Antibody response induced by the BNT162b2 mRNA COVID-19 vaccine in a cohort of health-care workers,with or without prior SARS-CoV-2 infection: a prospective study

ObjectivesTo assess the antibody response to BNT162b2 mRNA COVID-19 vaccine in a cohort of health-care workers (HCW), comparing individuals with previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and SARS-CoV-2-naive individuals.MethodsHCW were tested at T0 (day of first dose), T1 (day of second dose) and T2 (2–3 weeks after second dose) for IgG anti-nucleocapsid protein, IgM anti-spike protein and IgG anti-receptor binding domain (IgG-RBD-S). The antibody response was compared between four main groups: group A, individuals with previous infection and positive antibodies at baseline; group B, individuals with the same history but negative antibodies; group C, individuals with no infection history but positive antibodies; group D, naive individuals. Repeated measures analysis was used to compare results over time-points.ResultsA total of 1935 HCW were included. Median IgG-RBD-S titre was significantly higher for group A (232 individuals) than for group B (56 individuals) both at T1 (A: 22 763 AU/mL, interquartile range (IQR) 14 222–37 204 AU/mL; B: 1373 AU/mL, IQR 783–3078 AU/mL, p 0.0003) and T2 (A: 30 765 AU/mL, IQR 19 841–42 813 AU/mL; B: 13 171 AU/mL, IQR 2324–22 688 AU/mL, p 0.0038) and for group D (1563 individuals; 796 AU/mL, IQR 379–1510 AU/mL at T1; 15 494 AU/mL, IQR 9122–23 916 AU/mL at T2, p < 0.0001 for both time-points). T1 values of group A were also significantly higher than T2 values of group D (p < 0.0001). Presence of symptoms, younger age and being female were associated with stronger antibody response. HCW infected in March showed a significantly stronger response (T1: 35 324 AU/mL, IQR 22 003–44 531 AU/mL; T2: 37 648 AU/mL, IQR 27 088–50 451 AU/mL) than those infected in November (T1: 18 499 AU/mL, IQR 11 492–27 283 AU/mL; T2: 23 210 AU/mL, IQR 18 074–36 086 AU/mL, p < 0.0001 for both time-points.ConclusionsIndividuals with past SARS-CoV-2 infection had a strong antibody response after one single vaccine shot. A single dose might be sufficient for this group, regardless of the time elapsed since infection; however, the clinical correlation with antibody response needs to be studied.     

Real-world safety data for the Pfizer BNT162b2 SARS-CoV-2 vaccine: historical cohort study

ObjectiveThe Pfizer BNT162b2 vaccine showed a reassuring safety profile in clinical trials, but real-world data are scarce. Bell's palsy, herpes zoster, Guillain–Barré syndrome (GBS) and other neurological complaints in proximity to vaccination have received special public attention. We compared their rates among vaccinated and unvaccinated individuals.MethodsIndividuals ≥16 years vaccinated with at least one dose of BNT162b2 were eligible for this historical cohort study in a health maintenance organization insuring 1.2 million citizens. Each vaccinee was matched to a non-vaccinated control by sex, age, population sector (general Jewish, Arab, ultra-orthodox Jewish) and comorbidities. Diagnosis of Covid-19 before or after vaccination was an exclusion criterion. The outcome was a diagnosis of Bell's palsy, GBS, herpes zoster or symptoms of numbness or tingling, coded in the visit diagnosis field using ICD-9 codes. Diagnoses of Bell's palsy and GBS were verified by individual file review.ResultsOf 406 148 individuals vaccinated during the study period, 394 609 (97.2%) were eligible (11 539 excluded). A total of 233 159 (59.1%) were matched with unvaccinated controls. Mean follow was 43 ± 15.14 days. In vaccinated and unvaccinated individuals there were 23 versus 24 cases of Bell's palsy (RR 0.96, CI 0.54–1.70), one versus zero cases of GBS, 151 versus 141 cases of herpes zoster (RR 1.07, CI 0.85–1.35) and 605 versus 497 cases of numbness or tingling (RR 1.22, CI 1.08–1.37), respectively.DiscussionNo association was found between vaccination, Bell's palsy, herpes zoster or GBS. Symptoms of numbness or tingling were more common among vaccinees. This study adds reassuring data regarding the safety of the BNT162b2 vaccine.     

Humoral serological response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation

ObjectivesTo assess the humoral immune response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation (HCT).MethodsThis is a prospective cohort study. The SARS-CoV-2 IgGII Quant (Abbott©) assay was performed 4–6 weeks after the second BNT162b2 vaccine for quantitative measurement of anti-spike antibodies.ResultsThe cohort included 106 adult patients. Median time from HCT to vaccination was 42 (range 4–439) months. Overall, 15/106 (14%, 95% confidence interval (CI) 7–21%) were seronegative despite vaccination, 14/52 patients on immunosuppression (27%, 95%CI 19–35%) compared to only 1/54 patients off immunosuppression (1.8%, 95%CI 1–4%) (p 0.0002). The proportion of seronegative patients declined with time; it was 46% (6/13) during the first year, 12.5% (3/24) during the second year and 9% (6/69) beyond 2 years from transplant. Patients with acute graft-versus-host disease (GVHD) (odds ratio (OR) 3.3, 95%CI 0.97–11.1, p 0.06) and moderate to severe chronic GVHD (OR 5.9, 95%CI 1.2–29, p 0.03) were more likely to remain seronegative. Vaccination was well tolerated by most patients. However, 7% (7/106) reported that GVHD-related symptoms worsened within days following vaccination.ConclusionA significant proportion of allogeneic HCT recipients receiving immunosuppression demonstrated an inadequate humoral response to the BNT162b2 vaccine. These patients should be recognized and instructed to take appropriate precautions. Recipients who were off immunosuppression had a humoral response that was comparable to that of the general population.     

Strong SARS-CoV-2 Antibody Response After Booster Dose of BNT162b2 mRNA Vaccines in Uninfected Healthcare Workers

Despite strict guidelines for coronavirus disease 2019 (COVID-19), South Korea is facing its fourth pandemic wave. In this study, by using an automated electrochemiluminescence immunoassay assay, we tracked anti-spike protein receptor-binding domain (anti-S-RBD) antibody titer from the second dose to 2 weeks after the booster dose vaccination. After the second dose, 234 participants had their anti-S-RBD antibody titers decrease over time. We also showed the booster dose (the third dose) increased antibody titer by average 14 (min–max, 2–255)-fold higher compared to the second dose among the 211-booster group participants, therefore, the booster dose could be recommended for low responders to the second dose. Our findings showed a distinct humoral response after booster doses of BNT162b2 mRNA vaccines and may provide further evidence of booster vaccination efficacy. These data will also be helpful in vaccination policy decisions that determine the need for the booster dose.     

Early antibody response in health-care professionals after two doses of SARS-CoV-2 mRNA vaccine (BNT162b2)

ObjectivesData on the immune response after two doses of BNT162b2 are so far limited. Previously infected individuals were excluded from pivotal clinical trials and the optimum dose regimen in this population has not been clearly studied. The CRO-VAX HCP study aims to investigate the early antibody response in a population of health-care professionals having received two doses of the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine.MethodsThe CRO-VAX HCP study is a multicentre, prospective, interventional study conducted in several sites in Belgium. The study included 231 health-care professional volunteers who received the two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine. Of these, 73 were previously infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 158 were uninfected and seronegative. In the first group, blood samples were collected at baseline and after 2, 4, 7, 10, 14, 21 and 28 days. In the second group, samples were obtained at baseline and after 14 and 28 days. Antibodies against the SARS-CoV-2 nucleocapsid and the receptor binding domain of the S1 subunit of the spike protein were measured in all individuals at different time-points.ResultsIn uninfected individuals, 95.5% (95% CI 91.0%–98.2%) developed anti-spike antibodies after 14 days and a 24.9-fold rise (95% CI 21.4%–28.9%) in antibody titre was observed after the second dose. In previously infected individuals, peak antibody response was reached after 7 days (i.e. 6347 U/mL) and the second dose did not lead to significantly higher antibody titres (i.e. 8856–11 911 U/mL). Antibody titres were higher in previously infected individuals.ConclusionsThis study supports the concept that a single dose of BNT162b2 would be sufficient in previously infected individuals.     

Antibody responses to BNT162b2 mRNA COVID-19 vaccine and their predictors among healthcare workers in a tertiary referral hospital in Japan

ObjectivesThis study aimed to determine antibody responses in healthcare workers who receive the BNT162b2 mRNA COVID-19 vaccine and identify factors that predict the response.MethodsWe recruited healthcare workers receiving the BNT162b2 mRNA COVID-19 vaccine at the Chiba University Hospital COVID-19 Vaccine Center. Blood samples were obtained before the 1st dose and after the 2nd dose vaccination, and serum antibody titers were determined using Elecsys® Anti-SARS-CoV-2S, an electrochemiluminescence immunoassay. We established a model to identify the baseline factors predicting post-vaccine antibody titers using univariate and multivariate linear regression analyses.ResultsTwo thousand fifteen individuals (median age 37-year-old, 64.3% female) were enrolled in this study, of which 10 had a history of COVID-19. Before vaccination, 21 participants (1.1%) had a detectable antibody titer (≥0.4 U/mL) with a median titer of 35.9 U/mL (interquartile range [IQR] 7.8 – 65.7). After vaccination, serum anti-SARS-CoV-2S antibodies (≥0.4 U/mL) were detected in all 1774 participants who received the 2nd dose with a median titer of 2060.0 U/mL (IQR 1250.0 – 2650.0). Immunosuppressive medication (p < 0.001), age (p < 0.001), time from 2nd dose to sample collection (p < 0.001), glucocorticoids (p = 0.020), and drinking alcohol (p = 0.037) were identified as factors predicting lower antibody titers after vaccination, whereas previous COVID-19 (p < 0.001), female (p < 0.001), time between 2 doses (p < 0.001), and medication for allergy (p = 0.024) were identified as factors predicting higher serum antibody titers.ConclusionsOur data demonstrate that healthcare workers universally have good antibody responses to the BNT162b2 mRNA COVID-19 vaccine. The predictive factors identified in our study may help optimize the vaccination strategy.     

SARS-CoV-2 new infections among health-care workers after the first dose of the BNT162b2 mRNA COVID-19 vaccine. A hospital-wide cohort study

ObjectivesTo evaluate the effect of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on the incidence of new SARS-CoV-2 infections in health-care workers (HCW).MethodsThe evolution of the incident rate of microbiologically confirmed SARS-CoV-2 infection in a cohort of 2590 HCW after BNT162b2 mRNA SARS-CoV-2 vaccination, compared with the rate in the community (n = 170 513) was evaluated by mixed Poisson regression models.ResultsA total of 1820 HCW (70.3% of total) received the first dose of the BNT162b2 mRNA vaccine between 10 January and 16 January 2021, and 296 (11.4%) received it the following week. All of them completed vaccination 3 weeks later. Incidence rates of SARS-CoV-2 infection after the first dose of mRNA SARS-CoV-2 vaccine declined by 71% (Incidence Rate Ratio (IRR) 0.286, 95% CI 0.174–0.468; p < 0.001) and by 97% (IRR 0.03, 95% CI 0.013–0.068; p < 0.001) after the second dose, compared with the perivaccine time. SARS-CoV-2 incidence rates in the community (with a negligible vaccination rate) had a much lower decline: 2% (IRR 0.984, 95% CI 0.943–1.028; p 0.47) and 61% (IRR 0.390, 95% CI 0.375–0.406; p < 0.001) for equivalent periods. Adjusting for the decline in the community, the reduction in the incident rates among HCW were 73% (IRR 0.272, 95% CI 0.164–0.451 p < 0.001) after the first dose of the vaccine and 92% (IRR 0.176, 95% CI 0.033–0.174; p < 0.001) after the second dose.ConclusionsmRNA SARS-CoV-2 vaccination is associated with a dramatic decline in new SARS-CoV-2 infection among HCW, even before the administration of the second dose of the vaccine.     

Vaccine-induced binding and neutralizing antibodies against Omicron 6 months after a homologous BNT162b2 booster

Evidence about the long-term persistence of the booster-mediated immunity against Omicron is mandatory for pandemic management and deployment of vaccination strategies. A total of 155 healthcare professionals (104 COVID-19 naive and 51 with a history of SARS-CoV-2 infection) received a homologous BNT162b2 booster. Binding antibodies against the spike protein and neutralizing antibodies against Omicron were measured at several time points before and up to 6 months after the booster. Geometric mean titers of measured antibodies were correlated to vaccine efficacy (VE) against symptomatic disease. Compared to the highest response, a significant 10.2- and 11.5-fold decrease in neutralizing titers was observed after 6 months in participants with and without history of SARS-CoV-2 infection. A corresponding 2.5- and 2.9-fold decrease in binding antibodies was observed. The estimated T_1/2 of neutralizing antibodies in participants with and without history of SARS-CoV-2 infection was 42 (95% confidence interval [CI]: 25–137) and 36 days (95% CI: 25–65). Estimated T_1/2 were longer for binding antibodies: 168 (95% CI: 116–303) and 139 days (95% CI: 113–180), respectively. Both binding and neutralizing antibodies were strongly correlated to VE (r = 0.83 and 0.89). However, binding and neutralizing antibodies were modestly correlated, and a high proportion of subjects (36.7%) with high binding antibody titers (i.e., >8434 BAU/ml) did not have neutralizing activity. A considerable decay of the humoral response was observed 6 months after the booster, and was strongly correlated with VE. Our study also shows that commercial assays available in clinical laboratories might require adaptation to better predict neutralization in the Omicron era.     

Omicron-specific mRNA vaccine induced cross-protective immunity against ancestral SARS-CoV-2 infection with low neutralizing antibodies

The major challenge in COVID-19 vaccine effectiveness is immune escape by SARS-CoV-2 variants. To overcome this, an Omicron-specific messenger RNA (mRNA) vaccine was designed. The extracellular domain of the spike of the Omicron variant was fused with a modified GCN4 trimerization domain with low immunogenicity (TSomi). After immunization with TSomi mRNA in hamsters, animals were challenged with SARS-CoV-2 virus. The raised nonneutralizing antibodies or cytokine secretion responses can recognize both Wuhan S and Omicron S. However, the raised antibodies neutralized SARS-CoV-2 Omicron virus infection but failed to generate Wuhan virus neutralizing antibodies. Surprisingly, TSomi mRNA immunization protected animals from Wuhan virus challenge. These data indicated that non-neutralizing antibodies or cellular immunity may play a more important role in vaccine-induced protection than previously believed. Next-generation COVID-19 vaccines using the Omicron S antigen may provide sufficient protection against ancestral or current SARS-CoV-2 variants.     

Durability of humoral and cell-mediated immune response after SARS-CoV-2 mRNA vaccine administration

Vaccination against the SARS-Cov-2 virus is an effective way to protect against the disease and the severe course of COVID-19. Forty-nine fully vaccinated with mRNA vaccines (BNT162b2 or mRNA-1273) SARS-CoV-2 infection-naïve volunteers aged 33–89 were enrolled in the study. Evaluation of the cellular and humoral immune response was performed within 1 to 3 months (T1) and 6–9 months (T2) after the second injection, and within 2–3 months (T3) after a booster dose. Additionally, a comparative analysis of the specific immune status was made between two age groups—below 60 (n = 22) and over 60 (n = 27) years. SARS-CoV-2-specific T-cell response was evaluated by IFN-γ-producing spot forming cells (SFCs) using a standardized ELISPOT assay. Virus neutralizing antibodies (VNA) against SARS-CoV-2 were measured by a blocking ELISA test and spike protein specific IgG (S-IgG) and IgA (S-IgA) antibodies—by semiquantitative ELISA. IFN-γ-producing SFCs, S-IgG, S-IgA and VNA significantly decreased 6–9 months after the second dose. After the third injection S-IgG and S-IgA markedly increased compared to T2 and reached the levels at T1. Of note, the highest values of VNA were observed at T3. No differences in the tested immune parameters were found between the two age groups. Data obtained showed that for a long period—6–9 months after a full course of immunization with mRNA vaccine, immune reactivity is present, but both cellular and humoral immune responses gradually decrease. The administration of a third dose mainly restores the specific humoral immune response against the SARS-CoV-2 virus.     

SARS CoV-2 infections in healthcare workers with a pre-existing T-cell response: a prospective cohort study

ObjectiveT-cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are observed in unexposed individuals. We evaluated the impact of this pre-existing cellular response on incident SARS-CoV-2 infections.MethodsThis was a follow-up study of 38 seronegative healthcare workers (HCWs) with previous evaluation of CD8+ and CD4+ T-cell responses after stimulation with SARS-CoV-2 structural proteins. Infection was considered in the presence of a positive RT-PCR test and/or confirmed seroconversion.ResultsTwenty of the 38 HCWs included (53%) had a previous specific CD8+ T-cell response to peptides encompassing the spike protein (S) in 13 (34%), the membrane (M) in 17 (45%), or/and the nucleocapsid (N) in three (8%). During a follow-up of 189 days (interquartile range (IQR) 172–195), 11 HCWs (29%) had an RT-PCR-positive test (n = 9) or seroconverted (n = 2). Median duration of symptoms was 2 days (IQR 0–7), and time to negative RT-PCR was 9 days (IQR 4–10). Notably, six incident infections (55%) occurred in HCWs with a pre-existing T-cell response (30% of those with a cellular response), who showed a significantly lower duration of symptoms (three were asymptomatic). Three of the six HCWs having a previous T-cell response continued to test seronegative. All the infected patients developed a robust T-cell response to different structural SARS-CoV-2 proteins, especially to protein S (91%).ConclusionA pre-existing T-cell response does not seem to reduce incident SARS-CoV-2 infections, but it may contribute to asymptomatic or mild disease, rapid viral clearance and differences in seroconversion.     

SARS-CoV-2 Antibody Response to the BNT162b2 mRNA Vaccine in Persons with Past Natural Infection

There are still no agreed guidelines on the vaccination of coronavirus disease 2019 (COVID-19) for previously infected patients. Here, we present two seropositive healthcare workers (HCWs) working in an isolation ward who recovered from COVID-19 in April 2020 and got vaccinated with BNT162b2 vaccine in March 2021. We have assessed the clinical course, vaccine-related adverse events, and antibody response after natural infection and after first and second dose vaccination. One of the two HCWs was asymptomatic during quarantine, but the other had mild upper respiratory infection symptoms 1 day before admission, and the symptoms continued for 9 days. There was no pneumonic infiltration in chest X-ray in both patients, and no COVID-19 specific treatment was administered. Total immunoglobulin antibody and neutralizing antibody to anti-spike protein receptor-binding domain of severe acute respiratory syndrome coronavirus 2 were confirmed to be present in both HCWs in blood tests performed at 2 weeks and 4 weeks after discharge. Antibody response to mRNA vaccination showed marked elevation after the first vaccination, which was 30–40 times higher than that of antibody titer after natural infection in each patient (83.2 U/mL vs. > 2,500 U/mL in patient 1; 61.6 U/mL vs. > 2,500 U/mL in patient 2). Signal inhibition rate of neutralizing antibodies was also increased to over 97%. Due to this increased effect, there was little difference in antibody levels after the first and second dose. Both patients 1 and 2 suffered more from adverse vaccine reactions after the second vaccination than from COVID-19 symptoms.     

Comparison of Antibody Response Elicited by ChAdOx1 and BNT162b2 COVID-19 Vaccine

BackgroundChAdOx1 and BNT162b2 vaccines are currently commonly used against coronavirus disease 2019 worldwide. Our study was designed to determine the serostatus and relative levels of anti-S and neutralizing antibodies in patients who were administered either ChAdOx1 or BNT162b2 vaccine. In addition, we investigated whether the antibody response to each vaccine differed according to sex and age.MethodsHealthcare workers (HCWs) at a general hospital who were vaccinated with two doses of either ChAdOx1 or BNT162b2 were invited to participate in this prospective cohort study. Blood samples of HCWs vaccinated with both ChAdOx1 doses over a period of 12 weeks were collected at weeks 4 and 8 post first vaccination and 2 weeks post second vaccination. Blood samples of HCWs vaccinated with BNT162b2 were collected in the third week after the first dose, and the second dose was then administered on the same day; two weeks post second dose (5 weeks after the first dose), blood samples were collected to assess the antibody response. The titers of anti-S antibodies against the severe acute respiratory syndrome coronavirus 2 spike (S) protein receptor-binding domain and the neutralizing antibodies in the collected blood were evaluated.ResultsOf the 309 HCWs enrolled in the study, 205 received ChAdOx1 and 104 received BNT162b2. Blood samples from participants receiving either the ChAdOx1 or BNT162b2 vaccine exhibited substantial anti-S and neutralizing antibody seropositivity subsequent to the second dose. All participants (100%) from both vaccine groups were seropositive for anti-S antibody, while 98% (201/205) of ChAdOx1-vaccinated individuals and 100% (104/104) of BNT162b2-vaccinated individuals were seropositive for neutralizing antibodies. The median levels of anti-S and neutralizing antibodies were significantly higher in the BNT162b2-vaccinated group than the ChAdOx1-vaccinated group; in particular, anti-S antibody titers of 1,020 (interquartile range, 571.0–1,631.0) U/mL vs. 2,360 (1,243–2,500) U/mL, P < 0.05, were recorded for the ChAdOx1 and BNT162b2 groups, respectively, and neutralizing antibody titers of 85.0 (65.9–92.1%) vs. 95.8 (94.4–96.6%), P < 0.05, were recorded for the ChAdOx1 and BNT162b2 groups, respectively. In the ChAdOx1 vaccine group, the neutralizing antibody level was significantly higher in women than in men (85.7 [70.3–92.5%] vs. 77.7 [59.2–91.0%], P < 0.05); however, the neutralizing antibody titer in the BNT162b2 vaccine group did not vary between the two sexes (95.9 [95.2–96.6%] vs. 95.2 [93.5–96.3%], P = 0.200). Analysis of the correlation of antibody profiles with age revealed that the levels of anti-S antibodies and signal inhibition rate (SIR) of neutralizing antibodies decreased significantly with age.ConclusionBoth the ChAdOx1- and BNT162b2-vaccinated groups showed high seropositivity for anti-S and neutralizing antibodies. The SIR of neutralizing antibodies in the ChAdOx1 vaccine group was higher in women than in men. Enhanced antibody responses were observed in participants vaccinated with BNT162b2 compared to those vaccinated with the ChAdOx1 vaccine.     

Association between a low response to rubella vaccination and reduced anti-severe acute respiratory syndrome coronavirus 2 immune response after vaccination with BNT162b2: a cross-sectional study

ObjectivesSome vaccinated individuals fail to acquire an adequate immune response against infection. We aimed to determine whether mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination could induce a sufficient immune response against SARS-CoV-2 in low responders to other vaccinations.MethodsUsing data from health-care workers who received two doses of the BNT162b2 vaccine (BioNTech/Pfizer), we conducted a single-centre, cross-sectional study to determine whether low responders to measles, rubella, and hepatitis B virus (HBV) vaccinations could acquire sufficient antibodies after SARS-CoV-2 vaccination. From May 2021 to June 2021, participants were tested for anti-SARS-CoV-2 spike (anti-S) IgG antibodies at least 2 weeks after the second dose of BNT162b2. The association between a low response to measles, rubella, and HBV vaccinations and the post-vaccination anti-S IgG titre was evaluated using the multivariable linear regression analysis.ResultsAll 714 participants were positive for the anti-S IgG titre (≥50.0 AU/mL) after two doses of BNT162b2 (median, 7126.8 AU/mL; interquartile range, 4496.2–11 296.8). There were 323 (45.2%), 131 (18.3%), and 43 (6.0%) low responders to measles, rubella, and HBV vaccinations, respectively. In the multivariable linear regression analysis, low responders to rubella vaccination had significantly low acquisition of the anti-S IgG titre after two doses of the BNT162b2 vaccine (standardized coefficient β, ?0.110; 95% CI, ?0.175 to ?0.044).ConclusionsA low response to rubella vaccination is a potential predictor of a reduced response to SARS-CoV-2 vaccination. Further studies are needed to determine whether a low response to rubella vaccination is associated with the durability of SARS-CoV-2 vaccination-induced immune response.     

The effect of a third BNT162b2 vaccine on breakthrough infections in health care workers: a cohort analysis

ObjectivesIn August 2021, 6 months after mass vaccination of the Israeli population with the two-dose BNT162b2 mRNA vaccine, a surge of coronavirus disease 2019 infections, mostly from the delta variant, appeared also among the vaccinated. In response, the Israeli Ministry of Health initiated a booster (third dose) vaccination program. We assessed the protective effect of the third dose among health care workers (HCWs).MethodsInfections with severe acute respiratory syndrome coronavirus 2 are monitored systematically among HCWs at the Hadassah tertiary care medical centre in Jerusalem, Israel. In this cohort, we included breakthrough infections, defined as those occurring >180 days since the second vaccine dose. The follow-up period lasted 120 days. We compared infection rates between HCWs who received the booster dose and those who received only the two-dose regimen.ResultsThe rate of breakthrough infections among HCWs who received only the two-dose regimen was 21.4% (85 of 398). The rate in the boosted group was 0.7% (35/4973; relative risk 30, 95% CI 20-50). Those results were seen in all age groups.DiscussionThe significantly lower rate of breakthrough infections in boosted HCWs indicates substantial protection by a third vaccine dose.     

Neutralization of alpha,gamma, and D614G SARS-CoV-2 variants by CoronaVac vaccine-induced antibodies

Vaccination generates a neutralizing immune response against SARS-CoV-2. The genomic surveillance is showing the emergence of variants with mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we report the neutralization potency against alpha, gamma, and D614G SARS-CoV-2 variants in 44 individuals that received two doses of CoronaVac vaccine, an inactivated SARS-CoV-2 vaccine. Plasma samples collected at 60 days after the second dose of CoronaVac were analyzed by the reduction of cytopathic effect in Vero E6 cells with the three infectious variants of SARS-CoV-2. Plasma showed lower neutralization with alpha (geometric mean titer [GMT] = 18.5) and gamma (GMT = 10.0) variants than with D614G (GMT = 75.1) variant. Efficient neutralization against the alpha and gamma variants was not detected in 31.8% and 59.1% of plasma, respectively. These findings suggest the alpha and gamma variants could escape from neutralization by antibodies elicited by vaccination. Robust genomic and biological surveillance of viral variants could help to develop effective strategies for the control of SARS-CoV-2.     

A triple-RBD-based mucosal vaccine provides broad protection against SARS-CoV-2 variants of concern

The rapid mutation and spread of SARS-CoV-2 variants urge the development of effective mucosal vaccines to provide broad-spectrum protection against the initial infection and thereby curb the transmission potential. Here, we designed a chimeric triple-RBD immunogen, 3Ro-NC, harboring one Delta RBD and two Omicron RBDs within a novel protein scaffold. 3Ro-NC elicits potent and broad RBD-specific neutralizing immunity against SARS-CoV-2 variants of concern. Notably, intranasal immunization with 3Ro-NC plus the mucosal adjuvant KFD (3Ro-NC + KFDi.n) elicits coordinated mucosal IgA and higher neutralizing antibody specificity (closer antigenic distance) against the Omicron variant. In Omicron-challenged human ACE2 transgenic mice, 3Ro-NC + KFDi.n immunization significantly reduces the tissue pathology in the lung and lowers the viral RNA copy numbers in both the lung (85.7-fold) and the nasal turbinate (13.6-fold). Nasal virologic control is highly correlated with RBD-specific secretory IgA antibodies. Our data show that 3Ro-NC plus KFD is a promising mucosal vaccine candidate for protection against SARS-CoV-2 Omicron infection, pathology and transmission potential.     

Heterologous high dose SARS-CoV-2 mRNA vaccine booster may improve immune response in seronegative kidney transplant recipients

IntroductionThree-dose mRNA vaccination against COVID-19 is unable to elicit a sufficient immune response in immunocompromised subjects.MethodsThe aim of the study was to conduct a retrospective evaluation of the efficacy of a heterologous mRNA booster with mRNA-1273 in constantly seronegative kidney transplant recipients (KTRs) after three doses of the BNT162b2 mRNA vaccine. Twelve seronegative KTRs received a mRNA-1273 booster 5 months after the third dose of BNT162b2.ResultsA total of 5 out of 12 patients (41.7%) seroconverted, with a mean titer of 353 BAU/ml.ConclusionsThe administration of a heterologous mRNA vaccine as a booster may be an effective alternative for achieving post-vaccination immunity in seronegative KTRs.