Total anti-SARS-CoV-2 antibodies measured 6 months after Pfizer-BioNTech COVID-19 vaccination in healthcare workers

Background: This study aimed at monitoring the kinetics of serum total anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antibodies in a cohort of healthcare workers after voluntary vaccination with Pfizer-BioNTech coronavirus disease 2019 (COVID-19).Methods: The study population consisted of 787 healthcare workers (mean age 44±12 years; 66% females), who received two 30 μg doses of Pfizer-BioNTech COVID-19 vaccine, 3 weeks apart. Venous blood was drawn before the first vaccine dose, immediately before the second vaccine dose, and then at 1, 3 and 6 months after the second vaccine dose. Serological testing employed the total anti-SARS-CoV-2 antibodies measurement with Roche Elecsys Anti-SARS-CoV-2 S chemiluminescent immunoassay.Results: The median serum levels of total anti-SARS-CoV-2 antibodies reached the peak (1762 KU/L) 1 month after the second vaccine dose, but tended to progressively decline at the 3-month (1086 KU/L) and 6-month (802 KU/L) follow-up points. Overall, the values after 3- and 6-months were 37% and 57% lower than the corresponding concentrations measured at the peak. No healthcare worker had total anti-SARS-CoV-2 antibodies below the method-dependent cut-off. The decline compared to the peak was more accentuated in baseline seropositive persons than in those who were baseline seronegative (74% vs. 52%) cohort. The 6-month post-vaccination anti-SARS-CoV-2 antibodies in subjects aged <65 years remained over 2-fold higher than that measured in those aged ≥65 years (813 vs. 343 KU/L). Conclusions: Gradual decline of total anti-SARS-CoV-2 antibodies occurred 6 months after Pfizer-BioNTech COVID-19 vaccination, though values remained higher than the method-dependent cut-off, with no case of seronegativization.

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Anti-spike S1 IgA, anti-spike trimeric IgG, and anti-spike RBD IgG response after BNT162b2 COVID-19 mRNA vaccination in healthcare workers

Journal of Medical Biochemistry ◽

10.5937/jomb0-32373 ◽

2021 ◽

Author(s):

Gian Luca Salvagno ◽

Brandon Henry ◽

Giovanni Di Piazza ◽

Laura Pighi ◽

Simone De Nitto ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Healthcare Workers ◽

Vaccine Dose ◽

Serum Levels ◽

Cell Mediated Immunity ◽

Inverse Association ◽

Serum Samples ◽

Serum Igg ◽

Study Population

Background: Most studies on immune response after coronavirus disease 2019 (COVID-19) vaccination focused on serum IgG antibodies and cell-mediated immunity, discounting the role of anti-SARS-CoV-2 neutralizing IgA antibodies in preventing viral infection. This study was aimed to quantify serum IgG and IgA neutralizing antibodies after mRNA COVID-19 vaccination in baseline SARS-CoV-2 seronegative healthcare workers. Methods: The study population consisted of 181 SARS-CoV-2 seronegative healthcare workers (median age 42 years, 59.7% women), receiving two doses of Pfizer COVID-19 vaccine BNT162b2. Serum samples were collected before receiving the first vaccine dose, 21 days (before the second vaccine dose) and 50 days afterwards. We then measured anti-spike trimeric IgG (Liaison XL, DiaSorin), anti-spike receptor binding domain (RBD) IgG (Access 2, Beckman Coulter) and anti-spike S1 subunit IgA (ELISA, Euroimmun). Results were presented as median and interquartile range (IQR). Results: Vaccine administration elicited all anti-SARS-CoV-2 antibodies measured. Thirty days after the second vaccine dose, 100% positivization occurred for anti-spike trimeric IgG and anti-spike RBD IgG, whilst 1.7% subjects remained anti-spike S1 IgA negative. The overall increase of antibodies level over baseline after the second vaccine dose was 576.1 (IQR, 360.7-867.8) for anti-spike trimeric IgG, 1426.0 (IQR, 742.0-2698.6) for anti-spike RBD IgG, and 20.2 (IQR, 12.5-32.1) for anti-spike S1 IgA. Significant inverse association was found between age and overall increase of anti-spike trimeric IgG (r=-0.24; p=0.001) and anti-spike S1 IgA (r=-0.16; p=0.028), but not with anti-spike RBD IgG (r=-0.05; p=0.497). Conclusions: mRNA COVID-19 vaccination elicits sustained serum levels serum anti-spike trimeric IgG and anti-spike RBD IgG, while also modestly but significantly increasing those of serum anti-spike S1 IgA.

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Human IgG and IgA responses to COVID-19 mRNA vaccines

10.1101/2021.03.23.21254060 ◽

2021 ◽

Author(s):

Julian Campillo Luna ◽

Adam V Wisnewski ◽

Carrie A Redlich

Keyword(s):

Vaccine Dose ◽

Serum Levels ◽

Rapid Decline ◽

Natural Immunity ◽

Limited Information ◽

Viral Neutralization ◽

Time To Peak ◽

Specific Igg ◽

Kinetics Of

SARS-CoV-2 spike antigen-specific IgG and IgA elicited by infection mediate viral neutralization and are likely an important component of natural immunity, however, limited information exists on vaccine induced responses. We measured COVID-19 mRNA vaccine induced IgG and IgA in serum serially, up to 80 days post vaccination in 4 subjects. Spike antigen-specific IgG levels rose exponentially and plateaued 21 days after the initial vaccine dose. After the second vaccine dose IgG levels increased further, reaching a maximum approximately 7-10 days later, and remained elevated (average of 78% peak levels) during the additional 20-50 day follow up period. COVID-19 mRNA vaccination elicited spike antigen-specific IgA with similar kinetics of induction and time to peak levels, but more rapid decline in serum levels following both the 1st and 2nd vaccine doses (<23% peak levels within 80 days of the initial shot). The data demonstrate COVID-19 mRNA vaccines effectively induce spike antigen specific IgG and IgA and highlight marked differences in their persistence in serum.

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Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

10.1101/2021.03.19.21253989 ◽

2021 ◽

Author(s):

Elisa Danese ◽

Martina Montagnana ◽

Gian Luca Salvagno ◽

Matteo Gelati ◽

Denise Peserico ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Protein Concentration ◽

Venous Blood ◽

Case Series ◽

Vaccine Dose ◽

Humoral Response ◽

Post Vaccination ◽

Humoral Immune

Background. Since universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response. Methods. Three healthcare workers received 30 μg BNT162b2 mRNA Covid-19 Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), IgG anti-S1/S2, IgG anti-RBD, IgM anti-RBD, IgM anti-N/S1 and IgA anti-S1. Results. All subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, IgG anti-S1/S2 and IgG anti-RBD levels increased between 91-368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by ~30-, ~8- and ~8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing ~50 days after the first dose. IgA anti-S1 levels increased between 7-11 days after the first dose, slightly declined before the second dose, after which levels augmented by ~24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4 to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all time points. Conclusions. BNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving IgG and IgA, magnified by the second vaccine dose.

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Human IgG and IgA responses to COVID-19 mRNA vaccines

PLoS ONE ◽

10.1371/journal.pone.0249499 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0249499

Author(s):

Adam V. Wisnewski ◽

Julian Campillo Luna ◽

Carrie A. Redlich

Keyword(s):

Vaccine Dose ◽

Serum Levels ◽

Rapid Decline ◽

Natural Immunity ◽

Limited Information ◽

Viral Neutralization ◽

Time To Peak ◽

Specific Igg ◽

Kinetics Of

SARS-CoV-2 spike antigen-specific IgG and IgA elicited by infection mediate viral neutralization and are likely an important component of natural immunity, however, limited information exists on vaccine induced responses. We measured COVID-19 mRNA vaccine induced IgG and IgA in serum serially, up to 145 days post vaccination in 4 subjects. Spike antigen-specific IgG levels rose exponentially and plateaued 21 days after the initial vaccine dose. After the second vaccine dose IgG levels increased further, reaching a maximum approximately 7–10 days later, and remained elevated (average of 58% peak levels) during the additional >100 day follow up period. COVID-19 mRNA vaccination elicited spike antigen-specific IgA with similar kinetics of induction and time to peak levels, but more rapid decline in serum levels following both the 1st and 2nd vaccine doses (<18% peak levels within 100 days of the 2nd shot). The data demonstrate COVID-19 mRNA vaccines effectively induce spike antigen specific IgG and IgA and highlight marked differences in their persistence in serum.

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Assessment of Post-Vaccination Antibody Response Eight Months after the Administration of BNT1622b2 Vaccine to Healthcare Workers with Particular Emphasis on the Impact of Previous COVID-19 Infection

Vaccines ◽

10.3390/vaccines9121508 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1508

Author(s):

Blanka Wolszczak-Biedrzycka ◽

Anna Bieńkowska ◽

Justyna Dorf

Keyword(s):

Healthcare Workers ◽

Venous Blood ◽

Vaccine Dose ◽

Post Vaccination ◽

Vaccination Programs ◽

Humoral Immune ◽

History Of ◽

Antibody Titers ◽

Antibody Levels ◽

The Impact

At the end of 2020, COVID-19 vaccination programs were initiated in many countries, including Poland. The first vaccine approved in Poland was the BNT162b2 mRNA preparation (Pfizer/BioNTech), and the first vaccinated group were healthcare workers. The aim of the present study was to evaluate post-vaccine antibody titers 8 months after the second vaccine dose had been administered to a group of employees of the Hospital of the Ministry of the Interior and Administration in Olsztyn (Poland). The employees were divided into two groups: persons who had COVID-19 in the fourth quarter of 2020 and were vaccinated in January–February 2021, and persons without a history of COVID-19 who were vaccinated during the same period. The analyzed material was venous blood serum collected from 100 hospital employees on 23–28 September 2021. The level of anti-SARS-CoV-2 S antibodies was measured with a Roche Cobas e411 analyzer using the electrochemiluminescence (ECLIA) method. The study demonstrated that persons with a history of SARS-CoV-2 infection had significantly higher antibody levels (taking into account gender, age, type of work performed, and severity of post-vaccination symptoms) than employees without a history of COVID-19. The study also revealed that the type of work, age, gender, and the course of SARS-CoV-2 infection can influence the humoral immune response. The presented results may prove helpful in the context of administering additional vaccine doses.

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Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0339 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Elisa Danese ◽

Martina Montagnana ◽

Gian Luca Salvagno ◽

Denise Peserico ◽

Laura Pighi ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Protein Concentration ◽

Venous Blood ◽

Case Series ◽

Vaccine Dose ◽

Humoral Response ◽

Post Vaccination ◽

Humoral Immune

Abstract Objectives Since universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response. Methods Three healthcare workers received 30 μg BNT162b2 mRNA Covid-19 Pfizer Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), anti-S1/S2 and anti-RBD IgG, anti-RBD and anti-N/S1 IgM, and anti-S1 IgA. Results All subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG levels increased between 91 and 368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by ∼30-, ∼8- and ∼8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing ∼50 days after the first vaccine dose. Anti-S1 IgA levels increased between 7 and 11 days after the first dose, slightly declined before the second dose, after which levels augmented by ∼24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4- to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all-time points. Conclusions BNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving anti-SARS-Cov-2 IgG and IgA, magnified by the second vaccine dose.

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Compliance among infants exposed to hepatitis B virus in a post-vaccination serological testing program in four provinces in China

Infectious Diseases of Poverty ◽

10.1186/s40249-019-0568-y ◽

2019 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Hui Zheng ◽

Guo-Min Zhang ◽

Po-Lin Chan ◽

Fu-Zhen Wang ◽

Lance Everett Rodewald ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Venous Blood ◽

Serological Testing ◽

Sample Collection ◽

Post Vaccination ◽

Loss To Follow Up ◽

Factors Associated ◽

B Virus

Abstract Background Mother to child transmission of hepatitis B virus (HBV) remains the most common form of HBV infection in China. Prevention of HBV vertical transmission involves timely administration of the complete hepatitis B vaccine (HepB) series and hepatitis B immunoglobulin. Post-vaccination serological testing (PVST) is utilized to determine an infant’s outcome after HBV exposure and completion of HepB series. We aim to determine the frequency of compliance with a PVST testing cascade for HBV infected mothers and analyze factors associated with infant lost to follow up (LTFU). Methods We conducted a retrospective cohort review of previously collected data in Fujian, Jiangxi, Zhejiang and Chongqing provinces in China from 1 June 2016–31 December 2017. The study population included all HBV-exposed infants and their mothers. SAS software was used for statistical analyses. Bivariate and multivariate regression analyses (presented in odds ratio [OR] with 95% confidence intervals [CI]) were used to compare the proportional differences of factors associated with PVST not being completed. Results Among enrolled 8474 target infants, 40% of them transferred out of the study provinces without further information and 4988 were eligible for PVST. We found 20% (994) of infants were not compliant with the testing cascade: 55% of LTFU occurred because parents refused venous blood sample collection or failure of sample collection in the field, 16% transferred out after 6 months of age, and 10% of families chose to have independent, confidential PVST completed without reporting results. High PVST noncompliance rates were more likely to be from Fujian (aOR = 17.0, 95% CI: 9.7–29.9), Zhejiang (aOR = 5.7, 95% CI: 3.2–10.1) and Jiangxi (aOR = 1.9, 95% CI: 1.0–3.4), and from HBV e antigen positive mother (aOR = 1.2, 95% CI: 1.1–1.4). Conclusions This study found that the LTFU rate reached 20% in PVST program, which was a significant problem. We recommend implementing a national electronic information system for tracking HBV at risk mother-infant pairs; encourage further research in developing a less invasive means of completing PVST, and take effective measures nationally to reduce HBV stigma. Without reducing the loss to follow up rate among infants eligible for PVST, elimination of vertical HBV transmission will be impossible.

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Kinetics of epsilon antitoxin antibodies in different strategies for active immunization of lambs against enterotoxaemia

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2013000800005 ◽

2013 ◽

Vol 33 (8) ◽

pp. 979-982

Author(s):

Heni F. Costa ◽

Selene D. Babboni ◽

Carlos F.C. Rodrigues ◽

Carlos R. Padovani ◽

Iveraldo S. Dutra ◽

...

Keyword(s):

Indirect Elisa ◽

Small Ruminants ◽

Vaccine Dose ◽

Humoral Response ◽

Active Immunization ◽

Common Disease ◽

Post Vaccination ◽

Type D ◽

Epsilon Toxin ◽

Kinetics Of

Enterotoxaemia, a common disease that affects domestic small ruminants, is mainly caused by the epsilon toxin of Clostridium perfringens type D. The present study tested four distinct immunization protocols to evaluate humoral response in lambs, a progeny of non-vaccinated sheep during gestation. Twenty-four lambs were randomly allocated into four groups according to age (7, 15, 30 and 45 days), receiving the first dose of epsilon toxoid commercial vaccine against clostridiosis with booster after 30 days post vaccination. Indirect ELISA was performed after the first vaccine dose and booster to evaluate the immune response of the lambs. Results showed that for the four protocols tested all lambs presented serum title considered protective (≥0.2UI/ml epsilon antitoxin antibodies) and also showed that the anticipation of primovaccination of lambs against enterotoxaemia conferred serum title considered protective allowing the optimization of mass vaccination of lambs.

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Impact of Age and Sex on Antibody Response Following the Second Dose of COVID-19 BNT162b2 mRNA Vaccine in Greek Healthcare Workers

Microorganisms ◽

10.3390/microorganisms9081725 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1725

Author(s):

Niki Vassilaki ◽

Antonios N. Gargalionis ◽

Anastasia Bletsa ◽

Nikolaos Papamichalopoulos ◽

Elisavet Kontou ◽

...

Keyword(s):

Healthcare Workers ◽

Venous Blood ◽

Age Groups ◽

Vaccine Dose ◽

Humoral Response ◽

Continuous Variables ◽

Igg Antibody ◽

Female Population ◽

Significant Difference ◽

Antibody Titers

Anti-SARS-CoV-2 spike RBD (receptor-binding domain) IgG antibody levels were monitored in 1643 volunteer healthcare workers of Eginition, Evangelismos, and Konstantopoulio General Hospitals (Athens, Greece), who underwent vaccination with two doses of COVID-19 BNT162b2 mRNA vaccine (Pfizer) and had no history of SARS-CoV-2 infection. Venous blood was collected 20–30 days after the second vaccine dose and anti-RBD IgG levels were determined using CMIA SARS-CoV-2 IgG II Quant (Abbott) on ARCHITECT i System or ADVIA Centaur SARS-CoV-2 IgG (Siemens) on Centaur XP platform. From the total population of 1643 vaccinees (533 M/1110 F; median age = 49; interquartile range-IQR = 40–56), 1636 (99.6%) had anti-SARS-CoV-2 IgG titers above the positivity threshold of the assay used. One-Way ANOVA Kruskal-Wallis H test showed a statistically significant difference in the median of antibody titers between the different age groups (p < 0.0001). Consistently, Spearman’s correlation coefficient (r) for IgGs and age as continuous variables was −0.2380 (p = 1.98 × 10−17). Moreover, antibody titers were slightly higher by 1.2-mean fold (p = 3 × 10−6) in the total female population of the three hospitals (median = 1594; IQR = 875–2584) as compared to males (median = 1292; IQR = 671.9–2188). The present study supports that BNT162b2 vaccine is particularly effective in producing high anti-SARS-CoV-2 IgG levels in healthy individuals, and this humoral response is age- and gender-dependent.

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Abstract 828: Serum Midkine Predicts Cardiac Events in Chronic Heart Failure Patients

Circulation ◽

10.1161/circ.118.suppl_18.s_620 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Tatsuro Kitahara ◽

Yasuchika Takeishi ◽

Tetsuro Shishido ◽

Tetsu Watanabe ◽

Joji Nitoube ◽

...

Keyword(s):

Heart Failure ◽

Hazard Analysis ◽

Inflammatory Cells ◽

Serum Levels ◽

Functional Class ◽

Heparin Binding ◽

Cardiac Events ◽

Apoptotic Effect ◽

Study Population

Midkine (MK), a heparin-binding growth factor, has various functions such as migration of inflammatory cell and anti-apoptotic effect. Invasion of inflammatory cells and cardiomyocyte apoptosis are involved in development and progression of heart failure (HF). However, relationship between MK and HF has not been previously examined. Therefore, we examined clinical significance of serum MK levels to determine the prognosis of HF patients. Serum levels of MK were measured at admission in 216 consecutive patients hospitalized for chronic HF and 60 control subjects. Patients were prospectively followed during a median follow-up period of 658 days with the end points of cardiac death and progressive HF requiring re-hospitalization. Serum concentrations of MK were significantly higher in patients with HF than in controls and increased as NYHA functional class rose (fig 1 ). There were 74 cardiac events, including 30 cardiac deaths and 44 re-hospitalization for HF during follow-up period. Patients with cardiac events had significantly higher concentrations of MK than those without cardiac events (539 ± 57 pg/ml vs. 331 ± 17 pg/ml, P < 0.01). Patients were divided into 4 groups based on midkine levels. Risk of cardiac events increased as MK levels rose (fig 2 ). In addition, the Cox multivariate hazard analysis showed that MK was an independent predictor of cardiac events (hazard ratio 1.280, 95% CI 1.027–1.578, P<0.05). Serum MK level is increased in HF patients, and MK is a novel marker for risk stratifying chronic HF patients. Figure 1. Serum Midkine Levels in Study Population Figure 2. Quartile Analysis of Serum Midkine Levels and Relative Risk for All Cardiac Events

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