Dynamics of Antibody Response to Covishield Vaccine after 6 Months: A Longitudinal Prospective Study.

To study the dynamics of antibody responses in the real world up to 6 months following two Covishield vaccination doses and evaluate its correlation with age. From March 2021 to February 2022, a prospective, longitudinal study of healthcare workers (HCWs) from a dedicated COVID-19 hospital was conducted. Institutional Ethics Committee permission was obtained. HCWs were divided into two groups. The first group consisted of individuals who had received the first dose of the COVID-19 vaccine, with at least 3 weeks elapsed since the dose, and who had not received the second dose until the initial blood sample for antibody testing was obtained. The second group consisted of individuals who had received both COVID-19 doses and had at least 2 weeks between the administration of the second dose and the collection of the first sample for antibody testing. In March 2021, after undergoing phlebotomy for serum collection, the participants responded to the survey. Electrochemiluminescence immunoassay (ECLIA) was used to perform a quantitative test for antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein receptor domain [receptor binding domain (RBD)]. The test used had a 98.8% sensitivity and a 99.9% specificity. If the antibody titer was 0.80 U/mL or higher, it was deemed positive; if it was lower, it was deemed negative. Two follow-ups were conducted for both groups, 3 and 6 months following the first sample collection. During both follow-up visits, a blood sample was obtained for testing the amount of antibody response, and the history of COVID-19 disease following the initial sample was taken. Every HCW had received the Covishield vaccination. After the vaccine's first dosage, 61 HCWs in the first group underwent antibody testing. The information about the 43 HCWs in the first group who attended the two follow-ups is as follows. There were 14 (32.6%) nurses and 5 (11.6%) doctors among the 43 HCWs. The age range was 21-55 years, with the median [interquartile range (IQR)] age being 26 (22-40) years and 20 (60.5%) being females. The vaccination series had a median (IQR) of 34 (29-49) days between doses. There was a statistically significant difference in immunoglobulin G (IgG) levels of the three samples, χ2 = 13.579, p = 0.001. Median (IQR) IgG levels of the three samples at 1 month after the first dose, 3 and 6 months after the second dose were 8511 (51-15400) U/mL, 1471 (249-5050) U/mL, and 978 (220-2854) U/mL, respectively. The antibody titer was negative for two HCWs in the first sample, positive in the rest of the samples, and positive in all samples in both follow-ups. In the second group, following two COVID-19 dosages, a total of 65 HCWs had tested positive for antibodies. The information of the 56 HCWs in group II who attended both follow-ups is as follows. Of the 56 HCWs, 15 (26.8%) were doctors, 27 (48.2%) were nurses, and 14 (25%) were others. The age range was 20-64 years, with a median (IQR) of 29.5 (22-37.7) and 31 (55.3%) female participants. The vaccination series had a median (IQR) interval of 32 (29-35) days between doses. There was a statistically significant difference in IgG levels of the three samples, χ2 = 31.107, p < 0.0001. Median (IQR) IgG levels of the three samples at 20 days, 3.8 months, and 7 months after the second dose were 2377.5, 1345.5, and 1257 U/mL, respectively. Spearman's rank order correlation was used to assess the association between IgG level and age in both groups. The relationship between IgG levels and age was weakly correlated and not statistically significant. There is a waning of antibody titer over time postimmunization. A lower antibody titer can be a contributing factor for infections that emerge later. IgG levels postvaccination do not differ according to age.

Chavhan SS ，Dhikale PT ，Adsul BB ，Kinge KV ，Ingale AR ，Gokhale CN ，Jadhav N ... -  《-》

BNT162b2 COVID-19 vaccine and correlates of humoral immune responses and dynamics: a prospective, single-centre, longitudinal cohort study in health-care workers.

Concurrent with the Pfizer-BioNTech BNT162b2 COVID-19 vaccine roll-out in Israel initiated on Dec 19, 2020, we assessed the early antibody responses and antibody kinetics after each vaccine dose in health-care workers of different ages and sexes, and with different comorbidities. We did a prospective, single-centre, longitudinal cohort study at the Sheba Medical Centre (Tel-Hashomer, Israel). Eligible participants were health-care workers at the centre who had a negative anti-SARS-CoV-2 IgG assay before receiving the first dose of the intramuscular vaccine, and at least one serological antibody test after the first dose of the vaccine. Health-care workers with a positive SARS-CoV-2 PCR test before vaccination, a positive anti-SARS-CoV-2 IgG serology test before vaccination, or infection with COVID-19 after vaccination were excluded from the study. Participants were followed up weekly for 5 weeks after the first vaccine dose; a second dose was given at week 3. Serum samples were obtained at baseline and at each weekly follow-up, and antibodies were tested at 1-2 weeks after the first vaccine dose, at week 3 with the administration of the second vaccine dose, and at weeks 4-5 (ie, 1-2 weeks after the second vaccine dose). Participants with comorbidities were approached to participate in an enriched comorbidities subgroup, and at least two neutralising assays were done during the 5 weeks of follow-up in those individuals. IgG assays were done for the entire study population, whereas IgM, IgA, and neutralising antibody assays were done only in the enriched comorbidities subgroup. Concentrations of IgG greater than 0·62 sample-to-cutoff (s/co) ratio and of IgA greater than 1·1 s/co, and titres of neutralising antibodies greater than 10 were considered positive. Scatter plot and correlation analyses, logistic and linear regression analyses, and linear mixed models were used to investigate the longitudinal antibody responses. Between Dec 19, 2020, and Jan 30, 2021, we obtained 4026 serum samples from 2607 eligible, vaccinated participants. 342 individuals were included in the enriched comorbidities subgroup. The first vaccine dose elicited positive IgG and neutralising antibody responses at week 3 in 707 (88·0%) of 803 individuals, and 264 (71·0%) of 372 individuals, respectively, which were rapidly increased at week 4 (ie, 1 week after the second vaccine dose) in 1011 (98·4%) of 1027 and 357 (96·5%) of 370 individuals, respectively. Over 4 weeks of follow-up after vaccination, a high correlation (r=0·92) was detected between IgG against the receptor-binding domain and neutralising antibody titres. First-dose induced IgG response was significantly lower in individuals aged 66 years and older (ratio of means 0·25, 95% CI 0·19-0·31) and immunosuppressed individuals (0·21, 0·14-0·31) compared with individuals aged 18·00-45·99 years and individuals with no immunosuppression, respectively. This disparity was partly abrogated following the second dose. Overall, endpoint regression analysis showed that lower antibody concentrations were consistently associated with male sex (ratio of means 0·84, 95% CI 0·80-0·89), older age (ie, ≥66 years; 0·64, 0·58-0·71), immunosuppression (0·44, 0·33-0·58), and other specific comorbidities: diabetes (0·88, 0·79-0·98), hypertension (0·90, 0·82-0·98), heart disease (0·86, 0·75-1·00), and autoimmune diseases (0·82, 0·73-0·92). BNT162b2 vaccine induces a robust and rapid antibody response. The significant correlation between receptor-binding domain IgG antibodies and neutralisation titres suggests that IgG antibodies might serve as a correlate of neutralisation. The second vaccine dose is particularly important for older and immunosuppressed individuals, highlighting the need for timely second vaccinations and potentially a revaluation of the long gap between doses in some countries. Antibody responses were reduced in susceptible populations and therefore they might be more prone to breakthrough infections. Sheba Medical Center, Israel Ministry of Health.

Lustig Y ，Sapir E ，Regev-Yochay G ，Cohen C ，Fluss R ，Olmer L ，Indenbaum V ，Mandelboim M ，Doolman R ，Amit S ，Mendelson E ，Ziv A ，Huppert A ，Rubin C ，Freedman L ，Kreiss Y ... -  《-》

Healthcare Workers in South Korea Maintain a SARS-CoV-2 Antibody Response Six Months After Receiving a Second Dose of the BNT162b2 mRNA Vaccine.

Effective vaccines against coronavirus disease 2019 (COVID-19) are available worldwide; however, the longevity of vaccine effectiveness is not known. We performed a prospective observational study to assess the antibody response of healthcare workers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after BNT162b2 mRNA COVID-19 vaccination. SARS-CoV-2 neutralizing antibody (nAb) and spike (S) protein-IgG (S-IgG) antibody titers were examined in participants who received two doses of the BNT162b2 mRNA COVID-19 vaccine in a single center between March 1, 2021, and October 11, 2021. Antibody levels were analyzed at four times: before vaccination (visit 1), 4 weeks after the first vaccination (visit 2), 3 months after the second vaccination (visit 3), and 6 months after the second vaccination (visit 4). A total of 249 healthcare workers at Jeju National University Hospital were enrolled in this study, and 982 blood samples were analyzed. The mean age was 38.1 ± 9.5 years, and 145 (58.2%) participants were females. Positive nAbs (inhibition rates ≥ 20%) were measured in 166/249 (66.7%) subjects at visit 2, 237/243 (97.5%) subjects at visit 3, and 150/237 (63.3%) subjects at visit 4. A S-IgG (≥50 AU/mL) positivity was detected in 246/249 (98.8%) subjects at visit 1, and all participants had positive S-IgG antibody levels at visits 3 and 4 after being fully vaccinated. Further analysis of S-IgG levels revealed a median quantitative antibody level of 1275.1 AU/mL (interquartile range [IQR] 755.5-2119.0) at visit 2, 2765.9 AU/mL (IQR 1809.8-4138.4) at visit 3, and 970.1 AU/mL (IQR 606.0-1495.9) at visit 4. Patient characteristics, such as age, body mass index, and comorbidity, had no relationship with nAb or S-IgG levels at any of the visits. Considering the change in antibody levels over time, both nAb and S-IgG levels at visit 4 decreased compared with the corresponding levels at visit 3. No evidence of SARS-CoV-2 infection was found among any of the participants throughout the study. The BNT162b2 mRNA vaccine was effective in protecting healthcare personnel working in COVID-19-related departments. While the level of S-IgG antibodies was maintained for 6 months after the second vaccination, nAb levels waned over this 6-month period, indicating the need for a booster vaccination in some healthcare workers 6 months after full vaccination. Herein, we suggest that further studies are needed to evaluate the need for an interval of booster vaccination after full vaccination.

Choi JH ，Kim YR ，Heo ST ，Oh H ，Kim M ，Lee HR ，Yoo JR ... -  《Frontiers in Immunology》

[Antibody Response After Two Doses of Inactivated SARS-CoV-2 Vaccine in Healthcare Workers with and without Previous COVID-19 Infection: A Prospective Observational Study].

Özgür D ，Tütüncü EE 《MIKROBIYOLOJI BULTENI》

Real-world serological responses to extended-interval and heterologous COVID-19 mRNA vaccination in frail, older people (UNCoVER): an interim report from a prospective observational cohort study.

The use of COVID-19 vaccines has been prioritised to protect the most vulnerable-notably, older people. Because of fluctuations in vaccine availability, strategies such as delayed second dose and heterologous prime-boost have been used. However, the effectiveness of these strategies in frail, older people are unknown. We aimed to assess the antigenicity of mRNA-based COVID-19 vaccines in frail, older people in a real-world setting, with a rationed interval dosing of 16 weeks between the prime and boost doses. This prospective observational cohort study was done across 12 long-term care facilities of the Montréal Centre-Sud - Integrated University Health and Social Services Centre in Montréal, Québec, Canada. Under a rationing strategy mandated by the provincial government, adults aged 65 years and older residing in long-term care facilities in Québec, Canada, with or without previously documented SARS-CoV-2 infection, were administered homologous or heterologous mRNA vaccines, with an extended 16-week interval between doses. All older residents in participating long-term care facilities who received two vaccine doses were eligible for inclusion in this study. Participants were enrolled from Dec 31, 2020, to Feb 16, 2021, and data were collected up to June 9, 2021. Clinical data and blood samples were serially collected from participants at the following timepoints: at baseline, before the first dose; 4 weeks after the first dose; 6-10 weeks after the first dose; 16 weeks after the first dose, up to 2 days before administration of the second dose; and 4 weeks after the second dose. Sera were tested for SARS-CoV-2-specific IgG antibodies (to the trimeric spike protein, the receptor-binding domain [RBD] of the spike protein, and the nucleocapsid protein) by automated chemiluminescent ELISA. Two cohorts were used in this study: a discovery cohort, for which blood samples were collected before administration of the first vaccine dose and longitudinally thereafter; and a confirmatory cohort, for which blood samples were only collected from 4 weeks after the prime dose. Analyses were done in the discovery cohort, with validation in the confirmatory cohort, when applicable. The total study sample consisted of 185 participants. 65 participants received two doses of mRNA-1273 (Spikevax; Moderna), 36 received two doses of BNT162b2 (Comirnaty; Pfizer-BioNTech), and 84 received mRNA-1273 followed by BNT162b2. In the discovery cohort, after a significant increase in anti-RBD and anti-spike IgG concentrations 4 weeks after the prime dose (from 4·86 log binding antibody units [BAU]/mL to 8·53 log BAU/mL for anti-RBD IgG and from 5·21 log BAU/mL to 8·05 log BAU/mL for anti-spike IgG), there was a significant decline in anti-RBD and anti-spike IgG concentrations until the boost dose (7·10 log BAU/mL for anti-RBD IgG and 7·60 log BAU/mL for anti-spike IgG), followed by an increase 4 weeks later for both vaccines (9·58 log BAU/mL for anti-RBD IgG and 9·23 log BAU/mL for anti-spike IgG). SARS-CoV-2-naive individuals showed lower antibody responses than previously infected individuals at all timepoints tested up to 16 weeks after the prime dose, but achieved similar antibody responses to previously infected participants by 4 weeks after the second dose. Individuals primed with the BNT162b2 vaccine showed a larger decrease in mean anti-RBD and anti-spike IgG concentrations with a 16-week interval between doses (from 8·12 log BAU/mL to 4·25 log BAU/mL for anti-RBD IgG responses and from 8·18 log BAU/mL to 6·66 log BAU/mL for anti-spike IgG responses) than did those who received the mRNA-1273 vaccine (two doses of mRNA-1273: from 8·06 log BAU/mL to 7·49 log BAU/mL for anti-RBD IgG responses and from 6·82 log BAU/mL to 7·56 log BAU/mL for anti-spike IgG responses; mRNA-1273 followed by BNT162b2: from 8·83 log BAU/mL to 7·95 log BAU/mL for anti-RBD IgG responses and from 8·50 log BAU/mL to 7·97 log BAU/mL for anti-spike IgG responses). No differences in antibody responses 4 weeks after the second dose were noted between the two vaccines, in either homologous or heterologous combinations. Interim results of this ongoing longitudinal study show that among frail, older people, previous SARS-CoV-2 infection and the type of mRNA vaccine influenced antibody responses when used with a 16-week interval between doses. In these cohorts of frail, older individuals with a similar age and comorbidity distribution, we found that serological responses were similar and clinically equivalent between the discovery and confirmatory cohorts. Homologous and heterologous use of mRNA vaccines was not associated with significant differences in antibody responses 4 weeks following the second dose, supporting their interchangeability. Public Health Agency of Canada, Vaccine Surveillance Reference Group; and the COVID-19 Immunity Task Force. For the French translation of the abstract see Supplementary Materials section.

Vinh DC ，Gouin JP ，Cruz-Santiago D ，Canac-Marquis M ，Bernier S ，Bobeuf F ，Sengupta A ，Brassard JP ，Guerra A ，Dziarmaga R ，Perez A ，Sun Y ，Li Y ，Roussel L ，Langelier MJ ，Ke D ，Arnold C ，Whelan M ，Pelchat M ，Langlois MA ，Zhang X ，Mazer BD ，COVID-19 Immunity Task Force and UNCoVER Investigators ... -  《The Lancet Healthy Longevity》