Background Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear. Methods We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months. Results The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman’s rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46). Conclusions Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

Background Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. Methods At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case–control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. Results Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. Conclusions Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.

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Background 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. Methods 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. Findings 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. Thi...

Objectives The immunogenicity and safety of the Pfizer-BioNTech BNT162b2 mRNA vaccine in people living with HIV-1 (PLWH) are unknown. We thus aimed to assess the immunogenicity and safety of this vaccine in PLWH. Methods In this prospective open study, we enrolled 143 PLWH, aged ≥18 years, who attended our clinic and 261 immunocompetent health care workers (HCWs). SARS-CoV-2 receptor binding domain (RBD) IgG and neutralizing antibodies were measured. Adverse events, viral load and CD4 cell counts were monitored. Results At a median of 18 days (IQR 14-21) after the second dose, anti-RBD IgG was positive in 139/141 (98%) PLWH. Among HCWs, 258/261 (98.9%) developed anti-RBD IgG at a median of 26 (IQR 24-27) days after the second dose. Following the second dose, immune sera neutralized SARS-CoV-2 pseudo-virus in 97% and 98% of PLWH and HCW, respectively. Adverse events were reported in 60% of PLWH, mainly pain at the injection site, fatigue, and headache. AIDS-related adverse events were not reported. HIV viral load increased in 3/143 (2%) patients from < 40 copies/mL to ≤ 100 copies/mL. CD4+ T cell count decreased from a geometric mean of 700 (95% CI 648–757) cells per μL to 633.8 (95% CI 588–683) cells per μL (P<0.01). Conclusions BNT162b2 mRNA vaccine appears immunogenic and safe in PLWH who are on ART with unsuppressed CD4 count and suppressed viral load.

Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated in the oral cavity in response to COVID-19 vaccination. We collected serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines and measured the level of anti-SARS-CoV-2 Ab. We detected anti-Spike and anti-Receptor Binding Domain (RBD) IgG and IgA, as well as anti-Spike/RBD associated secretory component in the saliva of most participants after dose 1. Administration of a second dose of mRNA boosted the IgG but not the IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants exhibited diminished anti-Spike/RBD IgG levels, although secretory component-associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 variants had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2–4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection.

Background The exclusion of pregnant women from COVID-19 mRNA vaccine trials raised hesitancy regarding the benefit of vaccination of pregnant women, hence little is known about the vaccine's efficacy in this population. Objective To determine the maternal-neonatal transplacental transfer of SARS CoV-2 antibodies among vaccinated parturient women. A control group of COVID 19 recovered patients was included in order to compare IgG levels between vaccinated and recovered patients. Study Design A prospective cohort study in a single tertiary medical center in Israel between February and March 2021; parturient women who had been vaccinated with BNT162B2 mRNA vaccine during pregnancy were included and compared to COVID-19 recovered parturient women. SARS CoV-2 IgG antibodies were measured in maternal and cord sera, dried blood spot samples taken from newborns, and breast-milk samples. The primary outcome was to determine whether neonatal cord and dried blood spot samples were positive for SARS CoV-2 antibodies and to evaluate transfer ratio defined as cord blood IgG divided by maternal IgG levels. Results The study included 64 vaccinated parturient women and 11 parturient women who had COVID-19 disease during pregnancy. All maternal blood sera samples and 98.3% of cord blood sera samples were positive for SARS Cov-2 IgG with median concentrations of 26.1 (IQR 22.0;39.7) and 20.2 (IQR 12.7;29.0) respectively. Similarly, 96.4% of neonatal blood spot samples and all breast milk samples were positive for SARS CoV-2 IgG with median concentrations of 11.0 (IQR 7.2;12.8) and 4.9 (IQR 3.8;6.0), respectively. There was a significant positive correlation between maternal serum levels of SARS Cov-2 IgG and cord blood (R=0.483, p=0.0001), neonatal blood spot (R=0.515, p=0.004), and breast milk levels (R=0.396, p=0.005) of SARS CoV-2 IgG. The median placental transfer ratio of SARS-COV-2 IgG was 0.77. Comparison of vaccinated with recovered COVID-19 patients revealed significantly higher SARS CoV-2 IgG levels in maternal serum and cord blood among vaccinated women (p<0.0001). Conclusion(s) Our study demonstrated efficient transfer of SARS CoV-2 IgG across the placenta from women vaccinated with BNT162b2 mRNA vaccine during pregnancy to their neonates with positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity.