Comparison of CLEIA and ELISA for SARS-CoV-2 Virus Antibodies after First and Second Dose Vaccinations with the BNT162b2 mRNA Vaccine.

The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has required rapid action to control its spread and vaccines are a fundamental solution to this pandemic. The development of rapid and reliable serological tests to monitor the antibody response to coronavirus disease vaccines is necessary for post-vaccination immune responses. Therefore, in this study, anti-SARS-CoV-2 antibody titers after the first and second doses were monitored using two different measurement systems, a highly sensitive analytical platform of chemiluminescent enzyme immunoassay (CLEIA) and an enzyme-linked immunosorbent assay (ELISA). Our study included 121 participants who received two doses of the BNT162b2 vaccine. Both methods show significant increase in anti-spike protein IgG antibody levels one week after the first vaccination, and then reached at a plateau at week five (week two after the second dose), with a 3.8 × 103-fold rise in CLEIA and a 22-fold rise in ELISA. CLEIA and ELISA showed a good correlation in the high titer range, >10 binding antibody unit (BAU)/mL. Both methods detected higher IgG antibody levels in females compared with male participants after the second vaccination, while CLEIA exhibits the sex difference after the first dose. Thus, our study showed better performance of CLEIA over ELISA in sensitivity, especially in the low concentration range, however ELISA was also useful in the high titer range (>10 BAU/mL) corresponding to the level seen several weeks after the first vaccination.

Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study.

This study assessed the immunogenicity and safety of the BNT162b2 mRNA vaccine in lung cancer patients receiving anticancer treatment. We enrolled lung cancer patients receiving anticancer treatment and non-cancer patients; all participants were fully vaccinated with the BNT162b2 vaccine. Blood samples were collected before the first and second vaccinations and 4 ± 1 weeks after the second vaccination. Anti-severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein S1 subunit receptor-binding domain antibody titers were measured using the Architect SARS-CoV-2 IgG II Quant and Elecsys Anti-SARS-CoV-2 S assays. Fifty-five lung cancer patients and 38 non-cancer patients were included in the immunogenicity analysis. Lung cancer patients showed significant increase in the geometric mean antibody concentration, which was significantly lower than that in the non-cancer patients after the first (30 vs. 121 AU/mL, p < .001 on Architect; 4.0 vs 1.2 U/mL, p < .001 on Elecsys) and second vaccinations (1632 vs. 3472 AU/mL, p = .005 on Architect; 213 vs 573 A/mL, p = .002 on Elecsys). The adjusted odds ratio (aOR) for seroprotection was significantly lower (p < .05) in lung cancer patients than that in non-cancer patients. Analysis of the anticancer treatment types showed that the aOR for seroprotection was significantly lower (p < .05) in lung cancer patients receiving cytotoxic agents. They showed no increase in adverse reactions. BNT162b2 vaccination in lung cancer patients undergoing anticancer treatment significantly increased (p < .05) antibody titers and showed acceptable safety. Immunogenicity in these patients could be inadequate compared with that in non-cancer patients.

Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan.

BACKGROUND: Although several assays are used to measure anti-receptor-binding domain (RBD) antibodies induced after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, the assays are not fully comparable in practice. This study evaluated the immunogenicity of the BNT162b2 mRNA vaccine in healthy adults using two immunoassays. METHODS: This prospective cohort study included SARS-CoV-2-naïve adults, predominantly healthcare workers, aged 20-64 years, who received two BNT162b2 vaccine doses between March and May 2021. Blood samples were collected before the first vaccination (S0), before the second vaccination (S1), 4 weeks after the second vaccination (S2), and 6 months after the second vaccination (S3). anti-RBD antibodies were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys anti-SARS-CoV-2 S (Roche Diagnostics) assays. RESULTS: Among the 385 participants, the geometric mean antibody titers (GMTs) on the Architect assay (AU/mL) were 7.5, 693, 7007, and 1030 for S0, S1, S2, and S3, respectively. The corresponding GMTs on the Elecsys assay (U/mL) were 0.40, 24, 928, and 659, respectively. The GMT ratio (S3/S2) was 0.15 on the Architect and 0.71 on the Elecsys assay. The correlation between antibody titers measured with the two assays were strong at all time points after vaccination (Spearman's correlation coefficient: 0.74 to 0.86, P < 0.01 for all). GMT was significantly lower in the older age group after vaccination (P < 0.01), with no significant differences according to sex. Seroprotection (≥5458 AU/mL on the Architect assay and ≥ 753 U/mL on the Elecsys) at each time point was 0 %, 1 %, 67 %, and 1 % on the Architect assay and 0 %, 1 %, 62 %, and 43 % on the Elecsys, respectively. CONCLUSIONS: Two BNT162b2 vaccine doses resulted in adequate anti-RBD antibody response, which varied by age. As the two assays showed different kinetics, the results of single immunoassays should be interpreted with caution.

Real-World Effectiveness of the mRNA COVID-19 Vaccines in Japan: A Case-Control Study.

The real-world effectiveness of the coronavirus disease 2019 (COVID-19) vaccines in Japan remains unclear. This case-control study evaluated the vaccine effectiveness (VE) of two doses of mRNA vaccine, BNT162b2 or mRNA-1273, against the delta (B.1.617.2) variant in the Japanese general population in the period June-September 2021. Individuals in close contact with COVID-19 patients were tested using polymerase chain reaction (PCR). A self-administered questionnaire evaluated vaccination status, demographic data, underlying medical conditions, lifestyle, personal protective health behaviors, and living environment. Two vaccine doses were reported by 11.6% of cases (n = 389) and 35.2% of controls (n = 179). Compared with controls, cases were younger and had a lower proportion who always performed handwashing for ≥20 s, a higher proportion of alcohol consumers, and a lower proportion of individuals living in single-family homes or with commuting family members. After adjusting for these confounding factors and day of PCR testing by multivariate logistic regression analysis, the VE in the period June-July (delta variant proportion 45%) was 92% and 79% in the period August-September (delta variant proportion 89%). The adjusted VE for homestay, hotel-based isolation and quarantine, and hospitalization was 78%, 77%, and 97%, respectively. Despite declining slightly, VE against hospitalization remained robust for ~3 months after the second dose. Vaccination policymaking will require longer-term monitoring of VE against new variants.

Acceptance of Booster COVID-19 Vaccine and Its Association with Components of Vaccination Readiness in the General Population: A Cross-Sectional Survey for Starting Booster Dose in Japan.

The Japanese government approved COVID-19 vaccine booster doses in November 2021. However, intentions and readiness for booster vaccines among the general population were unknown. This survey measured the intentions for COVID-19 booster vaccination. Among 6172 participants (53.2% female), 4832 (78.3%) accepted booster doses; 415 (6.7%) hesitated. Vaccination intention was associated with higher age, marital status, having children, underlying diseases, and social norms. To evaluate the readiness for vaccination, the seven component (7C) vaccination readiness scale was employed, comprising "Confidence", "Complacency", "Constraints", "Calculation", "Collective responsibility", "Compliance", and "Conspiracy". Participants with acceptance showed significantly higher 7C scores (p < 0.001) than those who hesitated or were unsure. Multivariable logistic regression analysis revealed that the "social norms" predictor was the strongest predictor of acceptance (adjusted odds ratio (AOR) 4.02, 95% confidence interval (CI): 3.64-4.45). "Constraints" (AOR: 2.27, 95% CI: 2.11-2.45) and "complacency" (AOR: 2.18, 95% CI: 2.03-2.34) were also strongly associated with acceptance, but "compliance" (AOR: 1.24, 95% CI: 1.18-1.31) and "conspiracy" (AOR: 1.42, 95% CI: 1.33-1.52) were weakly associated. The "7C vaccination readiness scale" is useful for measuring vaccine acceptance in the Japanese population. However, "social norms" might be more suitable than "compliance" and "conspiracy" for measuring vaccine acceptance in Japan.

Variant Allele of ALDH2, rs671, Associates with Attenuated Post-Vaccination Response in Anti-SARS-CoV-2 Spike Protein IgG: A Prospective Study in the Japanese General Population.

Uncovering the predictors of vaccine immunogenicity is essential for infection control. We have reported that the most prevalent polymorphism of the aldehyde dehydrogenase 2 gene (ALDH2), rs671, may be associated with an attenuated immune system. To test the inverse relationship between rs671 and antibody production after COVID-19 vaccination, the levels of anti-SARS-CoV-2 Spike protein S1 subunit (S1) IgG were repeatedly measured for four months before and after vaccination with BNT162b2 or mRNA-1273, in 88 Japanese workers and students (including 45 females, aged 21-56 years, with an rs671 variant allele frequency of 0.3). The mixed model including fixed effects of the vaccine type, weeks post vaccination (categorical variable), sex, age, height, smoking status, ethanol intake, exercise habit, perceived stress, steroid use, allergic diseases, and dyslipidemia, indicated an inverse association between log-transformed anti-S1 IgG levels and the number of rs671 variant alleles (partial regression coefficient = -0.15, p = 0.002). Our study indicated for the first time that the variant allele of ALDH2, rs671, is associated with the attenuated immunogenicity of COVID-19 mRNA vaccines. Our finding may provide a basis for personalized disease prevention based on a genetic polymorphism that is prevalent among East Asians.

Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study (preprint)

Introduction: This study assessed the immunogenicity and safety of BNT162b2 mRNA vaccine in lung cancer patients receiving anticancer treatment using two immunoassays. Methods: We enrolled lung cancer patients receiving anticancer treatment and non-cancer patients with chronic diseases; all participants were fully vaccinated with the BNT162b2 vaccine. Blood samples were collected before the first and second vaccinations and 4 {+/-} 1 weeks after the second vaccination. Anti-acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein S1 subunit receptor-binding domain antibody titers were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys Anti-SARS-CoV-2 S (Roche Diagnostics). Results: Fifty-five lung cancer patients and 38 non-cancer patients were included in the immunogenicity analysis. Lung cancer patients showed significant increase in the geometric mean antibody titer, which was significantly lower than that in the non-cancer patients after the first (30 vs. 121 AU/mL, p<0.001 on Architect; 4.0 vs 1.2 U/mL, p<0.001, on Elecsys) and second vaccinations (1632 vs. 3472 AU/mL, p=0.005, on Architect; 213 vs 573 A/mL, p=0.002, on Elecsys). The adjusted odds ratio (OR) for seroprotection was significantly lower in the lung cancer patients. Analysis of the anticancer treatment types showed that the adjusted OR for seroprotection was significantly lower in lung cancer patients receiving cytotoxic agents. Lung cancer patients showed no increase in the number of adverse reactions. Conclusions: BNT162b2 vaccination in lung cancer patients undergoing anticancer treatment significantly increased antibody titers and showed acceptable safety. However, the immunogenicity in these patients could be inadequate compared with that in non-cancer patients.

Comparison of CLEIA and ELISA for SARS-CoV-2 Virus Antibodies after First and Second Dose Vaccinations with the BNT162b2 mRNA Vaccine

The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has required rapid action to control its spread and vaccines are a fundamental solution to this pandemic. The development of rapid and reliable serological tests to monitor the antibody response to coronavirus disease vaccines is necessary for post-vaccination immune responses. Therefore, in this study, anti-SARS-CoV-2 antibody titers after the first and second doses were monitored using two different measurement systems, a highly sensitive analytical platform of chemiluminescent enzyme immunoassay (CLEIA) and an enzyme-linked immunosorbent assay (ELISA). Our study included 121 participants who received two doses of the BNT162b2 vaccine. Both methods show significant increase in anti-spike protein IgG antibody levels one week after the first vaccination, and then reached at a plateau at week five (week two after the second dose), with a 3.8 ×103-fold rise in CLEIA and a 22-fold rise in ELISA. CLEIA and ELISA showed a good correlation in the high titer range, >10 binding antibody unit (BAU)/mL. Both methods detected higher IgG antibody levels in females compared with male participants after the second vaccination, while CLEIA exhibits the sex difference after the first dose. Thus, our study showed better performance of CLEIA over ELISA in sensitivity, especially in the low concentration range, however ELISA was also useful in the high titer range (>10 BAU/mL) corresponding to the level seen several weeks after the first vaccination.

Association of Vaccine Confidence and Hesitancy in Three Phases of COVID-19 Vaccine Approval and Introduction in Japan.

Understanding vaccine hesitancy, considering the target region and phase, is an urgent issue to quell the coronavirus disease (COVID-19) pandemic. This study aimed to monitor COVID-19 vaccine hesitancy in the Japanese population during the three phases of vaccine approval and introduction, and evaluate the association of vaccine hesitancy with vaccine confidence and literacy. We conducted web-based cross-sectional surveys during the three phases of COVID-19 vaccine introduction: January 2021, before approval; June, start of vaccination of the elderly; and September, when about 70% of the target population was vaccinated with at least one dose. There were 7210 participants, aged 20-80 years. We evaluated the association of vaccine hesitancy with vaccine confidence and literacy in the three phases using multivariate logistic regression analysis. The proportion of hesitancy in January, June, and September was 17.5%, 65.3%, and 19.4%, respectively. In any phase, lower vaccine confidence and literacy showed a higher adjusted odds ratio (AOR) of vaccine hesitancy in most items (AOR > 1, p < 0.001). Vaccine hesitancy in June had a different trend in perception of COVID-19 compared to that in the January and September surveys. The findings suggested that hesitancy increases transiently during vaccination introduction phases, and changes as the vaccination program progressed or waves of epidemic. Careful risk communication to increase vaccine confidence and literacy is essential to reduce vaccine hesitancy, especially in the introduction phase.

Differences in COVID-19 Vaccine Acceptance, Hesitancy, and Confidence between Healthcare Workers and the General Population in Japan.

Little is known about the differences in coronavirus disease (COVID-19) vaccine acceptance and hesitancy between the general population and healthcare workers in Japan. To compare these differences, a nationwide web-based cross-sectional survey was conducted on 19 January 2021, shortly before the initiation of COVID-19 vaccinations in Japan. A total of 6180 men and women aged 20-69 years and 1030 healthcare workers aged 20-69 years were enrolled. Data on COVID-19 vaccine acceptance, basic characteristics, including socioeconomic factors, and confidence in immunization in general were collected. COVID-19 vaccine acceptance was also evaluated under hypothetical vaccine effectiveness and adverse event frequencies. Factors associated with vaccine hesitancy were examined using multinomial logistic regression analysis. The COVID-19 vaccine acceptance rate was 48.6% among the general population and was lower among nurses (45.5%) and medical clerks (40.7%). Women and young adults had significantly higher COVID-19 vaccine hesitancy odds ratios, and current smokers had significantly lower odds ratios. The frequency of adverse events was a COVID-19 vaccine hesitancy factor. Even if these factors were adjusted, COVID-19 vaccine hesitancy among nurses was 1.4 times higher than that among the general population. Thus, interventions to improve health literacy and vaccine hesitancy among the general population and healthcare workers, especially nurses, are needed.