scholarly journals Distinct SARS-CoV-2 antibody reactivity patterns elicited by natural infection and mRNA vaccination

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Rafael Assis ◽  
Aarti Jain ◽  
Rie Nakajima ◽  
Algis Jasinskas ◽  
Saahir Khan ◽  
...  

AbstractWe analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8476 finger stick blood specimens were collected before and after a vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing antigens from SARS-CoV-2, SARS, MERS, Common CoV, and Influenza. Twenty-six percent of specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive; out of 852 seropositive individuals 77 had symptoms and 9 sought medical care. The antibody response was predominantly against nucleocapsid (NP), full length, and S2 domain of spike. Anti-receptor binding domain (RBD) reactivity was low and not cross-reactive against SARS S1 or SARS RBD. A vaccination campaign at the University of California Irvine Medical Center (UCIMC) started on December, 2020 and 6724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% pre-vaccination to 79% post-vaccination in January, 93% in February, and 99% in March. mRNA vaccination induced higher antibody levels than natural exposure, especially against the RBD domain and cross-reactivity against SARS RBD and S1 was observed. Nucleocapsid protein antibodies can be used to distinguish vaccinees to classify pre-exposure to SARS-CoV-2 Previously infected individuals developed higher antibody titers to the vaccine than non pre-exposed individuals. Hospitalized patients in intensive care with severe disease reach significantly higher antibody levels than mild cases, but lower antibody levels compared to the vaccine. These results indicate that mRNA vaccination rapidly induces a much stronger and broader antibody response than SARS-CoV-2 infection.

2021 ◽  
Author(s):  
Rafael Ramiro de Assis ◽  
Aarti Jain ◽  
Rie Nakajima ◽  
Algis Jasinskas ◽  
Saahir Kahn ◽  
...  

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.


2021 ◽  
Author(s):  
Massimo La Raja ◽  
Monia Pacenti ◽  
Ileana Grimaldi ◽  
Caterina Boldrin ◽  
Margherita Cattai ◽  
...  

From April 2020 through May 2021 in Padova Province 3395 COVID-19 recovered patients were recruited as potential convalescent plasma donors and tested for SARS-CoV-2 antibodies. Since January 2021 COVID-19 vaccination campaign began in Italy, the impact of vaccination on antibody levels and suspect vaccine breakthrough infections in these subjects were investigated. Post-vaccination anti-Sars-Cov-2 antibody level in 54 previously infected subjects had an exponential increase compared to pre-vaccination level regardless of the number of vaccine doses. However after 100 days from vaccination SARS-CoV-2 antibody level tends to decline. Post-vaccination primary infections were detected in 15 cases, with 3 possible breakthrough infections after a full vaccination course. In these cases, antibody response after infection was present but weaker than the one of subjects vaccinated after natural infection. A trend toward stronger antibody response was observed with increasing distance between natural infection and vaccination. Additionally, 2 cases of asymptomatic reinfections are also discussed.


2021 ◽  
Author(s):  
Rafael Assis ◽  
Aarti Jain ◽  
Rie Nakajima ◽  
Al Jasinskas ◽  
Saahir Kahn ◽  
...  

AbstractWe analyzed data from two ongoing serologic surveys, a longitudinal cohort of health care workers (HCW) from the University of California Irvine Medical Center (Orange County, CA, USA), collected from May and December 2020 through March 2021, and a cross sectional county-wide study in July 2020 (actOC; Orange County, CA) and a more focused community study in the city of Santa Ana (Santa Ana Cares; Orange County, CA, USA), collected in December 2020 - in order to compare the antibody responses to SARS-CoV-2 natural infection and vaccination. In addition, we serially tested 9 volunteers at multiple time points to analyze the time course of vaccine-induced antibody response in more detail. In May 2020, 1060 HCW were enrolled and had finger stick samples collected. Finger stick samples were again collected in December 2020, before vaccination, as well as January, February and March 2021 during vaccination campaign. A total of 8,729 finger stick blood specimens were probed and analyzed for IgG and IgM antibodies using a coronavirus antigen microarray (COVAM).The microarray contained 10 SARS-CoV-2 antigens including nucleocapid protein (NP) and several varying fragments of the spike protein, as well as 4 SARS, 3 MERS, 12 Common CoV, and 8 Influenza antigens.Based on a random forest based prediction algorithm, between May and December, prior to vaccine rollout, we observed that seropositivity in the HCW cohort increased from 4.5% to 13%. An intensive vaccination campaign with mRNA vaccines was initiated on December 16, 2020 and 6,724 healthcare workers were vaccinated within 3 weeks. The observed seropositivity of the HCW specimens taken in the last week of January 2021 jumped to 78%, and by the last week in February it reached 93%, and peaked at 98% seropositive in March. The antibody profile induced by natural exposure differed from the profile induced after mRNA vaccination. Messenger RNA vaccines induced elevated antibody (Ab) reactivity levels against the Receptor Binding Domain (RBD) domain of SARS-CoV-2 spike, and cross-reactive responses against SARS and MERS RBD domains. Nucleocapsid protein (NP), which is an immunodominant antigen induced after natural exposure, is not present in the vaccine and can be used as a biomarker of past exposure. The results show that naturally-exposed individuals mount a stronger anti-spike response upon vaccination than individuals that were not previously exposed. Longitudinal specimens taken at approximately weekly intervals from 9 individuals show variation in the response to the mRNA vaccine, with some showing a vigorous response to the first dose (prime) and others requiring a subsequent dose (boost) to reach high anti-SARS-CoV-2 levels. Antibody titers determined by serial dilution of the specimens were used to accurately compare antibody levels in these samples. mRNA vaccinees after the boost have higher Ab titers (up to 10 times higher) than convalescent plasmas from donors who recovered from natural infection. The results of this study exemplify the time course and outcomes expected from similar mRNA mass vaccination campaigns conducted in other institutions.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ioannis P. Trougakos ◽  
Evangelos Terpos ◽  
Christina Zirou ◽  
Aimilia D. Sklirou ◽  
Filia Apostolakou ◽  
...  

Abstract Background Coronavirus SARS-CoV-2, the causative agent of COVID-19, has caused a still evolving global pandemic. Given the worldwide vaccination campaign, the understanding of the vaccine-induced versus COVID-19-induced immunity will contribute to adjusting vaccine dosing strategies and speeding-up vaccination efforts. Methods Anti-spike-RBD IgGs and neutralizing antibodies (NAbs) titers were measured in BNT162b2 mRNA vaccinated participants (n = 250); we also investigated humoral and cellular immune responses in vaccinated individuals (n = 21) of this cohort 5 months post-vaccination and assayed NAbs levels in COVID-19 hospitalized patients (n = 60) with moderate or severe disease, as well as in COVID-19 recovered patients (n = 34). Results We found that one (boosting) dose of the BNT162b2 vaccine triggers robust immune (i.e., anti-spike-RBD IgGs and NAbs) responses in COVID-19 convalescent healthy recipients, while naïve recipients require both priming and boosting shots to acquire high antibody titers. Severe COVID-19 triggers an earlier and more intense (versus moderate disease) immune response in hospitalized patients; in all cases, however, antibody titers remain at high levels in COVID-19 recovered patients. Although virus infection promotes an earlier and more intense, versus priming vaccination, immune response, boosting vaccination induces antibody titers significantly higher and likely more durable versus COVID-19. In support, high anti-spike-RBD IgGs/NAbs titers along with spike (vaccine encoded antigen) specific T cell clones were found in the serum and peripheral blood mononuclear cells, respectively, of vaccinated individuals 5 months post-vaccination. Conclusions These findings support vaccination efficacy, also suggesting that vaccination likely offers more protection than natural infection. Graphical abstract


2021 ◽  
Vol 10 (18) ◽  
pp. 4204
Author(s):  
Marcello Salvaggio ◽  
Federica Fusina ◽  
Filippo Albani ◽  
Maurizio Salvaggio ◽  
Rasula Beschi ◽  
...  

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.


1980 ◽  
Vol 89 (3_suppl) ◽  
pp. 351-356 ◽  
Author(s):  
John L. Sloyer ◽  
Laurel J. Karr ◽  
John H. Ploussard ◽  
Gerald D. Schiffman

The serum antibody response to purified pneumococcal capsular polysaccharides (PCP) was determined in four groups of infants ranging in age from 3 to 24 months. Group 1 consisted of eight infants immunized with an octavalent vaccine containing serotypes 1, 3, 6, 7, 14, 18, 19 and 23 (PCP-8). Group 1 received 25 μg of each serotype at 3–6 months of age and again at 18–24 months. The antibody response after the second immunization was compared to a group of nine patients receiving a primary immunization at 18–24 months and to a group of ten age-matched controls receiving saline placebo. There were no significant differences in mean serum antibody levels between the two groups receiving the PCP-8. A fourth group of 44 infants between 6 and 21 months of age received either PCP-7 or PCP-8 and were followed for two years, at which time simultaneous injections of both vaccines were administered. Types 2, 3, 7, and 8 were most immunogenic but levels six months after immunization were approximately the same as for unimmunized controls with the exception of serotypes 3 and 7 which persisted for about two years. The class of antibody induced either by natural infection or by immunization was preferentially IgG and it was more often induced by the former. There were no significant differences between the serotypes of pneumococci isolated from nasopharyngeal cultures regardless of which vaccine was administered. Finally, the least immunogenic serotypes include 4, 6, 14, 19, and 23 and these are the only serotypes thus far associated with otitis media after immunization. The results suggest that PCP do not induce a lasting immune tolerance at the dose administered in this study; PCP are not very immunogenic in the young infant; PCP antibody tends to rise naturally; IgG antibody is preferentially induced; nasopharyngeal colonization is not altered by PCP immunization; and an association may exist between PCP immunogenicity and subsequent onset of otitis media.


2015 ◽  
Vol 43 (2) ◽  
pp. 273-281 ◽  
Author(s):  
Gregory J. Challener ◽  
Jonathan D. Jones ◽  
Adam J. Pelzek ◽  
B. JoNell Hamilton ◽  
Gilles Boire ◽  
...  

Objective.The presence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) indicates a breach in immune tolerance. Recent studies indicate that this breach extends to homocitrullination of lysines with the formation of anti-carbamylated protein (anti-CarP) antibodies. We analyzed the clinical and serologic relationships of anti-CarP in 2 RA cohorts.Methods.Circulating levels of immunoglobulin G anti-CarP antibodies were determined by ELISA in established (Dartmouth-Hitchcock Medical Center) and early (Sherbrooke University Hospital Center) cohorts and evaluated for anticyclic citrullinated peptide antibodies (anti-CCP), specific ACPA, and rheumatoid factor (RF) levels using the Student t test and correlation analysis.Results.We identified elevated anti-CarP antibodies titers in 47.0% of seropositive patients (Dartmouth, n = 164), with relationships to anti-CCP (p < 0.0001) and IgM-RF (p = 0.001). Similarly, 38.2% of seropositive patients from the Sherbrooke cohort (n = 171) had elevated anti-CarP antibodies; titers correlated to anti-CCP (p = 0.01) but not IgM-RF (p = 0.09). A strong correlation with anti-Sa was observed: 47.9% anti-Sa+ patients were anti-CarP antibodies+ versus only 25.4% anti-Sa− in the Sherbrooke cohort (p = 0.0002), and 62.6% anti-Sa+ patients versus 26.9% anti-Sa− were anti-CarP antibodies+ in Dartmouth (p < 0.0001). We found a more variable response for reactivity to citrullinated fibrinogen or to citrullinated peptides from fibrinogen and α enolase.Conclusion.In 2 North American RA cohorts, we observed a high prevalence of anti-CarP antibody positivity. We also describe a surprising and unexpected association of anti-CarP with anti-Sa antibodies that could not be explained by cross-reactivity. Further, considerable heterogeneity exists between anti-CarP reactivity and other citrullinated peptide reactivity, raising the question of how the pathogenesis of antibody responses for carbamylated proteins and citrullinated proteins may be linked in vivo.


2006 ◽  
Vol 134 (6) ◽  
pp. 1303-1312 ◽  
Author(s):  
A. J. VYSE ◽  
N. J. GAY ◽  
L. M. HESKETH ◽  
R. PEBODY ◽  
P. MORGAN-CAPNER ◽  
...  

A mixture modelling technique is applied to age-specific frequency distributions of quantitative results from serological surveys for measles, mumps and rubella using samples collected across the age range in England and Wales in 2000. In accordance with previous studies the analysis suggests that the antibody response to natural infection is stronger than that produced by vaccination, that vaccine-induced antibody levels wane with time and that levels of vaccine-induced antibody response vary for each virus infection being strongest for rubella and weakest for mumps. The current mumps epidemic in the United Kingdom is focused in cohorts born during 1982–1987 who were too old to have received routine MMR vaccination. In the cohort born in 1981–1985 the model estimates that 7·5% have no evidence of mumps specific IgG and 24·9% have the lowest level of detectable antibody. The similar proportions of mumps antibody in these categories among cohorts with opportunity for 1 or 2 doses of vaccine is a concern, as the degree to which these individuals are protected is unclear. Investigations into the efficacy of two doses of a mumps containing vaccine should be a priority during the current epidemic.


2021 ◽  
Author(s):  
Enrico Lavezzo ◽  
Monia Pacenti ◽  
Laura Manuto ◽  
Caterina Boldrin ◽  
Margherita Cattai ◽  
...  

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.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S384-S385
Author(s):  
Bhagyashri D Navalkele ◽  
Jose Lucar ◽  
James B Brock ◽  
Jason Parham

Abstract Background Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus affected healthcare workers (HCWs) adding additional burden on staffing shortages. COVID-19 vaccination (mRNA 1273 and BNT162b2) has been shown to protect against severe disease, death and reduced risk of asymptomatic infection and transmission from fully vaccinated individuals. Here, we present the impact of COVID-19 vaccination (CoVac) on risk of developing COVID-19 based on test results among unvaccinated and vaccinated HCWs. Methods Our academic medical center with 11,785 HCWs on its Jackson campus initiated non-mandatory CoVac among HCWs with BNT162b2 on December 16, 2020. Individuals ≥ 2 weeks after 1st dose of vaccine were defined as partially vaccinated and those ≥2 weeks from 2nd dose of vaccine were defined as fully vaccinated. Per facility policy, all symptomatic HCWs (irrespective of vaccination status) were recommended to undergo SARS-CoV-2 RT-PCR testing. Asymptomatic HCWs were also tested upon household exposure, however, this policy was changed on March 9th 2021 to allow fully vaccinated asymptomatic HCWs to work without need for quarantine or testing. Universal masking policy among HCWs remained effective at our center during study period. Results Between the launch of COVID-19 vaccination on December 16, 2020 and April 30, 2021, 5,855 HCWs received one dose of vaccine, and 5,687 received both doses. A total of 1,329 unique HCWs underwent COVID-19 testing between January 4, 2021 and April 30, 2021. Of those, 217 (16.3%) tested positive for SARS-CoV-2 infection; 204 were unvaccinated, 7 were partially vaccinated, and 6 were fully vaccinated (figure 1). Of the 6 fully vaccinated employees, 1 was asymptomatic (testing for travel purposes), 4 had mild symptoms, and one elderly employee required hospitalization with oxygen supplementation and had a complete recovery. No facility outbreaks were reported related to asymptomatic, work exposed, fully vaccinated HCWs. Unvaccinated healthcare workers were more likely to test positive for SARS-CoV-2 compared to partially and fully vaccinated healthcare workers. Conclusion COVID-19 vaccination protected HCWs by reducing risk for developing COVID-19. Vaccinating healthcare workers is a crucial infection prevention measure to reduce disease burden, avoid staffing shortages and create a safe environment in the healthcare facility to prevent transmission to other staff and at-risk patients. Disclosures All Authors: No reported disclosures


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