Examining the association between vaccine reactogenicity and antibody titer dynamics after the third dose of BNT162b2 vaccine using a mixed-effects model

BackgroundTo mitigate the COVID-19 pandemic, many countries have recommended the use of booster vaccinations. The relationship between the degree of adverse vaccine reactions and elevated antibody titers is of interest; however, no studies have investigated the temporal changes in antibody titers based on repeated measurements after a third dose of the BNT162b2 vaccine.MethodsThis prospective longitudinal cohort study was conducted with 62 healthcare workers who received a third dose of the BNT162b2 at Okayama University Hospital, Japan. Venous blood draw and fingertip whole blood test sample collection were conducted at the early (3–13 days) and 1-month time points; only FWT sample collection was conducted at the 2-month time point. Information on adverse reactions within 1 week after vaccination was also obtained. The association between fever of 37.5 °C or higher and antibody titers after the third dose of BNT162b2 was examined using a mixed-effects model and Poisson regression with robust variance.ResultsA trend toward higher antibody titers in the early period after vaccination was observed in the febrile individuals, but the differences were not significant at 1 and 2 months post-vaccination (the partial regression coefficient for fever was 8094.3 [-1910.2, 18,098.8] at 1 month after vaccination, and 1764.1 [-4133.9, 7662.1] at 2 months after vaccination in the adjusted models).ConclusionThe findings suggest that the presence of fever after the third vaccine does not predict a sustained elevation in serum antibody titers.     

Immunological responses following the third dose of the BNT162b2 SARS-CoV-2 vaccine among Japanese healthcare workers

IntroductionA limited number of studies have shown a decline in antibody titers in healthcare workers beyond six months after the second dose of the BNT162b2 vaccine, and has been insufficiently investigated yet in the respective Asian ethnic groups.MethodsWe conducted a longitudinal observational study on 187 healthcare workers and other personnel and healthy adults at least eight months after vaccination at the International University of Health and Welfare.ResultsThe baseline (before the third dose of BNT162b2) anti-receptor binding domain (RBD) IgG level was 569[377–943] AU/mL 245[240–250] days after the second dose. The mean antibody titer of participants aged 20–29 years was 4.6 times higher than that of participants aged 70–79 years. After booster vaccination, serum anti-RBD antibody levels were elevated in all participants with a median titer of 23,250[14,612–33,401] AU/mL 21[19–23] days after the third dose. The median post-booster antibody titers in the 20–29, 30–39, 40–49, 50–59, 60–69, and 70–79 years age groups were 30.6, 33.0, 33.8, 27.4, 50.1, and 90.3 times, respectively, higher than the pre-booster ones. Antibody levels were 15% lower in daily drinkers compared to nondrinkers, suggesting that daily alcohol consumption can prevent antibody levels from increasing after vaccination. Our results show decreased antibody titers after two doses of the vaccine, especially in the elderly; however, the third dose of the vaccine resulted in a significant increase in antibody titers in all age groups.ConclusionsWe provided information on antibody responses following primary and booster doses of the BNT162b2 mRNA COVID-19 vaccine in Japan.     

Antibody responses and SARS-CoV-2 infection after BNT162b2 mRNA booster vaccination among healthcare workers in Japan

IntroductionVaccine effectiveness against SARS-CoV-2 infections decreases due to waning immunity, and booster vaccination was therefore introduced. We estimated the anti-spike antibody (AS-ab) recovery by booster vaccination and analyzed the risk factors for SARS-CoV-2 infections.MethodsThe subjects were health care workers (HCWs) in a Chiba University Hospital vaccination cohort. They had received two doses of vaccine (BNT162b2) and a booster vaccine (BNT162b2). We retrospectively analyzed AS-ab titers and watched out for SARS-CoV-2 infection for 90 days following booster vaccination.ResultsAS-ab titer eight months after two-dose vaccinations had decreased to as low as 587 U/mL (median, IQR (interquartile range) 360–896). AS-ab titer had then increased to 22471 U/mL (15761–32622) three weeks after booster vaccination. There were no significant differences among age groups.A total of 1708 HCWs were analyzed for SARS-CoV-2 infection, and 48 of them proved positive. SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 1.8% and 4.0%, respectively, and were not significant. However, when restricted to those 20–29 years old, SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 2.9% and 13.6%, respectively (p = 0.04). After multivariate logistic regression, COVID-19 wards (adjusted odds ratio (aOR):2.9, 95% confidence interval (CI) 1.5–5.6) and those aged 20–49 years (aOR:9.7, 95%CI 1.3–71.2) were risk factors for SARS-CoV-2 infection.ConclusionsBooster vaccination induced the recovery of AS-ab titers. Risk factors for SARS-CoV-2 infection were HCWs of COVID-19 wards and those aged 20–49 years. Increased vaccination coverage, together with implementing infection control, remains the primary means of preventing HCWs from SARS-CoV-2 infection.     

Safety and immunogenicity of the COVID-19 vaccine BNT162b2 in patients undergoing chemotherapy for solid cancer

BackgroundAlthough COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported.MethodsWe investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination.ResultsAnti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063–1.205] and 0.161 [0.07–0.857] vs 0.644 [0.259–1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups.ConclusionAlthough there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.     

Dynamics of anti-Spike IgG antibody level after the second BNT162b2 COVID-19 vaccination in health care workers

IntroductionMany countries are administering a third dose of COVID-19 vaccines, but the evaluation of vaccine-induced immunity is insufficient. In addition, there are few reports of long-term observation of anti-spike IgG antibody titers after the vaccination in the Japanese population. This study aimed to evaluate anti-spike IgG levels in the Japanese health care workers six months after the BNT162b2 vaccination.MethodsDynamics of anti-spike IgG levels were assessed over a six-month period following the second vaccination in 49 participants (Analysis-1). A cross-sectional assessment of anti-spike IgG levels six months after the second vaccination was performed in 373 participants (Analysis-2).ResultsIn Analysis-1, the geometric mean titer of anti-spike IgG was lower in the older age group and decreased consistently after the second vaccination regardless of age. In Analysis-2, the anti-spike IgG level was significantly negatively associated with age (r = ?0.35, p < 0.01). This correlation remained statistically significant (r = ?0.28, p < 0.01) after adjustment for sex, BMI, smoking habits, alcohol drinking habits, allergies, and fever or other adverse reactions at the time of vaccination. Additionally, participants who drank alcohol daily had significantly lower anti-spike IgG levels than participants who had never drunk alcohol. Sex, smoking habits, allergy, and fever and other side effects after vaccination did not show a significant association with anti-spike IgG levels.ConclusionsSix months post-vaccination, the anti-spike IgG level was substantially lower in older persons and daily alcohol drinkers. This may be an indication for an additional vaccine dose for these at-risk categories.     

First-dose mRNA vaccination is sufficient to reactivate immunological memory to SARS-CoV-2 in subjects who have recovered from COVID-19

The characterization of the adaptive immune response to COVID-19 vaccination in individuals who recovered from SARS-CoV-2 infection may define current and future clinical practice. To determine the effect of the 2-dose BNT162b2 mRNA COVID-19 vaccination schedule in individuals who recovered from COVID-19 (COVID-19–recovered subjects) compared with naive subjects, we evaluated SARS-CoV-2 Spike–specific T and B cell responses, as well as specific IgA, IgG, IgM, and neutralizing antibodies titers in 22 individuals who received the BNT162b2 mRNA COVID-19 vaccine, 11 of whom had a previous history of SARS-CoV-2 infection. Evaluations were performed before vaccination and then weekly until 7 days after second injection. Data obtained clearly showed that one vaccine dose is sufficient to increase both cellular and humoral immune response in COVID-19–recovered subjects without any additional improvement after the second dose. On the contrary, the second dose proved mandatory in naive subjects to further enhance the immune response. These findings were further confirmed at the serological level in a larger cohort of naive (n = 68) and COVID-19–recovered (n = 29) subjects, tested up to 50 days after vaccination. These results question whether a second vaccine injection in COVID-19–recovered subjects is required, and indicate that millions of vaccine doses may be redirected to naive individuals, thus shortening the time to reach herd immunity.     

The Israeli study of Pfizer BNT162b2 vaccine in pregnancy: considering maternal and neonatal benefits

Pregnant patients with COVID-19 are more likely to require intensive care and die compared with noninfected pregnant women. While the consequences of COVID-19 disease in pregnancy prompted many health care organizations to support vaccination in pregnancy, vaccine effects for mother and infant remained unclear. In this issue of the JCI, Beharier and Mayo et al. explored maternal and neonatal responses to the Pfizer BNT162b2 SARS-CoV-2 mRNA vaccine. The authors examined blood samples from women and cord blood of neonates following childbirth. Samples were stratified into three groups: vaccine recipients, unvaccinated participants with past positive SARS-CoV-2 test, and unvaccinated participants without prior infection. Vaccinated mothers and mothers with previous infection generated and transferred protective IgG antibodies across the placenta. This study provides evidence to support the safety and efficacy of COVID-19 vaccination in pregnancy with protection to the neonate against infection, outlining clear vaccine benefits for both maternal and child health.     

Antibody response to third and fourth BNT162b2 mRNA booster vaccinations in healthcare workers in Tokyo,Japan

BackgroundBooster 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.MethodsThe 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.ResultsAt 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.ConclusionsOur findings showed that BNT162b2 booster vaccinations increased and sustained the antibody responses against SARS-CoV-2.     

Antibody response after COVID-19 vaccine BNT162b2 on health care workers in Japan

BackgroundVaccination is one of the most important tools to control the COVID-19 pandemic. However, there is little information on the antibody response in humans after the COVID-19 vaccination.MethodsThis single-center, prospective study was conducted in Yokohama, Japan. We included health care workers who had received two doses of COVID-19 vaccination (BNT162b2) 21 days apart. We measured serum immunoglobulin G (IgG) to nucleoprotein and spike protein of SARS-CoV-2 with commercially available kits before and 7, 14, and 35 days after the first dose of vaccination.ResultsA total of 104 workers participated in this study. Of these, 7 participants were seropositive with antibodies to spike protein at baseline and 4 of the 7 seropositive participants had COVID-19 history. The mean level of IgG to spike protein (QT) was 45.2, 1219, 2845, and 23489 AU/mL at baseline, on days 7, 14, and 35, respectively, although the values for nucleoprotein (NG) were 0.2, 0.21, 0.22, and 0.19 S/C, respectively. On day 7, QT in seropositive participants at baseline was elevated, whereas it was not elevated in seronegative participants at baseline until day 14.ConclusionsQT was elevated over the cutoff in all the participants at day 35, but NG did not change between baseline and day 35.     

Efficacy and safety of mRNA SARS-CoV-2 vaccines in lung transplant recipients

BackgroundTo date, reports addressing the antibody response following mRNA SARS-CoV-2 vaccination in lung transplant (LTX) recipients are limited. Thus, the aim of this clinical study was to investigate the efficacy and safety of the vaccines in LTX recipients compared to controls.MethodsAn open-label, nonrandomized prospective study was conducted at Tohoku University Hospital. LTX recipients and controls who received either the BNT162b2 vaccine or the mRNA-1273 vaccine were recruited, and SARS-CoV-2 IgG was measured before and after vaccination. The adverse events were reviewed. Predictors of negative serology after vaccination were evaluated with logistic regression.ResultsForty-one LTX recipients and 24 controls were analyzed. Although all controls had a positive antibody response to a SARS-CoV-2 mRNA vaccine, antibody response was found in 24.4% of LTX recipients (p < .0001). The amount of SARS-CoV-2 IgG following the 2nd dose significantly climbed to 6557 AU/mL in controls, whereas the increase in IgG in LTX recipients was 8.3 AU/mL (p < .0001). Fewer LTX recipients developed systemic fever than controls (p < .0001) despite equivalent overall adverse event percentages in both groups. A higher plasma concentration of mycophenolate was a significant predictor of negative serology (p = .032).ConclusionsAn impaired antibody response to mRNA vaccines was significantly found in LTX recipients compared to controls and was associated with the plasma concentration of mycophenolate. While repeating mRNA vaccination may be one of the strategies to improve antibody response given the safety of the vaccines, emerging data on humoral immune responses based on immunosuppression regimens in LTX recipients should be studied (jRCT1021210009).     

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.     

Adverse reactions to the BNT162b2 and mRNA-1273 mRNA COVID-19 vaccines in Japan

IntroductionThe BNT162b2 and mRNA-1273 COVID-19 vaccines are the main vaccines that have been used for mass vaccination in Japan. Information on adverse reactions to COVID-19 vaccines in the Japanese population is limited.MethodsWe conducted an online survey on self-reported adverse reactions in individuals who had received two doses of the BNT162b2 or mRNA-1273 vaccine. The incidence of adverse events after each dose of vaccine was investigated. Propensity score matching was used to compare the incidence of adverse reactions after the second dose of the BNT162b2 and mRNA-1273 vaccines.ResultsAfter the first and second doses of the BNT162b2 vaccine, and the first and second doses of the mRNA-1273 vaccine, 890, 853, 6401, and 3965 individuals, respectively, provided complete responses. Systemic reactions, including fever, fatigue, headache, muscle/joint pain, and nausea were significantly more common in females, individuals aged <50 years, and after the second dose. The incidence of injection site pain did not differ significantly according to the dose. The incidence of delayed injection site reactions after the first dose of mRNA-1273 vaccine was 3.9% and 0.8% among females and males, respectively, and 10.6% among females aged 40–69 years. Local and systemic reactions after the second dose, including fever, fatigue, headache, muscle/joint pain, nausea, and skin rash were more common in individuals who had received the mRNA-1273 vaccine.ConclusionsAdverse reactions were more frequently reported in females, younger individuals, and after the mRNA-1273 vaccine.     

Factors affecting the serologic response to SARS-CoV-2 vaccination in patients with solid tumors: A prospective study

ObjectiveTo evaluate the factors affecting seropositivity and antibody levels after SARS-CoV-2 vaccines in patients with cancer because they were excluded from clinical studies of SARS-CoV-2 vaccines.MethodsThis prospective, observational, single-center study included 290 patients with solid tumors followed up in our medical oncology clinic between March 2021 and August 2021. SARS-CoV-2 antibody status was determined before the first dose of vaccine. Fifty-one patients with positive prevaccine baseline antibody tests were excluded from the study, regardless of whether they had previously confirmed SARS-CoV-2 PCR positivity. To determine the quantitative IgG antibody response of the vaccines, blood samples were collected at least 28 days after each dose of vaccine. Quantitative IgG levels against virus spike protein receptor binding domain (RBD) were measured using chemiluminescent enzyme immunoassay (CLIA). Demographic and clinical features affecting seropositivity were analyzed.ResultsOne hundred and fifty-one (69.3%) patients were vaccinated with two doses of CoronaVac followed by one dose of BNT162b2 (Biontech) (group 1). Sixty-seven (30.7%) patients were vaccinated with three doses of BNT162b2 (group 2). The proportion of patients who developed seropositivity was significantly higher in group 2 (78.6% vs. 54.9%, p < 0.012). Antibody response increased significantly after the second dose of vaccine in both groups. Female sex, being younger than 65 years, and chemotherapy status were significantly related to higher anti-SARS-CoV-2 S antibody levels (p = 0.033, p = 0.036, and p = 0.047, respectively). Antibody levels were significantly higher in patients who had previously received chemotherapy than in patients receiving active chemotherapy (p = 0.042).ConclusionsOur study is the first to evaluate basal SARS-CoV-2 IgG levels before the first dose of vaccine and after three doses in patients with solid tumors. The rate of development of seropositivity with two doses of mRNA vaccine was found to be higher than with two doses of inactivated SARS-CoV-2 vaccine. More attention should be paid to preventive measures in addition to vaccination in patients aged over 65 years and men with cancer diagnoses.     

Reactogenicity following two doses of the BNT162b2 mRNA COVID-19 vaccine: Real-world evidence from healthcare workers in Japan

As the first authorized COVID-19 vaccine in Japan, the BNT162b2 mRNA COVID-19 vaccine is utilized for mass vaccination. Although efficacy has been proved, real-world evidence on reactogenicity in Japanese personnel is needed to prepare the public. Healthcare workers in a large academic hospital in Japan received two doses of the Pfizer-BioNTech vaccine from March 17 to May 19, 2021. Online questionnaires were distributed to registered recipients following each dose, from day 0 through day 8. Primary outcomes are the frequency of reactogenicity including local and systemic reactions. Length of absence from work was also analyzed. Most recipients self-reported reactogenicity after the first dose (97.3%; n = 3254; mean age [36.4]) and after the second dose (97.2%; n = 3165; mean age [36.5]). Systemic reactions following the second dose were substantially higher than the first dose, especially for fever (OR, 27.38; 95% CI, [22.00–34.06]; p < 0.001), chills (OR, 16.49; 95% CI, [13.53–20.11]; p < 0.001), joint pain (OR, 8.49; 95% CI, [7.21–9.99]; p < 0.001), fatigue (OR, 7.18; 95% CI, [6.43–8.02]; p < 0.001) and headache (OR, 5.43; 95% CI, [4.80–6.14]; p < 0.001). Reactogenicity was more commonly seen in young, female groups. 19.3% of participants took days off from work after the second dose (2.2% after the first dose), with 4.7% absent for more than two days. Although most participants reported reactogenicity, severe cases were limited. This study provides real-world evidence for the general population and organizations to prepare for BNT162b2 mRNA COVID-19 vaccination in Japan and other countries in the region.     

Factors associated with anti-SARS-CoV-2 IgG antibody production in patients convalescing from COVID-19

IntroductionAmong patients with coronavirus disease 2019 (COVID-19), the factors that affect anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody production remain unclear. This study aimed to identify such factors among patients convalescing from COVID-19.MethodsThis study comprised patients who had been diagnosed with COVID-19 between January 1 and June 30, 2020 and gave consent for anti-SARS-CoV-2 spike protein antibody measurement using enzyme-linked immunosorbent assay during their acute and/or convalescent phases. Factors related to elevated antibody titers and the relationship between the days from disease onset and the development of antibody titers were assessed.ResultsA total of 84 participants enrolled in the study. Nineteen participants had antibody titers measured during the convalescent phase only, and 65 participants had antibody titers measured during the acute and convalescent phases. The antibody titers peaked in weeks 5 and 6. The stepwise multivariate log-normal analysis revealed that male sex (P = 0.04), diabetes mellitus (P = 0.03), and high C-reactive protein levels during the disease course (P < 0.001) were associated with elevated IgG antibodies. Glucocorticoid use was not associated with antibody titers.ConclusionThe study found that high values of maximum CRP levels during the acute phase, male sex, and diabetes mellitus were associated with elevated antibody titers. Antibody titers tended to be highest in the first 5 or 6 weeks after the onset of symptoms.     

Humoral response and safety of the BNT162b2 and mRNA-1273 COVID-19 vaccines in allogeneic hematopoietic stem cell transplant recipients: An observational study

BackgroundThe effectiveness of mRNA COVID-19 vaccines and the optimal timing of vaccine administration in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) recipients remains inadequately investigated. We examine the effectiveness and safety of mRNA COVID-19 vaccines in allo-HSCT recipients.MethodThis prospective observational study included 44 allo-HSCT recipients and 38 healthy volunteers. The proportion of subjects acquiring anti-S1 IgG antibodies were considered as the primary endpoint. The occurrence of adverse events after vaccination and objective deterioration of chronic graft-versus-host disease (GVHD) were defined as secondary endpoints. In addition, we compared the geometric mean titers (GMT) of anti-S1 antibody titers in subgroups based on time interval between transplantation and vaccination.ResultsA humoral response to the vaccine was evident in 40 (91%) patients and all 38 healthy controls. The GMT of anti-S1 titers in patients and healthy controls were 277 (95% confidence interval [CI]: 120–643) BAU/mL and 532 (95% CI 400–708) BAU/mL, respectively. (p = 0.603). A short time interval between transplantation and vaccination (≤6 months) was associated with low anti-S1 IgG antibody titers. No serious adverse events and deterioration of chronic GVHD were observed. Only one case of new development of mild chronic GVHD was recorded.ConclusionMessenger RNA COVID-19 vaccines induce humoral responses in allo-HSCT recipients and can be administered safely.     

Effectiveness of the third dose of BNT162b2 vaccine on neutralizing Omicron variant in the Japanese population

IntroductionThe vaccine against SARS-CoV-2 provides humoral immunity to fight COVID-19; however, the acquired immunity gradually declines. Booster vaccination restores reduced humoral immunity; however, its effect on newly emerging variants, such as the Omicron variant, is a concern. As the waves of COVID-19 cases and vaccine programs differ between countries, it is necessary to know the domestic effect of the booster.MethodsSerum samples were obtained from healthcare workers (20–69 years old) in the Pfizer BNT162b2 vaccine program at the Toyama University Hospital 6 months after the second dose (6mA2D, n = 648) and 2 weeks after the third dose (2wA3D, n = 565). The anti-SARS-CoV-2 antibody level was measured, and neutralization against the wild-type and variants (Delta and Omicron) was evaluated using pseudotyped viruses. Data on booster-related events were collected using questionnaires.ResultsThe median anti-SARS-CoV-2 antibody was >30.9-fold elevated after the booster (6mA2D, 710.0 U/mL [interquartile range (IQR): 443.0–1068.0 U/mL]; 2wA3D, 21927 U/mL [IQR: 15321.0–>25000.0 U/mL]). Median neutralizing activity using 100-fold sera against wild-type-, Delta-, and Omicron-derived variants was elevated from 84.6%, 36.2%, and 31.2% at 6mA2D to >99.9%, 99.1%, and 94.6% at 2wA3D, respectively. The anti-SARS-CoV-2 antibody levels were significantly elevated in individuals with fever ≥37.5 °C, general fatigue, and myalgia, local swelling, and local hardness.ConclusionThe booster effect, especially against the Omicron variant, was observed in the Japanese population. These findings contribute to the precise understanding of the efficacy and side effects of the booster and the promotion of vaccine campaigns.     

Antibody titers against the Alpha,Beta, Gamma,and Delta variants of SARS-CoV-2 induced by BNT162b2 vaccination measured using automated chemiluminescent enzyme immunoassay

BackgroundLevels of 50% neutralizing titer (NT50) reflect the a vaccine-induced humoral immunity after the vaccination against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Measurements of NT50 are difficult to implement in large quantities. A high-throughput laboratory test is expected for determining the level of herd immunity against SARS-CoV-2.MethodsWe analyzed samples from 168 Japanese healthcare workers who had completed two doses of the BNT162b2 vaccine. We analyzed immunoglobulin G (IgG) index values against spike protein (SP) using automated chemiluminescent enzyme immunoassay system AIA-CL and analyzed the background factors affecting antibody titer. SP IgG index was compared with 50% neutralization titers.ResultsThe median SP IgG index values of the subjects (mean age = 43 years; 75% female) were 0.1, 1.35, 60.80, and 97.35 before and at 2, 4, and 6 weeks after the first dose, respectively. At 4 and 6 weeks after the first dose, SP IgG titers were found to have positive correlation with NT50 titer (r = 0.7535 in 4 weeks; r = 0.4376 in 6 weeks). Proportions of the SP IgG index values against the Alpha, Beta, Gamma, and Delta variants compared with the original strain were 2.029, 0.544, 1.017, and 0.6096 respectively. Older age was associated with lower SP IgG titer index 6 weeks after the first dose.ConclusionsSP IgG index values were rised at 3 weeks after two doses of BNT162b2 vaccination and have positive correlation with NT50. SP IgG index values were lower in the older individuals and against Beta and Delta strain.     

Correlates of SARS-CoV-2 anti-RBD IgG antibody titers among persons experiencing homelessness in Los Angeles

Objectives

People experiencing homelessness (PEH) have been especially impacted by the COVID-19 pandemic, likely due to increased vulnerabilities stemming from chronic diseases, substance use, and mental health conditions.

Design

A case–control study to assess the presence of antibodies against SARS-CoV-2 among PEH and associations with key variables.

Sample

A convenience sample of 97 PEH in Skid Row, Los Angeles.

Measurements

A structured questionnaire assessing socio-demographic, mental health, drug and alcohol use, health care access, pandemic stress, and other COVID-19-specific questions.

Results

We found high anti-receptor binding domain (RBD) IgG titers among five of 15 PEH who reported no prior COVID-19 diagnosis or being vaccinated, suggesting undiagnosed and/or asymptomatic COVID-19. While anti-RBD IgG titers across vaccination categories were not statistically significant (p = .069), participants vaccinated with Janssen had the lowest mean anti-RBD IgG titers. In multivariable analysis, we found negative associations between level of SARS-CoV-2 antibody titers with the Janssen vaccine and depression; thus, a need for integrated care for PEH with depression and COVID-19.

Conclusions

Further research is warranted to confirm the immune response, initial and over time, to SARS-CoV-2 infection and to COVID-19 vaccinations, particularly among PEH whose immune systems may be impacted by multiple health conditions.