to be more common or severe after a third vaccine dose.LimitationsObservational study, small sample size. Relationship between antibody levels and clinical outcomes is not well understood.ConclusionsA third dose of the BNT162b2 vaccine substantially increased antibody levels in patients receiving maintenance dialysis and appeared to be as well tolerated as a second dose.
Project description:The first SARS-CoV-2 vaccination campaign in Turkey has started in mid-January for the healthcare workers (HCWs) with the inactive virus vaccine CoronaVac (Sinovac). After four and a half months, the Turkish Ministry of Health rolled out a booster-dose vaccination campaign for HCWs and all people over 50 years old beginning in July 2021. The individuals eligible were given the choice of either CoronaVac or mRNA vaccine BNT162b2 for the third booster-dose vaccination. This study aimed to evaluate SARS-CoV-2 IgG antibody titers against the S1 subunit of the spike protein as a marker of the humoral response in 179 HCWs who received a third booster dose of either CoronaVac or BNT162b2. A total of 136 HCWs, 71 female (52.2%) and 65 male (47.8%), completed both serum collections on Days 0 and 28. The median SARS-CoV-2 IgG S Protein (SP) titer in all participants before the vaccination was 175.7 AU/ml. Of 136 HCWs, 103 (75.73%) chose BNT162b2 vaccine and 33 (24.26%) chose CoronaVac as the third booster dose. There was a significant difference between the BNT162b2 group and the CoronaVac group in terms of SARS-CoV-2 IgG SP titers (p < 0.001). The median SARS-CoV-2 IgG SP titers in BNT162b2 group (n = 103) and in CoronaVac group (n = 33) were 17619.3 AU/ml and 1153.0 AU/ml, respectively. The third booster dose with BNT162b2 and CoronaVac increased antibody titers in each participant a mean of 162-fold and 9-fold, respectively. HCWs in the BNT162b2 group reported more frequent adverse events than HCWs in the CoronaVac group (p < 0.001).
Project description:This study monitored the anti-spike-receptor-binding domain (RBD) and neutralizing antibodies induced by the Pfizer/BioNTech mRNA BNT162b2 vaccine in a cohort of 163 healthcare workers aged ≤60 years. We have taken advantage of two study groups, both of whom received the first two doses in the same time window, but Group 1 (54 HCWs) received the third dose 2 months before Group 2 (68 HCWs) did. The cohorts were monitored from the 12th day after the first vaccine dose up to 1 month after the third vaccine dose for a total of eight time points and about 1 year of surveillance (T1 = 12 days after the first dose; T2 = 10 days after the second dose; T3 = 1 month after the second dose; T4 = 3 months after the second dose; T5 = 4 months after the second dose; T6 = 5 months after the second dose; T7 = 7 months after the second dose; T8 = 1 month after the third dose for Group 1; T8* = 9 months after the second dose for Group 2; T9 = 1 month after the third dose for Group 2). The mean value of anti-spike antibodies decreased faster over time, but at T7, its decline was significantly slowed (T7 vs. T8*). After the third dose, the anti-spike titer rose about 34-fold (T7 vs. T8 and T8* vs. T9) and the booster improved the anti-spike titer by about three times compared with that of the second dose (T3 vs. T8 and T3 vs. T9), and no difference was noted between the two groups. The neutralizing titer was evaluated at T3, T7, T8, and T9. Anti-spike and neutralizing antibodies were found to be strongly correlated (r2 = 0.980; p < 0.001). At T3, 70% of the participants had a neutralizing antibody titer >91% of total anti-spike antibodies that increased to 90% after the third dose (T8 and T9). However, when the anti-spike titer reached its lowest value (T7), the neutralizing antibody levels decreased even further, representing only 44% of total anti-spike antibodies (p < 0.0001). Our findings show that the third vaccine dose improves the humoral response, but the wane of the anti-spike and neutralizing antibody titers over time is more marked in the neutralizing antibodies.
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.
Project description:PurposeAdministration of three doses of Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine was completed in Japan in the spring of 2022. This study aimed to evaluate the antibody responses, and kinetics of three doses of vaccine in healthcare workers (HCWs).Patients and methodsWe conducted a longitudinal cohort study with HCWs, who had no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, from a single hospital. Immunoglobulin G (IgG) titers of anti-SARS-CoV-2 spike protein (SP) and nucleocapsid protein (NP) titers were measured using an automated chemiluminescent enzyme immunoassay system.ResultsA total of 636 HCWs participated in the study. The anti-SP IgG titers decreased slowly after the second dose of the BNT162b2 vaccine in all participants, and robust antibody response was observed after the third dose of the vaccine. The peak anti-SP IgG titer after the third dose was approximately 4.1-fold higher than that after the first and second doses, and the rate of decrease in the anti-SP IgG titer after the third dose was significantly more gradual, than that after the second dose. After the second dose of vaccine, the antibody response was weaker in older participants than in younger participants, and in males than in females respectively, whereas the response to the third dose of vaccine did not differ significantly by sex or age. Adverse events following immunization were generally mild to moderate.ConclusionThe third dose of the BNT162b2 vaccine induced a significant and sustained increase in anti-SP IgG titers, and was generally safe and well-tolerated.
Project description:BackgroundVaccination is our main strategy to control SARS-CoV-2 infection. Given the decrease in quantitative SARS-CoV-2 spike 1-2 IgG antibody titers three months after the second BNT162b2 dose, healthcare workers received a third booster six months after completing the original protocol. This study aimed to analyze the quantitative SARS-CoV-2 spike 1-2 IgG antibody titers and the safety of the third dose.Material and methodsA prospective longitudinal cohort study included healthcare workers who received a third booster six months after completing the BNT162b2 regimen. We assessed the quantitative SARS-CoV-2 spike 1-2 IgG antibody titers 21-28 days after the first and second dose, three months after the completed protocol, 1-7 days following the third dose, and 21-28 days after booster administration.ResultsThe cohort comprised 168 participants aged 41(10) years old, 67% of whom were female. The third dose was associated with an increase in quantitative antibody titers, regardless of previous SARS-CoV-2 history. In cases with a negative SARS-CoV-2 history, the median (IQR) antibody titer values increased from 379 (645.4) to 2960 (2010) AU/ml, whereas in cases with a positive SARS-CoV-2 history, from 590 (1262) to 3090 (2080) AU/ml (p<0.001). The third dose caused a lower number of total (local and systemic) adverse events following immunization (AEFI) compared with the first two vaccines. However, in terms of specific symptoms such as fatigue, myalgia, arthralgia, fever, and adenopathy, the proportion was higher in comparison with the first and second doses (p<0.05). The most common AEFI after the third BNT162b2 vaccine was pain at the injection site (n = 82, 84.5%), followed by fatigue (n = 45, 46.4%) of mild severity (n = 36, 37.1%).ConclusionThe third dose applied six months after the original BNT162b2 regimen increased the quantitative SARS-CoV-2 spike 1-2 IgG antibody titers. The booster dose was well tolerated and caused no severe AEFI.