Neutralizing antibody responses in healthcare personnel after three doses of mRNA BNT162b2 vaccine and association with baseline characteristics and past SARS-CoV-2 infection

SARS-CoV-2 mRNA vaccine induces robust specific and cross-reactive IgG and unequal neutralizing antibodies in naive and previously infected people

Third dose of COVID-19 vaccine leads to seroconversion in 56% cancer patients that are seronegative after primary vaccination and a fourth can further boost immune response in patients with hematologic malignancies, which can be predicted by IgM and CD19 levels.

Third dose of COVID-19 vaccine leads to seroconversion in 56% cancer patients that are seronegative after primary vaccination and a fourth can further boost immune response in patients with hematologic malignancies, which can be predicted by IgM and CD19 levels.

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Article Figures and data Abstract Editor's evaluation Introduction Materials and methods Results Discussion Data availability References Decision letter Author response Article and author information Metrics Abstract Background: Although inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed. Methods: We enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests. Results: Our results revealed that binding antibody IgM peaked 14–28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The neutralized fraction subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89)–17.8% (16/90). Conclusions: Two doses of CoronaVac vaccine resulted in limited protection over a short duration. The inactivated vaccine booster can reverse the decrease of antibody levels to prime strain, but it does not elicit potent neutralization against Omicron; therefore, the optimization of booster procedures is vital. Funding: Key Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation; Explorer Program of Zhejiang Municipal Natural Science Foundation. Editor's evaluation This study presents important evidence that boosting with the Sinovac Coronavac inactivated vaccine would provide considerable protection from ancestral SARS-CoV-2 in terms of elicited neutralizing antibodies but would offer minimal protection against Omicron subvariants. The evidence supporting the claims of the authors is solid, although using a dilution series instead of one plasma dilution for Omicron neutralization would have strengthened the study. The work will be of very wide interest to the biomedical community and beyond, since it points to the need for a better booster vaccine in China. https://doi.org/10.7554/eLife.84056.sa0 Decision letter Reviews on Sciety eLife's review process Introduction The coronavirus disease 2019 (COVID-19), a global health emergency caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has led to unprecedented global healthcare and economic burdens (Clark et al., 2020). COVID-19 vaccines are indispensable for mitigating this situation and containing the ongoing pandemic, as shown by the decline in new and hospitalized COVID-19 cases since mass vaccination began (Rossman et al., 2021). Inactivated COVID-19 vaccines, such as CoronaVac and BBIBP-CorV, were proven to be generally safe and effective in adults in several clinical trials (Xia et al., 2022; Xia et al., 2020; Wu et al., 2021) and are widely used in China and abroad. Nevertheless, basic questions remain about the vaccine-induced longevity of immunity in the population and the rate of breakthrough infections (Kim et al., 2021). Several studies have gathered immunogenicity data on antibody kinetics after vaccination and showed that neutralizing titers induced by two doses of inactivated vaccine peaked in month 2 and declined to 33.89% by month 6 (Cheng et al., 2022). However, it is important to provide more data on the enhancement and attenuation of immunological protection after vaccination in real-world studies. The SARS-CoV-2 variants that have been classified as variants of interest or variants of concern (VOC) by the World Health Organization (WHO) are responsible for multiple waves of infection (Dyson et al., 2021) and the increased concerns about the protection provided by current vaccines (Mlcochova et al., 2021; Altmann et al., 2021). The Omicron (B.1.1.529) variant recently identified in South Africa has spread globally (Karim and Karim, 2021; Viana et al., 2022), raising concerns about the effectiveness of antibody therapies and vaccines to variants with multiple mutations (Flemming, 2022; VanBlargan et al., 2022; Suzuki et al., 2022; Meng et al., 2022). A recent real-world study in Israel suggested that a third dose of BNT162b2 vaccine was highly effective in preventing infection, severe disease, hospitalization, and death (Barda et al., 2021). Booster vaccines reinstate waning immunological memory and expand the breadth of immune responses to SARS-CoV-2 variants (Goldberg et al., 2021; Zhu et al., 2022; Chen et al., 2022; Cao et al., 2021; Planas et al., 2022). Therefore, the provision of booster vaccinations for SARS-CoV-2 is recommended by the WHO and is being implemented for fully vaccinated recipients in China and other countries. However, data are needed on the protective immune responses elicited by the boosters against VOC in mass vaccination campaigns. We explored the dynamic responses and durations of antibodies against SARS-CoV-2 in individuals within 1 year of being vaccinated with an inactivated COVID-19 vaccine and speculated on the protection provided based on the attenuation of neutralizing antibody levels. Furthermore, we evaluated the presence of neutralizing antibodies against Delta and Omicron in volunteers boosted with a third dose of inactivated vaccine. Materials and methods Study design and participants Request a detailed protocol The cross-sectional investigation was conducted in five counties of Zhejiang Province, mainland China (Xihu, Yuecheng, Shangyu, Kaihua, and Longyou Districts), after nationwide COVID-19 vaccinations from May to October 2021. Potential participants aged 18–59 years who had no prior vaccinations or were vaccinated with one or two doses of CoronaVac (Sinovac Life Sciences, Beijing, China) were recruited from the community. Individuals with a history of infection with SARS-CoV-2 (based on epidemic surveillance system) or the use of blood products or immunosuppressive drugs were excluded. We randomly enrolled 1067 volunteers, including those on day 0 (V-0, no vaccination), day 14±2 (V1-14d), and day 28±3 (V1-28d) after the first vaccine dose, and day 30±3 (V2-1m), day 90±7 (V2-3m), day 180±14 (V2–6 m), day 270±14 (V2-9m), and day 365±30 (V2-12m) after the second dose and collected their venous blood samples (3–5 ml) to detect serum antibody levels (Figure 1A). This was not a longitudinal survey, as different subjects were enrolled at each point in time. We employed a questionnaire survey at blood drawing visits to gather demographic information. Figure 1 Download asset Open asset Schedule of sample collection. (A) Cross-sectional survey: a total of 1067 participants aged 18–59 were enrolled in five counties in Zhejiang, China. The participants had no previous vaccination or were vaccinated with one or two doses of CoronaVac. Venous blood (3–5 ml) was collected on day 0 (V-0, no vaccination), day 14±2 (V1-14d), and day 28±3 (V1-28d) after the first dose, and day 30±3 (V2-1m), day 90±7 (V2-3m), day 180±14 (V2-6m), day 270±14 (V2-9m), and day 365±30 (V2-12m) after the second dose. (B) Prospective cohort study: 90 healthy adults aged 18–80 years in Jiaxing city were recruited and administered 4 µg/0.5 mL of CoronaVac following a 3-shot vaccine schedule 28 days and 6 months apart. Following that, venous blood was collected from recipients at five timepoints: day 0 (Pre-V, before vaccination), day 30±3 (V2-1m), day 90±7 (V2-3m), and day 180±14 (V2-6m) after the second dose, and day 30±3 (V3-1m) after the third dose. In the prospective cohort study, we recruited 90 healthy adults aged 18–80 years from Jiaxing city, Zhejiang, in June 2021. The main exclusion criteria included previous or later SARS-CoV-2 infection; allergy to any ingredient included in the vaccine; those who had received any blood products or any research medicines or vaccines in the past month; those who had uncontrolled epilepsy or other serious neurological diseases, acute febrile disease, acute onset of chronic diseases, or uncontrolled severe chronic diseases; and those who were unable to comply with the study schedule. Subjects were administered 4 µg/0.5 mL of CoronaVac following a 3-shot vaccine schedule 28 days and 6 months apart. Following that, venous blood (3–5 ml) was collected from recipients at five time points: day 0 (Pre-V, before vaccination), day 30±3 (V2-1m), day 90±7 (V2-3m), and day 180±14 (V2-6m) after the second dose, and day 30±3 (V3-1m) after the third dose (Figure 1B). SARS-CoV-2-specific IgG and IgM assay Request a detailed protocol The commercial detection kit iFlash-2019-nCoV NAb assay (Shenzhen YHLO Biotech Co. Ltd., Shenzhen, China) was employed to measure the levels of IgG and IgM against SARS-CoV-2 spike glycoprotein (S) and nucleocapsid protein (N) by chemiluminescence immunoassay. Briefly, serum samples were allowed to form a complex with SARS-CoV-2 S- and N-protein antigen-coated paramagnetic microparticles, then an acridinium-ester-labeled ACE2 conjugate was added to competitively combine with the particles, forming another reaction mixture. The analyzer converted relative light units (RLUs) into an antibody titer (AU/mL) through a two-point calibration curve. An inverse relationship existed between the amount of SARS-CoV-2 NAb in the sample and the RLUs detected by the iFlash optical system. According to the manufacturer, titers of ≥10.0 AU/mL and ≥1.0 AU/mL are considered positive (or reactive) for IgG and IgM, respectively. IgG and IgM against SARS-CoV-2 receptor binding domain (RBD) were detected using a commercial ELISA kit (Bioscience Biotech Co. Ltd., Chongqing, China). The positive cutoff values for RBD-specific IgG and IgM antibodies were defined as titers of ≥1.0 AU/mL. All tests were performed according to the manufacturer's protocols (Chan et al., 2021; Li et al., 2021). Live virus neutralization antibody assays Request a detailed protocol The levels of neutralizing antibodies to live SARS-CoV-2 were assessed by the reduction in the cytopathic effect (CPE) in Vero cells with infectious SARS-CoV-2 strain 19nCoVCDC-Tan-HB01 (HB01) in a BSL-3 laboratory (Zhang et al., 2021). Briefly, serum samples were heat-inactivated for 30 min at 56 °C and successively diluted from 1:4 to the required concentration in a twofold series. An equal volume of challenge solution containing 100 TCID50 virus was added. After neutralization in a 37 °C incubator for 2 h, a 1.5–2.5×105 /ml cell suspension was added to the wells. The CPE (cytopathic effect) on VeroE6 cells was analyzed at 4 days post-infection. NT50 (50% neutralization titer, the reciprocal of the highest dilution protecting 50% of the cells from virus challenge) was used to show the neutralization titers. NT50 above 1:4 was defined as positive. Pseudovirus-based neutralization test Request a detailed protocol Serum samples were also quantified for their content of SARS-CoV-2-neutralizing antibodies to wildtype (Wuhan), Delta (B.1.617.2), and Omicron (B.1.1.529) using the pseudovirus-based virus neutralization test (Nie et al., 2020). Briefly, serum samples and a positive or negative reference sample were each diluted 50 times with phosphate-buffered saline combined with 50 µl of pseudovirus diluent per well in a 96-well plate. The mixed sample/pseudovirus was incubated at 37 °C and 5% CO2 for 1 hr. A 2×105 /ml BHK-21-ACE2 cell suspension was added to each well of the plate containing the sample/pseudovirus mixture, then the plate was incubated in a 37 °C and 5% CO2 cell incubator for 48 hr. Finally, the number of green-fluorescence-protein-positive cells per well was read with a porous plate imager (Tecan, Shanghai, SparkCyto). The results were determined by comparing the neutralized fraction using the following calculation: (1 – (fluorescence value of each well/average virus control value))×100% (Karaba et al., 2022). At least four wells were left blank for calibration to 0% inhibition. Statistical analysis Request a detailed protocol Sex, age, BMI, and other clinical characteristics were collected for each vaccination recipient. We used the medians and interquartile ranges (IQR) for age, and numbers (percentages) for categorical variables. Specific binding antibodies against SARS-CoV-2 (IgG, IgM) and neutralized fraction of SARS-CoV-2-neutralizing antibodies are presented as mean ± standard error (SEM). Neutralizing antibodies are presented as geometric mean titers (GMT), and their 95% confidence interval (CI) was calculated with Student's t distribution on log-transformed data and then back-transformed. Comparisons of titer-level differences between the two groups were performed using the paired Student's t-test. One-way analysis of variance (one-way ANOVA) was used to analyze the differences between the mean values at different timepoints. Correlations between NAb titers, neutralized fraction, and IgG/IgM levels were evaluated by Pearson's correlation coefficient. Statistical tests were two-sided, and we considered p-values of less than 0.05 as statistically significant. All statistical analyses were conducted in SPSS 18.0 (IBM Corporation, Armonk, NY, USA) and GraphPad Prism 9 (San Diego CA, USA). Results Study participant characteristics We conducted a cross-sectional survey and recruited 1067 volunteers who had no vaccination or were vaccinated with one or two doses of CoronaVac in October 2020 or later in this multicenter study. Participants ranged in age from 18 to 59 years, with a median age of 40 years (IQR, [32-48]), and there was a balanced distribution of males (43.3%) and females (56.7%). Samples were collected at eight timepoints, including V-0 (n=91), V1-14d (n=125), and V1-28d (n=91) after vaccination with the first dose and V2-1m (n=100), V2-3m (n=110), V2-6m (n=160), V2-9m (n=190), and V2-12m (n=200) after vaccination with the second dose (Figure 1A). Demographic data for the vaccine recipients are summarized in Table 1. Table 1 Baseline characteristics and anti-S/N antibody levels in the cross-sectional study. V-0N=91V1-14dN=125V1-28dN=91V2-1mN=100V2-3mN=110V2-6mN=160V2-9mN=190V2-12mN=200Median age (IQR), years38(31,47)39(34,47)38(31,47)40(32,50)41(33,55)41(31,48)41(31,48)41(34,49)SexMale3745374954808575Female548054515680105125IgMConcentration (AU/ml)0.4±0.025.1±1.05.1±0.91.4±0.20.4±0.10.3±0.040.3±0.040.2±0.03Seropositivity (%)3.357.675.833.03.64.44.72.0IgGConcentration (AU/ml)0.6±0.13.7±0.564.3±5.879.7±5.729.4±2.410.5±0.98.9±1.06.8±0.9Seropositivity (%)0.07.297.897.088.232.522.113.5 Data are n (%) or median (IQR), or mean ± SEM. The seropositivity rate is when positive concentration of anti-S/N antibody is 10.0 AU/mL (IgG) and ≥1.0 AU/mL (IgM) or more. Table 1—source data 1 Baseline characteristics and anti-S/N antibody levels in the cross-sectional study. https://cdn.elifesciences.org/articles/84056/elife-84056-table1-data1-v2.xlsx Download elife-84056-table1-data1-v2.xlsx In the prospective cohort study, we recruited 90 healthy adults who met all inclusion criteria and no exclusion criteria, including 40 (44.4%) males and 50 (56.6%) females with a median age of 64 years (IQR, [39-70]), 33.3% of whom had a BMI of ≥24.0 kg/m2, and 33.3% had ≥1 underlying comorbidity (most commonly hypertension and diabetes) (Table 2). The participants were administered a standard dose of the CoronaVac vaccine on days 0 and 28 and a booster dose after month 7. Blood samples were collected at study visit 0 (Pre-V) before vaccination; visit 1 (V2-1m), visit 2 (V2-3m), and visit 3 (V2-6m) after vaccination with the second dose; and visit 4 (V3-1m) after the third dose (Figure 1B). None of participants had a history of laboratory-confirmed SARS-CoV-2 infection. Table 2 Baseline characteristics for the prospective cohort. N=90P (%)Age group (years)18–442831.145–642123.365–804145.6SexMale4044.4Female5055.6BMI (kg/m2) <18.533.318.5–23.95763.4≥243033.3Chronic conditionsYes3033.3No6066.7 Table 2—source data 1 Baseline characteristics for the prospective cohort. https://cdn.elifesciences.org/articles/84056/elife-84056-table2-data1-v2.xlsx Download elife-84056-table2-data1-v2.xlsx Dynamics of antibody responses to primary vaccination To explore the dynamic changes in humoral immune responses to the inactivated COVID-19 vaccine, we first evaluated the recipients' anti-S/N IgM and IgG development at different timepoints (Figure 2A). The titer of anti-S/N-IgM on day 0 increased to 5.1±1.0 AU/ml on day 28 after the first dose, though the seropositivity rate was 57.6%. The seropositivity rates of anti-S/N-IgM reached a peak of 75.8% (5.1±0.9 AU/ml) approximately 28 days after the first dose, while the seropositivity of anti-S/N-IgG reached 97.0% (79.7±5.7 AU/ml) approximately 28 days after the second dose. The titer of anti-S/N-IgM rapidly declined to 1.4±0.2 AU/ml, which is close to the threshold value, 28 days after the second dose, while anti-S/N-IgG declined to 10.5±0.9 AU/ml during month 6 after the second dose. A small percentage of the population still had anti-S/N IgG antibodies, with seropositivity rates of 22.1% and 13.5%, respectively, during months 9 and 12 after the second dose (Table 1). Figure 2 Download asset Open asset Anti-SARS-CoV-2-specific IgG and IgM levels induced by inactivated COVID-19 vaccines. (A, B) Dynamic changes in anti-S/ N- (A) and anti-RBD- (B) specific IgM/IgG in serum samples from CoronaVac-vaccinated participants at V-0, V1-14d, V1-28d, V2-1m, V2-3m, V2-6m, V2-9m, and V2-12m. (C) Correlation between levels of anti-S/anti-N- and anti-RBD-specific antibodies in IgM (left) or IgG (right) at V2-1m. Dates are presented as mean ± SEM. One-way analysis of variance was used for comparison. Correlations were assessed using Pearson's correlation coefficient. Two-tailed p values were calculated. ns, not significant, * p<0.05, **p<0.01, ***p<0.001. Figure 2—source data 1 Anti-SARS-CoV-2-specific IgG and IgM levels induced by inactivated COVID-19 vaccines. https://cdn.elifesciences.org/articles/84056/elife-84056-fig2-data1-v2.xlsx Download elife-84056-fig2-data1-v2.xlsx S protein RBD binding to the angiotensin converting enzyme 2 (ACE2) receptor is a critical initial step in the entry of SARS-CoV-2 into target cells (Zuo et al., 2022). We detected the anti-RBD IgM and IgG levels in the serum samples at several timepoints after the second dose (Figure 2B). The results were similar to those for anti-S/N antibodies, showing peak levels of anti-RBD-IgM (1.8±0.4 AU/ml) and anti-RBD-IgG (18.0±1.6 AU/ml) 1 month after the second dose, after which, the levels of both gradually waned. Furthermore, analysis showed a good correlation between IgM or IgG and anti-S/N and anti-RBD antibodies (R2=0.7364, p<0.001; R2=0.7170, p<0.001, Figure 2C). Participants were tested with a live virus-based and pseudovirus-based neutralization assay. As depicted in Figure 3A, samples were negative for NAbs at the pre-vaccine baseline, and 87.0% of recipients had a NAb titer greater than 1:4 after the administration of the second dose, along with a GMT of 20.2 (95% the decline in month the values not between month 1 and month 3 However, 12 months after of the population were with a GMT of (95% the neutralized fraction for the pseudovirus was at 1 month after the second dose and slightly (Figure Correlation analysis showed correlation between NAb titers and anti-S/N IgM NAb titers and anti-RBD IgM NAb titers and anti-S/N IgG neutralized fraction and anti-S/N IgM neutralized fraction and anti-RBD IgM between NAb titers and anti-RBD IgG NAb titer and neutralized fraction neutralized fraction and anti-S/N IgG neutralized fraction and anti-RBD IgG Figure 3 Download asset Open asset Neutralizing antibodies induced by inactivated COVID-19 vaccines. (A, B) Dynamic changes in GMT of NAb titer (A) and neutralized fraction (B) in serum samples from CoronaVac-vaccinated participants at V-0, V2-1m, V2-3m, V2-6m, V2-9m, and V2-12m. (C) Correlation levels of and GMT of NAb titer, and neutralized fraction at V2-1m. One-way analysis of variance was used for comparison. Correlations were assessed using Pearson's correlation coefficient. Two-tailed p values were calculated. ns, not significant, * p<0.05, **p<0.01, ***p<0.001. Figure data 1 Neutralizing antibodies induced by inactivated COVID-19 vaccines. Download Antibody responses before and after booster the of antibody responses to the CoronaVac vaccine, we the cohort of 90 individuals booster to 6 months after the second dose, and the are shown in the in Figure At month 1 after the second dose, the seropositivity of anti-S/N and anti-RBD were and and reached peak levels of AU/ml and AU/ml, respectively. After which over time to AU/ml and AU/ml, respectively, in month of the booster dose levels to AU/ml and AU/ml at month 1 and from the (Figure Figure 4 Download asset Open asset Comparisons of IgG and IgM levels and neutralizing before and after booster (A, B) Dynamic changes in anti-S/N IgM and IgG GMT of NAb titer, and neutralized fraction (B) in serum samples from CoronaVac-vaccinated participants at V-0, V2-1m, V2-3m, V2-6m, and One-way analysis of variance was used for comparison. Two-tailed values were calculated. ns, not significant, * Figure data 1 Comparisons of IgG and IgM levels and neutralizing before and after booster Download After the primary two doses and the third booster dose, a similar was in the two neutralization test results (Figure The GMT of the NAb titer peaked at (95% and to (95% at month which was a attenuation of the peak value, with the total seropositivity from to After the booster dose, the GMT increased to (95% that at month which was than the first The showed that the neutralized fraction for the pseudovirus peaked at ± before gradually to ± in month 6 but increased to ± after the The levels of antibodies by age BMI, and chronic at each point are presented in Table The titer showed a statistically age groups during months after the primary but there was no after the booster dose. a NAb titer than males (95% (95% after the booster However, there were no statistically differences in antibody titer levels between the different BMI or chronic Table 3 The of age to GMT and The seropositivity rate is when positive NT50 is above geometric mean titers. Antibody responses to Delta and Omicron variants in the RBD to a reduction in the antibody neutralization of VOC et al., 2021). We measured the levels of neutralizing antibodies against the Delta and Omicron (B.1.1.529) variants from serum samples in month 1 after the primary and booster (Figure in individuals vaccinated with two doses of the inactivated vaccine, the neutralized fraction for the pseudovirus against the Delta variant in the Omicron variant were with that against the strain However, the booster vaccination to a in neutralizing against the The neutralized fraction subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron after booster dose of inactivated vaccine. The response rate fraction for Omicron rose from 7.9% in the primary two doses to after booster dose. Therefore, results showed that the booster of Coronavac not elicit potent neutralization against Omicron although booster dose slightly increased antibody Figure Download asset Open asset Antibody responses to Delta and Omicron fraction of strain, Delta (B.1.617.2), and Omicron (B.1.1.529) variants for CoronaVac and as evaluated by pseudovirus-based neutralization The paired Student's and analysis of variance were used for comparison. Two-tailed p values were calculated. * p<0.05, **p<0.01, ***p<0.001. Figure data 1 Antibody responses to Delta and Omicron Download Discussion Inactivated vaccines have been widely used to the COVID-19 and rate and number of et al., 2021; et al., 2021). However, there has been no correlation between and protection or duration of protection for inactivated COVID-19 vaccines. Our study of antibody kinetics showed that IgM levels peaked 14–28 days after one dose of CoronaVac, after which declined Two doses of the inactivated vaccine induced levels of IgG and neutralizing antibodies, which peaked approximately 1 month after vaccination and declined slightly over time. The vaccine-induced immunity had waned to levels 6 months later and became undetectable in the majority of individuals 12 months studies have shown that antibody responses decline over time after an initial COVID-19 Following vaccination with the BNT162b2 vaccine, humoral responses were after 6 months healthcare in Israel of years of age or et al., 2021). In a of levels was following and BNT162b2 with levels by about and days and days or more after the second dose, et al., 2021). was that the immunity provided by inactivated COVID-19 vaccines, such as CoronaVac and for 6 with a NAb GMT of and in month 6 after the two doses and seropositivity of and (Cheng et al., 2022; et al., 2022). In study, the seropositivity and GMT of CoronaVac at and (95% respectively, for 6 months after the primary which is to prior data on inactivated vaccines (Cheng et al., 2022), although the immunogenicity was than that of other of COVID-19 vaccines. However, the neutralization antibody response levels of different vaccines are to of a of laboratory methods for SARS-CoV-2 neutralization and differences in et al.,

Serum antibodies induced by CoronaVac tended to decrease over time, even though vaccinated with the homologous booster dose, and Delta and Omicron variants may be able to more efficiently evade the antibodies with time.

Serum antibodies induced by CoronaVac tended to decrease over time, even though vaccinated with the homologous booster dose, and Delta and Omicron variants may be able to more efficiently evade the antibodies with time.

Immunosuppression impaired the immunogenicity of inactivated SARS-CoV-2 vaccine in non-dialysis kidney disease patients

mRNA COVID-19 Vaccine for People with Kidney Failure: Hope but Prudence Warranted.

BackgroundDefining the protective thresholds against the severe-acute-respiratory-syndrome-related corona virus-2 pandemic is a crucial challenge. To reduce the risks of severe disease, hospitalization, and death, various COVID-19 vaccines have been rapidly developed.Aim of the workThis study aimed to assess the impact of three common COVID-19 vaccine types; two mRNA COVID-19 vaccines: (Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273), one adenoviral vector vaccine: Oxford/AstraZeneca’s ChAdOx1, and one inactivated vaccine (Sinovac Biotech/China’s Sinovac) on the level of neutralizing antibodies, considering factors such as vaccine type, demographic characteristics, and hybrid immunity. We conducted a direct comparative analysis involving 300 healthcare workers, both with and without prior SARS-CoV-2 infection (B.1, C.36.3, and AY.32 (Delta) variants). Neutralizing antibodies levels were measured at baseline (before vaccination), before the second dose, and six months after the second dose.ResultsThe results showed a significant increase in neutralizing antibodies levels after complete vaccination with all vaccine types. Among healthcare workers, those vaccinated with mRNA vaccines (Moderna or Pfizer) exhibited the highest neutralizing antibodies titers, followed by AstraZeneca, and finally Sinovac with the lowest titer. On studying the effect of previous COVID-19 infection after vaccination, no significant difference in neutralizing antibodies levels was observed between healthcare workers vaccinated with mRNA or AstraZeneca vaccines, both with prior COVID-19 infection, following the first and six months after the second dose.ConclusionThese findings suggest that individuals with prior COVID-19 may only require a single dose of mRNA or AstraZeneca vaccines to achieve a similar level of immunization as those without prior COVID-19 who completed the vaccination program.HighlightsThere is a significant increase in neutralizing antibodies levels after complete vaccination against COVID-19Vaccination with mRNA vaccines exhibits the highest neutralizing antibodies titers.Vaccination with Sinovac exhibits the lowest neutralizing antibodies titers.Graphical abstract

BackgroundPatients with chronic lymphocytic leukemia (CLL) have reduced seroconversion rates and lower binding antibody (Ab) and neutralizing antibody (NAb) titers than healthy individuals following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccination. Here, we dissected vaccine-mediated humoral and cellular responses to understand the mechanisms underlying CLL-induced immune dysfunction.Methods and findingsWe performed a prospective observational study in SARS-CoV-2 infection-naïve CLL patients (n = 95) and healthy controls (n = 30) who were vaccinated between December 2020 and June 2021. Sixty-one CLL patients and 27 healthy controls received 2 doses of the Pfizer-BioNTech BNT162b2 vaccine, while 34 CLL patients and 3 healthy controls received 2 doses of the Moderna mRNA-1273 vaccine. The median time to analysis was 38 days (IQR, 27 to 83) for CLL patients and 36 days (IQR, 28 to 57) for healthy controls. Testing plasma samples for SARS-CoV-2 anti-spike and receptor-binding domain Abs by enzyme-linked immunosorbent assay (ELISA), we found that all healthy controls seroconverted to both antigens, while CLL patients had lower response rates (68% and 54%) as well as lower median titers (23-fold and 30-fold; both p < 0.001). Similarly, NAb responses against the then prevalent D614G and Delta SARS-CoV-2 variants were detected in 97% and 93% of controls, respectively, but in only 42% and 38% of CLL patients, who also exhibited >23-fold and >17-fold lower median NAb titers (both p < 0.001). Interestingly, 26% of CLL patients failed to develop NAbs but had high-titer binding Abs that preferentially reacted with the S2 subunit of the SARS-CoV-2 spike. Since these patients were also seropositive for endemic human coronaviruses (HCoVs), these responses likely reflect cross-reactive HCoV Abs rather than vaccine-induced de novo responses. CLL disease status, advanced Rai stage (III-IV), elevated serum beta-2 microglobulin levels (β2m >2.4 mg/L), prior therapy, anti-CD20 immunotherapy (<12 months), and intravenous immunoglobulin (IVIg) prophylaxis were all predictive of an inability to mount SARS-CoV-2 NAbs (all p ≤ 0.03). T cell response rates determined for a subset of participants were 2.8-fold lower for CLL patients compared to healthy controls (0.05, 95% CI 0.01 to 0.27, p < 0.001), with reduced intracellular IFNγ staining (p = 0.03) and effector polyfunctionality (p < 0.001) observed in CD4+ but not in CD8+ T cells. Surprisingly, in treatment-naïve CLL patients, BNT162b2 vaccination was identified as an independent negative risk factor for NAb generation (5.8, 95% CI 1.6 to 27, p = 0.006). CLL patients who received mRNA-1273 had 12-fold higher (p < 0.001) NAb titers and 1.7-fold higher (6.5, 95% CI 1.3 to 32, p = 0.02) response rates than BNT162b2 vaccinees despite similar disease characteristics. The absence of detectable NAbs in CLL patients was associated with reduced naïve CD4+ T cells (p = 0.03) and increased CD8+ effector memory T cells (p = 0.006). Limitations of the study were that not all participants were subjected to the same immune analyses and that pre-vaccination samples were not available.ConclusionsCLL pathogenesis is characterized by a progressive loss of adaptive immune functions, including in most treatment-naïve patients, with preexisting memory being preserved longer than the capacity to mount responses to new antigens. In addition, higher NAb titers and response rates identify mRNA-1273 as a superior vaccine for CLL patients.

Longitudinal COVID-19-vaccination-induced antibody responses and Omicron neutralization in patients with lung cancer.

Infliximab and Tofacitinib Attenuate Neutralizing Antibody Responses Against SARS-CoV-2 Ancestral and Omicron Variants in Inflammatory Bowel Disease Patients After 3 Doses of COVID-19 Vaccine

Booster doses for inactivated COVID-19 vaccines: if, when, and for whom

Antibody titers and protection against a SARS-CoV-2 infection