scholarly journals Does reactogenicity after a second injection of the BNT162b2 vaccine predict spike IgG antibody levels in healthy Japanese subjects?

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257668
Author(s):  
Masaaki Takeuchi ◽  
Yukie Higa ◽  
Akina Esaki ◽  
Yosuke Nabeshima ◽  
Akemi Nakazono

Background Adverse reactions are more common after the second injection of messenger RNA vaccines such as Pfizer/BioNTech’s BNT162b2. We hypothesized that the degree and severity of reactogenicity after the second injection reflects the magnitude of antibody production against the SARS CoV-2 virus spike protein (spike IgG). Methods and results Blood samples were obtained from 67 Japanese healthcare workers three weeks after the first injection and two weeks after the second injection of the BNT162b2 vaccine to measure spike IgG levels. Using questionnaires, we calculated an adverse event (AE) score (0–11) for each participant. The geometric mean of spike IgG titers increased from 1,047 antibody units (AU/mL) (95% confidence interval (95% CI): 855–1282 AU/mL) after the first injection to 17,378 AU/mL (95% CI: 14,622–20,663 AU/mL) after the second injection. The median AE score increased from 2 to 5. Spike IgG levels after the second injection were negatively correlated with age and positively correlated with spike IgG after the first injection. AE scores after the second injection were not significantly associated with log-transformed spike IgG after the second injection, when adjusted for age, sex, AE score after the first injection, and log-transformed spike IgG after the first injection. Conclusions Although the sample size was relatively small, reactogenicity after the second injection may not accurately reflect antibody production.

2021 ◽  
Author(s):  
Masaaki Takeuchi ◽  
Yukie Higa ◽  
Akina Esaki ◽  
Yosuke Nabeshima ◽  
Akemi Nakazono

Adverse reactions are more common after the second injection of messenger RNA vaccines such as Pfizer/BioNTech's BNT162b2. We hypothesized that the degree and severity of reactogenicity after the second injection reflects the magnitude of antibody production against the SARS CoV-2 virus spike protein (spike IgG). Blood samples were obtained from 67 healthy Japanese healthcare workers three weeks after the first injection and two weeks after the second injection of the BNT162b2 vaccine to measure spike IgG levels. Using questionnaires, we calculated an adverse event (AE) score (0-11) for each participant. The geometric mean of spike IgG titers increased from 1,047 antibody units (AU/mL) (95% CI: 855±1282 AU/mL) after the first injection to 17,378 AU/mL (14,622±20,663 AU/mL) after the second injection. The median AE score increased from 2 to 5. Spike IgG levels after the second injection were negatively correlated with age and positively correlated with spike IgG after the first injection. AE scores after the second injection were not significantly associated with log-transformed spike IgG after the second injection, when adjusted for age, sex, and log-transformed spike IgG after the first injection. Although the sample size was relatively small, reactogenicity after the second injection may not accurately reflect antibody production.


Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1063
Author(s):  
Jürgen Held ◽  
Jan Esse ◽  
Koray Tascilar ◽  
Philipp Steininger ◽  
Kilian Schober ◽  
...  

mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as BNT162b2 (Comirnaty®), have proven to be highly immunogenic and efficient but also show marked reactogenicity, leading to adverse effects (AEs). Here, we analyzed whether the severity of AEs predicts the antibody response against the SARS-CoV-2 spike protein. Healthcare workers without prior SARS-CoV-2 infection, who received a prime-boost vaccination with BNT162b2, completed a standardized electronic questionnaire on the duration and severity of AEs. Serum specimens were collected two to four weeks after the boost vaccination and tested with the COVID-19 ELISA IgG (Vircell-IgG), the LIAISON® SARS-CoV-2 S1/S2 IgG CLIA (DiaSorin-IgG) and the iFlash-2019-nCoV NAb surrogate neutralization assay (Yhlo-NAb). A penalized linear regression model fitted by machine learning was used to correlate AEs with antibody levels. Eighty subjects were enrolled in the study. Systemic, but not local, AEs occurred more frequently after the boost vaccination. Elevated SARS-CoV-2 IgG antibody levels were measured in 92.5% of subjects with Vircell-IgG and in all subjects with DiaSorin-IgG and Yhlo-NAb. Gender, age and BMI showed no association with the antibody levels or with the AEs. The linear regression model identified headache, malaise and nausea as AEs with the greatest variable importance for higher antibody levels (Vircell-IgG and DiaSorin-IgG). However, the model performance for predicting antibody levels from AEs was very low for Vircell-IgG (squared correlation coefficient r2 = 0.04) and DiaSorin-IgG (r2 = 0.06). AEs did not predict the surrogate neutralization (Yhlo-NAb) results. In conclusion, AEs correlate only weakly with the SARS-CoV-2 spike protein antibody levels after COVID-19 vaccination with BNT162b2 mRNA.


2021 ◽  
Vol 10 (17) ◽  
pp. 3817
Author(s):  
Alexandre Vallée ◽  
Marc Vasse ◽  
Laurence Mazaux ◽  
Brigitte Bonan ◽  
Carline Amiel ◽  
...  

Background: There is a small amount of immunological data on COVID-19 heterologous vaccination schedules in humans. We assessed the immunogenicity of BNT162b2 (Pfizer/BioNTech) administered as a second dose in healthcare workers primed with ChAdOx1-S (Vaxzevria, AstraZeneca). Methods: 197 healthcare workers were included in a monocentric observational study in Foch hospital, France, between June and July 2021. The main outcome was the immunogenicity measured by serum SARS-CoV-2 IgG antibodies. Results: 130 participants received the ChAdOx1-S/BNT vaccine and 67 received the BNT/BNT vaccine. The geometric mean of IgG antibodies was significantly higher in the BNT/BNT vaccine group compared to the ChAdOx1-S/BNT vaccine group, namely 10,734.9, 95% CI (9141.1–12,589.3) vs. 7268.6, 95% CI (6501.3–8128.3), respectively (p < 0.001). However, after adjustment for time duration between the prime and second vaccinations, no significant difference was observed (p = 0.181). A negative correlation between antibody levels and time duration between second dose and serology test was observed for the BNT/BNT vaccine (p < 0.001), which remained significant after adjustment for all covariates (p < 0.001), but not for the ChAdOx1-S/BNT vaccine (p = 0.467). Conclusions: Heterologous and homologous schedules of ChAdOx1-S and BNT vaccines present robust immune responses after the second vaccination. The results observed were equivalent after adjustment for covariates and emphasize the importance of flexibility in deploying mRNA and viral vectored vaccines. Nevertheless, applying the ChAdOx1-S schedule vaccination for the heterologous second dose of BNT was associated with decreased IgG antibody levels compared to the homologous BNT/BNT vaccination.


2021 ◽  
Author(s):  
Shohei Yamamoto ◽  
Akihito Tanaka ◽  
Norio Ohmagari ◽  
Koushi Yamaguchi ◽  
Kazue Ishitsuka ◽  
...  

Background: The effect of heat–not–burn (HNB) tobacco product use and moderate alcohol drinking on immunogenicity to coronavirus disease (COVID–19) vaccines remain elusive. This study aimed to examine the association of tobacco product use and alcohol consumption with anti–SARS–CoV–2 spike IgG antibody titers after the BNT162b2 vaccine. Methods: Participants were 3,457 fully vaccinated healthcare workers in the 4 national centers for advanced medical and research in Japan. Smoking status and alcohol consumption were assessed via a questionnaire, and anti–SARS–CoV–2 spike IgG titers were measured by chemiluminescent enzyme immunoassay using serum collected on the median of 64 days after the second vaccination. Multilevel linear regression models were used to estimate the geometric mean titers (GMT) and the ratios of means (RoM) between groups. Results: Of vaccinated participants, 99.5% (3,440/3,457) were seropositive. Compared with never-smokers (GMT=119), IgG antibody titers were significantly lower among HNB tobacco users (including those who also smoked cigarettes) (GMT=105; RoM=0.88 [95%CI: 0.78–0.99]) and exclusive cigarettes smokers (GMT=96; RoM=0.81 [95%CI: 0.71–0.92]). Compared with non-drinkers of alcohol (GMT=123), alcohol drinkers consuming <1 go/day (GMT=114; RoM=0.93 [95%CI: 0.88–0.98]), 1–1.9 go/day (GMT=105; RoM=0.85 [95%CI: 0.79–0.93]), and ≥2 go/day (GMT=101; RoM=0.82 [95%CI: 0.72–0.94]) had significantly lower antibody titers (P for trend<0.01). Spline analysis showed a large reduction of antibody until around 1 go/day of alcohol consumption, and then they gradually decreased. Conclusions: Results suggest that in addition to conventional cigarette smoking and heavy alcohol drinking, use of HNB tobacco products and moderate alcohol drinking may be predictors of lower immunological response to COVID–19 vaccine.


2010 ◽  
Vol 17 (5) ◽  
pp. 836-839 ◽  
Author(s):  
Daniel J. Hackett ◽  
Changpin Zhang ◽  
Carla Stefanescu ◽  
Robert F. Pass

ABSTRACT Measurement of antibody to cytomegalovirus (CMV) glycoprotein B (gB) is valuable in the assessment of the antibody response to infection and to gB-containing vaccines. For this purpose, an enzyme-linked immunosorbent assay (ELISA) with a recombinant CMV gB molecule as the antigen was evaluated. Sera from 168 anti-CMV IgG-positive and 100 seronegative subjects were used to evaluate the anti-gB antibody assay. A cutoff optical density (OD) that would distinguish gB antibody-positive from -negative sera was established. Titers of antibody to gB determined by endpoint dilution were compared with those calculated using regression analysis. The run-to-run and interoperator reproducibilities of results were measured. The mean OD + 5 standard deviations from 50 anti-CMV IgG antibody-negative sera (0.2472) was used as the cutoff between anti-gB antibody-positive and -negative results. All sera from 100 anti-CMV IgG-seronegative subjects were negative for antibody to gB. All but 1 of 168 sera from seropositive subjects were positive for antibody to gB. Observed antibody levels based on titration to the endpoint were very similar to results calculated using linear regression. The run-to-run consistency of endpoints was excellent, with 38 runs from one operator and 48 runs from another all giving results within 1 dilution of the mean value for each of three anti-CMV IgG antibody-positive serum pools. The geometric mean titer of antibody to gB for 99 sera from seropositive blood donors was 1/10,937. This ELISA gives accurate and reproducible results for the relative quantity of anti-CMV gB IgG in serum over a wide range of antibody levels.


BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e048142
Author(s):  
Louise J Robertson ◽  
Julie S Moore ◽  
Kevin Blighe ◽  
Kok Yew Ng ◽  
Nigel Quinn ◽  
...  

ObjectiveTo evaluate the dynamics and longevity of the humoral immune response to SARS-CoV-2 infection and assess the performance of professional use of the UK-RTC AbC-19 Rapid Test lateral flow immunoassay (LFIA) for the target condition of SARS-CoV-2 spike protein IgG antibodies.DesignNationwide serological study.SettingNorthern Ireland, UK, May 2020–February 2021.ParticipantsPlasma samples were collected from a diverse cohort of individuals from the general public (n=279), Northern Ireland healthcare workers (n=195), pre-pandemic blood donations and research studies (n=223) and through a convalescent plasma programme (n=183). Plasma donors (n=101) were followed with sequential samples over 11 months post-symptom onset.Main outcome measuresSARS-CoV-2 antibody levels in plasma samples using Roche Elecsys Anti-SARS-CoV-2 IgG/IgA/IgM, Abbott SARS-CoV-2 IgG and EuroImmun IgG SARS-CoV-2 ELISA immunoassays over time. UK-RTC AbC-19 LFIA sensitivity and specificity, estimated using a three-reference standard system to establish a characterised panel of 330 positive and 488 negative SARS-CoV-2 IgG samples.ResultsWe detected persistence of SARS-CoV-2 IgG antibodies for up to 10 months post-infection, across a minimum of two laboratory immunoassays. On the known positive cohort, the UK-RTC AbC-19 LFIA showed a sensitivity of 97.58% (95.28% to 98.95%) and on known negatives, showed specificity of 99.59% (98.53 % to 99.95%).ConclusionsThrough comprehensive analysis of a cohort of pre-pandemic and pandemic individuals, we show detectable levels of IgG antibodies, lasting over 46 weeks when assessed by EuroImmun ELISA, providing insight to antibody levels at later time points post-infection. We show good laboratory validation performance metrics for the AbC-19 rapid test for SARS-CoV-2 spike protein IgG antibody detection in a laboratory-based setting.


2020 ◽  
Vol 8 ◽  
Author(s):  
Kohei Fujita ◽  
Shinpei Kada ◽  
Osamu Kanai ◽  
Hiroaki Hata ◽  
Takao Odagaki ◽  
...  

Background: The coronavirus disease-2019 (COVID-19) pandemic is associated with a heavy burden on the mental and physical health of patients, regional healthcare resources, and global economic activity. While understanding of the incidence and case-fatality rates has increased, there are limited data concerning seroprevalence of antibodies against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in healthcare workers during the pre-pandemic period. This study aimed to quantitatively evaluate seroprevalence of SARS-CoV-2 antibodies in healthcare workers in the southern part of Kyoto city, Japan.Methods: We prospectively recruited healthcare workers from a single hospital between April 10 and April 20, 2020. We collected serum samples from these participants and quantitatively evaluated SARS-CoV-2 IgG antibody levels using enzyme-linked immunosorbent assays.Results: Five (5.4%), 15 (16.3%), and 72 (78.3%) participants showed positive, borderline, and negative serum SARS-CoV-2 IgG antibody status, respectively. We found the mean titer associated with each antibody status (overall, positive, borderline, and negative) was clearly differentiated. Participants working at the otolaryngology department and/or with a history of seasonal common cold symptoms had a significantly higher SARS-CoV-2 IgG antibody titer (p = 0.046, p = 0.046, respectively).Conclusions: Five (5.4%) and 15 (16.3%) participants tested positive and borderline, respectively, for SARS-CoV-2 IgG antibody during the COVID-19 pre-pandemic period. These rates were higher than expected, based on government situation reports. These findings suggest that COVID-19 had already spread within the southern part of Kyoto city at the early stage of the pandemic.


Author(s):  
Sheila F Lumley ◽  
Jia Wei ◽  
Denise O’Donnell ◽  
Nicole E Stoesser ◽  
Philippa C Matthews ◽  
...  

Abstract Background SARS-CoV-2 IgG antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. Methods We present 6 months of data from a longitudinal seroprevalence study of 3276 UK healthcare workers (HCWs). Serial measurements of SARS-CoV-2 anti-nucleocapsid and anti-spike IgG were obtained. Interval censored survival analysis was used to investigate the duration of detectable responses. Additionally, Bayesian mixed linear models were used to investigate anti-nucleocapsid waning. Results Anti-spike IgG levels remained stably detected after a positive result, e.g., in 94% (95% credibility interval, CrI, 91-96%) of HCWs at 180 days. Anti-nucleocapsid IgG levels rose to a peak at 24 (95% credibility interval, CrI 19-31) days post first PCR-positive test, before beginning to fall. Considering 452 anti-nucleocapsid seropositive HCWs over a median of 121 days from their maximum positive IgG titre, the mean estimated antibody half-life was 85 (95%CrI, 81-90) days. Higher maximum observed anti-nucleocapsid titres were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity and prior self-reported symptoms were independently associated with higher maximum anti-nucleocapsid levels and increasing age and a positive PCR test undertaken for symptoms with longer anti-nucleocapsid half-lives. Conclusion SARS-CoV-2 anti-nucleocapsid antibodies wane within months, and faster in younger adults and those without symptoms. However, anti-spike IgG remains stably detected. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.


2021 ◽  
pp. annrheumdis-2021-220647
Author(s):  
Victoria Furer ◽  
Tali Eviatar ◽  
Devy Zisman ◽  
Hagit Peleg ◽  
Daphna Paran ◽  
...  

IntroductionVaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.MethodsA multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2–6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose.ResultsFollowing vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients.ConclusionmRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.


Author(s):  
Kohei Fujita ◽  
Shinpei Kada ◽  
Osamu Kanai ◽  
Hiroaki Hata ◽  
Takao Odagaki ◽  
...  

Background: The coronavirus disease-2019 (COVID-19) pandemic is associated with a heavy burden on the mental and physical health of patients, regional healthcare resources, and global economic activity. While our understanding of the incidence and case-fatality rates increases, data on seroprevalence of antibodies against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in healthcare workers during the peri-pandemic period is insufficient. This study quantitatively evaluated seroprevalence of SARS-CoV-2 antibody in healthcare workers in the southern part of Kyoto city, Japan. Methods: We prospectively recruited healthcare workers from a single hospital between April 10 and April 20, 2020. We collected serum samples from these participants and quantitatively evaluated SARS-CoV-2 IgG antibody levels by enzyme-linked immunosorbent assay. Results: Five (5.4%), 15 (16.3%), and 72 (78.3%) participants showed positive, borderline, and negative serum SARS-CoV-2 IgG antibody status, respectively. We found the mean titer associated with each antibody status (overall, positive, borderline, and negative) was clearly differentiated. Participants working at the otolaryngology department and/or having a history of seasonal common cold symptoms had a significantly higher titer of SARS-CoV-2 IgG antibody (p=0.046, p=0.046, respectively). Conclusions: Five (5.4%) and 15 (16.3%) participants tested positive and borderline, respectively, for SARS-CoV-2 IgG antibody during the COVID-19 peri-pandemic period. These rates were higher than expected based on government situation reports. The present findings suggest that COVID-19 was already spread in the southern part of Kyoto city at the early stage of pandemic.


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