Antibody Response after BNT162b2 Vaccination in Healthcare Workers Previously Exposed and Not Exposed to SARS-CoV-2

The Pfizer/BioNtech Comirnaty vaccine (BNT162b2 mRNA COVID-19) against SARS-CoV-2 is currently in use in Italy. Antibodies to evaluate SARS-CoV-2 infection prior to administration are not routinely tested; therefore, two doses may be administered to asymptomatic previously exposed subjects. The aim of this study is to assess if any difference in antibody concentration between subjects exposed and not exposed to SARS-CoV-2 prior to BNT162b2 was present after the first dose and after the second dose of vaccine. Data were retrospectively collected from the clinical documentation of 337 healthcare workers who underwent SARS-CoV-2 testing before and after BNT162b2. Total anti RBD (receptor-binding domain) antibodies against SARS-CoV-2′s spike protein were measured before and 21 days after the first dose, and 12 days after the second dose of BNT162b2. Twenty-one days after the first dose, there was a statistically significant difference in antibody concentration between the two groups, which was also maintained twelve days after the second dose. In conclusion, antibody response after receiving BNT162b2 is greater in subjects who have been previously exposed to SARS-CoV-2 than in subjects who have not been previously exposed to the virus, both after 21 days after the first dose and after 12 days from the second dose. Antibody levels, 21 days after the first dose, reached a titer considered positive by the test manufacturer in the majority of subjects who have been previously infected with SARS-CoV-2. Evaluating previous infection prior to vaccination in order to give the least effective number of doses should be considered.

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Investigating Adherence to COVID-19 Vaccination and Serum Antibody Concentration among Hospital Workers—The Experience of an Italian Private Hospital

Vaccines ◽

10.3390/vaccines9111332 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1332

Author(s):

Guglielmo Forgeschi ◽

Giuseppe Cavallo ◽

Chiara Lorini ◽

Fiamma Balboni ◽

Francesca Sequi ◽

...

Keyword(s):

Healthcare Workers ◽

Private Hospital ◽

Serum Antibody ◽

Hospital Staff ◽

Antibody Concentration ◽

Hospital Workers ◽

A Value ◽

Previous Infection ◽

Duration Of Protection ◽

Antibody Levels

SARS-CoV-2 transmission has been high, especially among healthcare workers worldwide during the first wave. Vaccination is recognized as the most effective approach to combat the pandemic, but hesitation to get vaccinated represents an obstacle. Another important issue is the duration of protection after administration of the full vaccination cycle. Based on these premises, we conducted a study to evaluate vaccination adherence and the anti-S antibodies levels among hospital workers, from January to March, 2021. To assess adherence, an anonymous questionnaire was used. Anti-S antibody levels were obtained from the monitoring serological sample database. In total, 56.2% of the unvaccinated people did not report a previous infection from COVID-19. Among those who have not been vaccinated, 12.5% showed distrust against the vaccine, 8.3% stated to have received contraindications to the vaccination, and 6.3% did not report any choice. Analyzing anti-S antibody levels, only one person was found to have a value below the lower cut-off, two weeks, and three months after receiving their second dose. One was below the cut-off after two weeks, and then above the same cut-off after three months. The results of our survey should be seen as a stimulus to further sensitize hospital staff to the importance of vaccination and pay attention to anti-S antibody levels monitoring.

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SARS-CoV-2 virus masking of RBD epitopes; unmasking and cross-reactivity induced by mRNA vaccines

10.21203/rs.3.rs-591752/v1 ◽

2021 ◽

Author(s):

Rafael Ramiro de Assis ◽

Aarti Jain ◽

Rie Nakajima ◽

Algis Jasinskas ◽

Saahir Kahn ◽

...

Keyword(s):

Nucleocapsid Protein ◽

Healthcare Workers ◽

Orange County ◽

Medical Center ◽

Vaccination Campaign ◽

Cross Reactivity ◽

Receptor Binding Domain ◽

Before And After ◽

Blood Specimens ◽

Finger Stick

Abstract We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8,476 finger stick blood specimens were collected before and after an aggressive mRNA vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing 10 SARS-CoV-2 antigens, 4 SARS, 3 MERS, 12 Common CoV, and 8 Influenza antigens. Twenty-six percent of 3,347 specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive. The Ab response was predominantly against nucleocapsid (NP), full length spike and the spike S2 domain. Anti-receptor binding domain (RBD) reactivity was low and there was no cross-reactivity against SARS S1 or SARS RBD. An aggressive mRNA vaccination campaign at the UCI Medical Center started on December 16, 2020 and 6,724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% in December to 79% in January, 93% in February and 99% in March. mRNA vaccination induced much higher Ab levels especially against the RBD domain and significant cross-reactivity against SARS RBD and S1 was also observed. Nucleocapsid protein Abs can be used to distinguish individuals in a population of vaccinees to classify those who have been previously infected and those who have not, because nucleocapsid is not in the vaccine. Previously infected individuals developed higher Ab titers to the vaccine than those who have not been previously exposed. These results indicate that mRNA vaccination rapidly induces a much stronger and broader Ab response than SARS-CoV-2 infection.

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Effect Monitoring and Insights from Vaccination program of Healthcare Workforce from a tertiary level hospital in India against SARS-CoV-2

10.1101/2021.02.28.21252621 ◽

2021 ◽

Author(s):

Rajat Ujjainia ◽

Akansha Tyagi ◽

Viren Sardana ◽

Salwa Naushin ◽

Nitin Bhatheja ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Protein S ◽

Maximum Increase ◽

Post Vaccination ◽

Neutralizing Activity ◽

Effect Monitoring ◽

Antibody Levels ◽

Level Hospital

AbstractThe Oxford-Astra Zeneca COVID 19 vaccine (AZD1222 or ChAdOx1) is locally manufactured as Covishield by Serum Institute, Pune, India. In a group of 307 healthcare workers administered Covishield, we report measured antibody response to SARS-CoV-2 directed against the spike protein (S-antigen) at days 0, 7, 14, 28 and 45, with second dose on day 28 for all except 20 subjects who did not receive a second dose. In 129 subjects (42%) who had already developed antibodies to SARS-CoV-2 at day 0 (before immunization), it was observed that antibody response was significantly higher at each time point, with the maximum increase seen between days 0 and 7. The antibody levels and neutralizing activity in these subjects had peaked by day 28 and the second dose did not lead to further increase. Data from 9 subjects who were seropositive at baseline and received only one dose was similar to those who received both doses. In contrast the baseline sero-negative group (n=178) started developing antibody response only after 14 days or later. Administration of the second dose was associated with further increase in antibody levels at day 45 compared to day 28, with marked increase in neutralizing activity. In baseline seronegative subjects, who did not take the vaccine at day 28 (n=11), the antibody levels increased by about 2.5 folds between days 28 and 45, with minimal change in the neutralizing antibodies. In general, vaccination was well tolerated, and there were no group specific differences in post-vaccination symptomatology. Our data suggests that ChAdOx1 is highly immunogenic, particularly so where previous SARS CoV2 antibody-response is established. In such subjects, a single dose may be sufficient but in absence of such determination, both doses are required.

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Can individuals with low antibody responses to vaccines against other viruses acquire adequate SARS-CoV-2 antibody after vaccination with the BNT162b2 mRNA vaccine?

10.1101/2021.12.26.21268358 ◽

2021 ◽

Author(s):

Wataru Ogura ◽

Kouki Ohtsuka ◽

Sachiko Matsuura ◽

Takahiro Okuyama ◽

Satsuki Matsushima ◽

...

Keyword(s):

Cohort Study ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Antibody Activity ◽

Low Responders ◽

Before And After ◽

Positive Threshold ◽

Antibody Levels

Objective In Japan, healthcare workers (HCWs) are vaccinated against coronavirus disease (COVID-19) and other contagious viruses (measles, rubella, chickenpox, mumps, and hepatitis B) to prevent nosocomial infection. However, some do not produce sufficient antibodies after vaccination (low responders). This study investigated changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels among HCWs after SARS-CoV-2 vaccination and assessed whether low responders produced adequate SARS-CoV-2 anti-spike and neutralizing antibodies. Methods We conducted a prospective cohort study of HCWs before and after vaccination with the BNT162b2 mRNA vaccine in a hospital in Tokyo, Japan. The HCWs received two doses of BNT162b2 vaccine, 3 weeks apart. Those whose antibody levels against previous antiviral vaccines did not reach protective antibody levels after receiving two doses were defined as low responders, whereas those who produced adequate antibodies were defined as normal responders. SARS-CoV-2 anti-spike antibodies were measured 11 times from before the first BNT162b2 vaccination to 5 months after the second vaccination. SARS-CoV-2 neutralizing antibody activity was measured twice in low responders, 1 week to 1 month and 5 months after the second vaccination. Results Fifty HCWs were included in the analytic cohort. After vaccination, SARS-CoV-2 anti-spike antibody was detectable in the samples from both responders at each timepoint, but the level was lower at 5 months than at 1 week after the second vaccination. Low responders had SARS-CoV-2 neutralizing antibody activity 1 week to 1 month after the second vaccination, which exceeded the positive threshold after 5 months. Conclusion After BNT162b2 vaccination, low responders acquired adequate SARS-CoV-2 anti-spike and SARS-CoV-2 neutralizing antibodies to prevent SARS-CoV-2. However, SARS-CoV-2 anti-spike antibody levels were lower at 5 months than at 1 week after the second dose of BNT162b2 vaccine in low and normal responders. Therefore, low responders should also receive a third dose of BNT162b2 vaccine.

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Serum Antibody Response Comparison and Adverse Reaction Analysis in Healthcare Workers Vaccinated with the BNT162b2 or ChAdOx1 COVID-19 Vaccine

Vaccines ◽

10.3390/vaccines9121379 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1379

Author(s):

Sung-Hee Lim ◽

Seong-Hyeok Choi ◽

Bora Kim ◽

Ji-Youn Kim ◽

Young-Sok Ji ◽

...

Keyword(s):

Adverse Events ◽

Antibody Response ◽

Healthcare Workers ◽

Serum Antibody ◽

Neutralizing Antibody ◽

And Gender ◽

Gender Categories ◽

Antibody Levels ◽

Very High

The COVID-19 pandemic is changing rapidly and requires different strategies to maintain immunization. In Korea, different COVID-19 vaccines are recommended and available for various populations, including healthcare workers (HCWs) at high risk of SARS-CoV-2 infection. We plan to evaluate the adverse events (AEs) and immunogenicity of the BNT162b2 and ChAdOx1 vaccines in HCWs at a single center. This cohort study included HCWs fully vaccinated with either BNT162b2 or ChAdOx1. Blood samples were taken eight weeks after the second vaccination with both COVID-19 vaccines and six months after the second vaccination from participants with the BNT162b2 vaccine. The primary endpoint for immunogenicity was the serum neutralizing antibody responses eight weeks after vaccination. The secondary endpoint was the incidence of various AEs within 28 days of each vaccination. Between 16 March and 23 June 2021, 115 participants were enrolled (65 in the ChAdOx1 group and 50 in the BNT162b2 group). Significantly higher surrogate virus neutralization test (sVNT) inhibition was observed in participants vaccinated with two doses of BNT162b2 (mean (SD) 91.4 (9.68)%) than in those vaccinated with ChAdOx1 (mean (SD) 73.3 (22.57)%). The effectiveness of the BNT162b2 vaccine was maintained across all age and gender categories. At six months after the second dose, serum antibody levels declined significantly in the BNT162b2 group. The main adverse events, including fever, myalgia, fatigue, and headache, were significantly higher in the ChAdOx1 group after the first dose, whereas, after the second dose, those AEs were significantly higher in the BNT162b2 group (p < 0.05). Two doses of either the ChAdOx1 or the BNT162b2 COVID-19 vaccine resulted in very high seropositivity among the HCWs at our center. The quality of the antibody response, measured by sVNT inhibition, was significantly better with the BNT162b2 vaccine than with the ChAdOx1 vaccine. There was no significant association between neutralizing antibody response and AE after each vaccination in our cohort.

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Neutralising reactivity against SARS-CoV-2 B.1.617.2 (Delta) variant by vaccination status and pre-exposure

10.21203/rs.3.rs-1131280/v1 ◽

2021 ◽

Author(s):

Enrico Lavezzo ◽

Monia Pacenti ◽

Laura Manuto ◽

Caterina Boldrin ◽

Margherita Cattai ◽

...

Keyword(s):

Antibody Response ◽

Post Infection ◽

Healthcare Workers ◽

Natural Infection ◽

Vaccination Status ◽

Control Groups ◽

Post Exposure ◽

The Third ◽

Antibody Levels

Abstract In February and March 2020, one of the first Italian clusters of SARS-CoV-2 infection was detected in the municipality of Vo’. Positive subjects were followed up at 2 and 9 months post-infection with different immuno-assays and a micro-neutralisation test. Here we report on the results of the third serosurvey conducted in the same population in June 2021, 15 months post-infection, when we tested 61% of the infected individuals (n=76). Antibodies against the spike (S) antigen significantly decreased (P<0.006, Kruskal-Wallis test) among unvaccinated subjects (n=35) and increased (P<0.0001) in vaccinated individuals (n=41), whereas those against the nucleocapsid (N) decreased in the whole cohort. From the comparison with two control groups (naïve Vo’ inhabitants (n=20) and healthcare workers (HCW, n=61)), subjects vaccinated post exposure (hybrid immunity) had higher antibody levels (P<0.0001) than subjects vaccinated when naïve. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P<0.0001). Finally, the neutralising reactivity of sera against the B.1.617.2 (Delta) was lower than compared to the B.1 strain (median 1:320 versus 1:1280 1/dil, P<0.0001, and 1:640 versus 1:2560 1/dil, P=0.0014, after one or two vaccine doses, respectively), although subjects with hybrid immunity maintained neutralising titres above 1:40 1/dil.

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High titers of multiple antibody isotypes against the SARS-CoV-2 spike receptor-binding domain and nucleoprotein associate with better neutralization

10.1101/2020.08.15.252353 ◽

2020 ◽

Author(s):

Maria G. Noval ◽

Maria E. Kaczmarek ◽

Akiko Koide ◽

Bruno A. Rodriguez-Rodriguez ◽

Ping Louie ◽

...

Keyword(s):

Antibody Response ◽

Receptor Binding ◽

Healthcare Workers ◽

Neutralizing Antibody ◽

Binding Domain ◽

Pseudotyped Virus ◽

Receptor Binding Domain ◽

Neutralization Capacity ◽

Antibody Isotypes ◽

Antibody Titers

AbstractUnderstanding antibody responses to SARS-CoV-2 is indispensable for the development of containment measures to overcome the current COVID-19 pandemic. Here, we determine the ability of sera from 101 recovered healthcare workers to neutralize both authentic SARS-CoV-2 and SARS-CoV-2 pseudotyped virus and address their antibody titers against SARS-CoV-2 nucleoprotein and spike receptor-binding domain. Interestingly, the majority of individuals have low neutralization capacity and only 6% of the healthcare workers showed high neutralizing titers against both authentic SARS-CoV-2 virus and the pseudotyped virus. We found the antibody response to SARS-CoV-2 infection generates antigen-specific isotypes as well as a diverse combination of antibody isotypes, with high titers of IgG, IgM and IgA against both antigens correlating with neutralization capacity. Importantly, we found that neutralization correlated with antibody titers as quantified by ELISA. This suggests that an ELISA assay can be used to determine seroneutralization potential. Altogether, our work provides a snapshot of the SARS-CoV-2 neutralizing antibody response in recovered healthcare workers and provides evidence that possessing multiple antibody isotypes may play an important role in SARS-CoV-2 neutralization.

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Antibody responses to BNT162b2 vaccination in Japan: Monitoring vaccine efficacy by measuring IgG antibodies against the receptor binding domain of SARS-CoV-2

10.1101/2021.07.19.21260728 ◽

2021 ◽

Author(s):

Hidetsugu Fujigaki ◽

Yasuko Yamamoto ◽

Takenao Koseki ◽

Sumi Banno ◽

Tatsuya Ando ◽

...

Keyword(s):

Receptor Binding ◽

Vaccine Efficacy ◽

Vaccination Strategy ◽

Binding Domain ◽

Enzyme Linked Immunosorbent Assay ◽

Receptor Binding Domain ◽

Neutralizing Activity ◽

Before And After ◽

Reliable Performance ◽

Antibody Levels

BACKGROUND: To fight severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), mass vaccination has begun in many countries. To investigate the usefulness of a serological assay to predict vaccine efficacy, we analyzed the levels of IgG, IgM, and IgA against the receptor binding domain (RBD) of SARS-CoV-2 in the sera from BNT162b2 vaccinated individuals in Japan. METHODS: This study included 219 individuals who received two doses of BNT162b2. The levels of IgG, IgM, and IgA against RBD were measured by enzyme-linked immunosorbent assay before and after the first and second vaccination, respectively. The relationship between antibody levels and several factors including age, gender, and hypertension were analyzed. Virus-neutralizing activity in sera was measured to determine the correlation with the levels of antibodies. A chemiluminescent enzyme immunoassay (CLEIA) method to measure IgG against RBD was developed and validated for the clinical setting. RESULTS: The levels of all antibody isotypes were increased after vaccination. Among them, RBD-IgG was dramatically increased after the second vaccination. The IgG levels in females were significantly higher than in males. There was a negative correlation between age and IgG levels in males. The IgG levels significantly correlated with the neutralizing activity. The CLEIA assay measuring IgG against RBD showed a reliable performance and a high correlation with neutralizing activity. CONCLUSIONS: Monitoring of IgG against RBD is a powerful tool to predict the efficacy of SARS-CoV-2 vaccination and provides useful information in considering a personalized vaccination strategy for COVID-19.

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Detailed Multiplex Analysis of SARS-CoV-2 Specific Antibodies in COVID-19 Disease

Frontiers in Immunology ◽

10.3389/fimmu.2021.695230 ◽

2021 ◽

Vol 12 ◽

Author(s):

Siggeir F. Brynjolfsson ◽

Hildur Sigurgrimsdottir ◽

Elin D. Einarsdottir ◽

Gudrun A. Bjornsdottir ◽

Brynja Armannsdottir ◽

...

Keyword(s):

Antibody Response ◽

Immunological Response ◽

Receptor Binding Domain ◽

Igg Antibody ◽

Nucleocapsid Proteins ◽

The Third ◽

Antibody Isotypes ◽

Iga Antibodies ◽

Set Up ◽

Antibody Levels

A detailed understanding of the antibody response against SARS-CoV-2 is of high importance, especially with the emergence of novel vaccines. A multiplex-based assay, analyzing IgG, IgM, and IgA antibodies against the receptor binding domain (RBD), spike 1 (S1), and nucleocapsid proteins of the SARS-CoV-2 virus was set up. The multiplex-based analysis was calibrated against the Elecsys® Anti-SARS-CoV-2 assay on a Roche Cobas® instrument, using positive and negative samples. The calibration of the multiplex based assay yielded a sensitivity of 100% and a specificity of 97.7%. SARS-CoV-2 specific antibody levels were analyzed by multiplex in 251 samples from 221 patients. A significant increase in all antibody types (IgM, IgG, and IgA) against RBD was observed between the first and the third weeks of disease. Additionally, the S1 IgG antibody response increased significantly between weeks 1, 2, and 3 of disease. Class switching appeared to occur earlier for IgA than for IgG. Patients requiring hospital admission and intensive care had higher levels of SARS-CoV-2 specific IgA levels than outpatients. These findings describe the initial antibody response during the first weeks of disease and demonstrate the importance of analyzing different antibody isotypes against multiple antigens and include IgA when examining the immunological response to COVID-19.

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ANTIBODY RESPONSE OF HUMAN BEINGS FOLLOWING VACCINATION WITH INFLUENZA VIRUSES

Journal of Experimental Medicine ◽

10.1084/jem.75.5.495 ◽

1942 ◽

Vol 75 (5) ◽

pp. 495-511 ◽

Cited By ~ 28

Author(s):

G. K. Hirst ◽

E. R. Rickard ◽

Loring Whitman ◽

F. L. Horsfall

Keyword(s):

Influenza Virus ◽

Antibody Response ◽

Influenza A ◽

Geometric Mean ◽

Allantoic Fluid ◽

Influenza Viruses ◽

Human Beings ◽

Significant Difference ◽

Antibody Levels

Eleven different preparations of influenza virus were used to vaccinate large groups of human beings. The antibody response to these vaccines was measured by means of the in vitro agglutination inhibition test, and the geometric mean titers of sera taken 2 weeks after vaccination were compared. From these comparisons the following conclusions were drawn: 1. There was a wide individual variation in the antibody response of human beings to the same preparation of influenza virus administrated subcutaneously. The amount of antibody produced by a group with a low prevaccination antibody level was very nearly the same as the amount produced by groups that had higher initial levels. 2. The use of the X strain of distemper virus in the preparation of an influenza vaccine did not enhance the antigenicity of the influenza virus present. 3. Within certain limits the mean antibody response of human beings increased as the amount of virus injected was increased. When large amounts of influenza A virus were given, the antibody response was of the same order of magnitude as that which occurred following actual infection by this virus. 4. When the vaccine was prepared from allantoic fluid, there was no significant difference in the antibody response of human beings given active virus, formalin-inactivated virus, heat-inactivated virus, or virus inactivated by the drying process. 5. Ground infected chick embryos, when diluted with infected allantoic fluid, gave a greater antibody response than allantoic fluid alone (when the virus remained active). The antigenicity of such a preparation was diminished when the virus was inactivated by formalin. 6. Antibody levels 6 and 9 weeks after vaccination showed a marked drop from the 2-week postvaccination levels. In a small group the antibody levels at 5 months were still further reduced. Those individuals who possessed the higher titers tended to lose their antibodies faster than did those at a lower level.

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