scholarly journals SARS-CoV-2 induces a durable and antigen specific humoral immunity after asymptomatic to mild COVID-19 infection

2021 ◽  
Author(s):  
Sebastian Havervall ◽  
August Jernbom Falk ◽  
Jonas Klingström ◽  
Henry Ng ◽  
Nina Greilert-Norin ◽  
...  
Keyword(s):  
Post Infection ◽  
Nucleocapsid Protein ◽  
Healthcare Workers ◽  
Humoral Response ◽  
Population Based ◽  
Target Antigen ◽  
Neutralization Capacity ◽  
Study Participants ◽  
Antibody Levels ◽  
Antibody Kinetics

AbstractCurrent SARS-CoV-2 serological assays generate discrepant results, and the longitudinal characteristics of antibodies targeting various antigens after asymptomatic to mild COVID-19 are yet to be established. This longitudinal cohort study including 1972 healthcare workers, of which 386 participants exhibited antibodies against the SARS-CoV-2 spike antigen at study inclusion, reveal that these antibodies remain detectable in the vast majority of participants, 98%, at least four months post infection, despite having had no or mild symptoms. These antibody levels did not differ from those found in 59 convalescent COVID-19 patients (p=0.7). Virus neutralization capacity was confirmed by microneutralization assay in 93% of study participants at least four months post infection. Contrary to antibodies targeting the spike protein, antibodies against the nucleocapsid protein were only detected in 68% of previously anti-nucleocapsid IgG positive healthcare workers, and these four-month follow-up levels were substantially lower in healthcare workers than in convalescent COVID-19 patients (p=2*10-5). Our findings support a durable and functional humoral response after SARS-CoV-2 infection, even after no or mild symptoms. We further demonstrate differences in antibody kinetics depending on the antigen, arguing against the use of the nucleocapsid protein as target antigen in population-based SARS-CoV-2 serological surveys.

scholarly journals SARS-CoV-2 induces a durable and antigen specific humoral immunity after asymptomatic to mild COVID-19 infection

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262169
Author(s):  
Sebastian Havervall ◽  
August Jernbom Falk ◽  
Jonas Klingström ◽  
Henry Ng ◽  
Nina Greilert-Norin ◽  
...  
Keyword(s):  
Post Infection ◽  
Nucleocapsid Protein ◽  
Healthcare Workers ◽  
Humoral Response ◽  
Population Based ◽  
Target Antigen ◽  
Neutralization Capacity ◽  
Study Participants ◽  
Antibody Kinetics ◽  
Study Inclusion

Current SARS-CoV-2 serological assays generate discrepant results, and the longitudinal characteristics of antibodies targeting various antigens after asymptomatic to mild COVID-19 are yet to be established. This longitudinal cohort study including 1965 healthcare workers, of which 381 participants exhibited antibodies against the SARS-CoV-2 spike antigen at study inclusion, reveal that these antibodies remain detectable in most participants, 96%, at least four months post infection, despite having had no or mild symptoms. Virus neutralization capacity was confirmed by microneutralization assay in 91% of study participants at least four months post infection. Contrary to antibodies targeting the spike protein, antibodies against the nucleocapsid protein were only detected in 80% of previously anti-nucleocapsid IgG positive healthcare workers. Both anti-spike and anti-nucleocapsid IgG levels were significantly higher in previously hospitalized COVID-19 patients four months post infection than in healthcare workers four months post infection (p = 2*10−23 and 2*10−13 respectively). Although the magnitude of humoral response was associated with disease severity, our findings support a durable and functional humoral response after SARS-CoV-2 infection even after no or mild symptoms. We further demonstrate differences in antibody kinetics depending on the antigen, arguing against the use of the nucleocapsid protein as target antigen in population-based SARS-CoV-2 serological surveys.

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

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.

scholarly journals Humoral response to the BBIBP-CorV vaccine over time in healthcare workers with or without exposure to SARS-CoV-2

2021 ◽  
Author(s):  
María Noel Badano ◽  
Florencia Sabbione ◽  
Irene Keitelman ◽  
Matias Pereson ◽  
Natalia Aloisi ◽  
...  
Keyword(s):  
Single Dose ◽  
Sharp Increase ◽  
Healthcare Workers ◽  
Humoral Response ◽  
Igg Antibody ◽  
Antibody Titers ◽  
Humoral Responses ◽  
Antibody Levels ◽  
Over Time

AbstractSARS-CoV-2-specific humoral response was analyzed over time in a group of healthcare workers with or without exposure to SARS-CoV-2, who underwent vaccination with BBIBP-CorV (Sinopharm) vaccine in Argentina.Seroconversion rates in unexposed subjects after the first and second doses were 40% and 100%, respectively, showing a significant increase in antibody concentrations from dose 1 to dose 2 (p<0.0001).The highest antibody concentrations were found in younger subjects and women, remaining significantly associated in a multivariable linear regression model (p=0.005).A single dose of the BBIBP-CorV vaccine induced a strong antibody response in individuals with prior SARS-CoV-2infection, while a second dose did not increase this response. A sharp increase in antibody concentrations was observed following SARS-CoV-2 infection in those participants who became infected after the first and second doses (p=0.008).Individuals with SARS-CoV-2 exposure prior to vaccination showed significantly higher anti-spike IgG antibody levels, at all-time points, than those not exposed (p<0.001). Higher antibody titers were induced by a single dose in previously SARS-CoV-2 infected individuals than those induced in naïve subjects by two doses of the vaccine (p<0.0001). Three months after the second dose both groups showed a decline in antibody levels, being more abrupt in unexposed subjects.Overall, our results showed a trend towards lower antibody concentrations over time following BBIBP-CorV vaccination. Sex and age seem to influence the magnitude of the humoral response in unexposed subjects while the combination of exposure to SARS-CoV-2 plus vaccination, whatever the sequence of the events was, produced a sharp increase in antibody levels.Evaluation of the humoral responses over time and the analysis of the induction and persistence of memory B and T cell responses, are needed to assess long-term immune protection induced by BBIBP-CorV vaccine.

scholarly journals Robust Neutralizing Antibody Levels Detected after Either SARS-CoV-2 Vaccination or One Year after Infection

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2003
Author(s):  
Stefan Glöckner ◽  
Franziska Hornung ◽  
Michael Baier ◽  
Sebastian Weis ◽  
Mathias W. Pletz ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Neutralization Titer ◽  
Neutralization Capacity ◽  
A Cell ◽  
One Year ◽  
Study Participants ◽  
Antibody Levels

Humoral immunity after infection or after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been attributed a key part in mitigating the further transmission of the virus. In this study, we used a commercial anti-Spike immunoglobulin G (S-IgG) assay and developed a cell culture-based neutralization assay to understand the longitudinal course of neutralizing antibodies in both SARS-CoV2 infected or vaccinated individuals. We show that even more than one year after infection, about 78% of observed study participants remained seropositive concerning S-IgG antibodies. In addition, the serum of the individuals had stable neutralization capacity in a neutralization assay against a SARS-CoV-2 patient isolate from March 2020. We also examined volunteers after either homologous BNT162b2 prime-boost vaccination or heterologous AZD1222 prime/mRNA-based booster vaccination. Both the heterologous and the homologous vaccination regimens induced higher levels of neutralizing antibodies in healthy subjects when compared to subjects after a mild infection, showing the high effectiveness of available vaccines. In addition, we could demonstrate the reliability of S-IgG levels in predicting neutralization capacity, with 94.8% of seropositive samples showing a neutralization titer of ≥10, making it a viable yet cheap and easy-to-determine surrogate parameter for neutralization capacity.

scholarly journals Waning of SARS-CoV-2 Antibody levels response to inactivated cellular vaccine over 6 months among healthcare workers

2022 ◽  
Author(s):  
Monica Taminato ◽  
Ana Paula Cunha Chaves ◽  
Richarlisson Borges de Morais ◽  
Luiz Vinícius Leão Moreira ◽  
Danielle Dias Conte ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Serological Test ◽  
Demographic Data ◽  
Humoral Response ◽  
Igg Antibody ◽  
Serological Tests ◽  
Post Vaccination ◽  
Age Cohorts ◽  
Vaccine Booster ◽  
Antibody Levels

Background Health Care workers (HCW) are an important group affected by this pandemic and COVID-19 has presented substantial challenges for health professionals and health systems in many countries. The Brazilian vaccination plan implemented in October, so that third dose for HCW. However, the persistence of CoronaVac vaccine-induced immunity is unknown, and immunogenicity according to age cohorts may differ among individuals. Objective Evaluate the post vaccination immune humoral response and the relationship between post-vaccination seropositivity rates and demographic data among Healthcare Workers over 6 months after CoronaVac immunization. Methods A cross section study including Healthcare professionals vaccinated with CoronaVac for 6 months or more. The study was carried with the analysis of post-vaccination serological test to assess the levels of humoral response after vaccination. Results 329 participants were included. Among them, 76% were female. Overall, 18.5% were positive quantitative titles (IQR 42.87-125.5) and the negative group was 80%, quantitative titles (IQR 5.50-13.92). Conclusion It was possible to identify a group with positive quantitative titles in serological test for IgG antibody against the SARS-CoV-2. Further investigation is required to determine the durability of post-vaccination antibodies and how serological tests can be determine the ideal timing of vaccine booster doses.

scholarly journals Serological surveillance of SARS-CoV-2: trends and humoral response in a cohort of public health workers

2020 ◽  
Author(s):  
Ross J Harris ◽  
Heather J Whitaker ◽  
Nick J Andrews ◽  
Felicity Aiano ◽  
Zahin Amin-Chowdhury ◽  
...  
Keyword(s):  
Half Life ◽  
Healthcare Workers ◽  
Health Workers ◽  
Natural Infection ◽  
Humoral Response ◽  
Spike Protein ◽  
Positive Test ◽  
Public Health Workers ◽  
Serological Surveillance ◽  
Antibody Levels

AbstractBackgroundThere is considerable debate about the rate of antibody waning after SARS-CoV-2 infection, raising questions around long-term immunity following both natural infection and vaccination. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.MethodsThe serosurveillance cohort included office and laboratory-based staff and healthcare workers in 4 sites in England, who were tested monthly for SARS-CoV-2 spike protein and nucleoprotein IgG between 23rd March and 20th August 2020. Antibody levels from 21 days after a positive test were modelled using mixed effects regression models.FindingsIn total, 2247 individuals were recruited and 2014 (90%) had 3-5 monthly antibody tests. Overall, 272 (12.1%) of individuals had at least one positive/equivocal spike protein IgG result, with the highest proportion in a hospital site (22%), 14% in London and 2.1% in a rural area. Results were similar for nucleoprotein IgG. Following a positive result, 39/587 (6.6%) tested negative for nucleoprotein IgG and 52/515 (10.1%) for spike protein IgG. Nucleoprotein IgG declined by 6.4% per week (95% CI, 5.5-7.4%; half-life, 75 [95% CI, 66-89] days) and spike protein IgG by 5.8% (95% CI, 5.1-6.6%; half-life, 83 [95% CI, 73-96] days).ConclusionsOver the study period SARS-CoV-2 seropositivity was 8-10% overall and up to 21% in clinical healthcare workers. In seropositive individuals, nucleoprotein and spike protein IgG antibodies declined with time after infection and 50% are predicted to fall below the positive test threshold after 6 months.FundingPHE

scholarly journals Persistence of SARS-CoV-2 antibodies and symptoms in an Irish Healthcare Worker (HCW) setting: Results of the COVID Antibody Staff Testing (CAST) Study

2021 ◽  
Author(s):  
Joanna Griffin ◽  
Elizabeth Tully ◽  
Fiona Cody ◽  
Katherine Edwards ◽  
Kara Moran ◽  
...  
Keyword(s):  
Post Infection ◽  
Healthcare Workers ◽  
Clinical Symptoms ◽  
Maternity Hospital ◽  
Viral Rna ◽  
Serological Response ◽  
Rt Pcr ◽  
Protein Antigens ◽  
Gene Target ◽  
Study Participants

AbstractObjectivesThis study examined the natural history, including incidence and prevalence, of SARS-CoV-2 antibodies serially up to 6 months post infection in Irish Healthcare Workers (HCWs) at an academic tertiary maternity hospital, during the first pandemic peak from March to September 2020.DesignThis single centre observational study profiled SARS-CoV-2 incidence and infection using viral RNA detected using oro/nasopharyngeal swabs accompanied by serological assessment of study participants for the presence of S SARS-CoV-2 antibodies. Participant demographics were also collected alongside information on clinical symptoms and time to recovery. Real time polymerase-chain-reaction (RT-PCR) for viral RNA SARS-CoV-2 detection was performed using the Allplex™ SARS-CoV-2 three gene target 2019-nCoV assay (SeeGene Inc., Rep. of Korea) or the Xpert Xpress SARS-CoV-2 assay on the GeneXpert platform (Cepheid, USA). Blood samples were obtained at the time of initial swab and at up to 4 time points thereafter, for the serological assessment of antibodies against both the spike and nucleocapsid protein antigens of SARS-CoV-2. Serological response was measured using the Captia™ Anti-SARS-CoV-2 (IgG) ELISA (Trinity Biotech) as part of a clinical performance evaluation. Two other testing methods were also used; the Anti-SARS-CoV-2 ELISA (IgG) assay (EuroImmun) and the Abbott Anti-SARS-CoV-2 IgG 75 kit on the Architect™ i2000SR instrument (Abbott Laboratories).SettingAcademic Tertiary Maternity Hospital in Dublin, Ireland.ParticipantsWe invited symptomatic and asymptomatic healthcare workers employed at the Rotunda Maternity Hospital to participate in the CAST study.Main Outcome MeasuresThe CAST study aimed to examine incidence and clinical symptoms of SARS-CoV-2 in HCWs and to determine the presence and longevity of antibodies in this group. We also sought to examine the clinical utility of the Captia™ Anti-SARS-CoV-2 (IgG) ELISA (Trinity Biotech) and to compare it to the current “accepted” gold standard platform in Ireland.ResultsBy July 2020, 398 molecular tests had been completed on symptomatic staff with clinical suspicion of SARS-CoV-2 infection. In this cohort, 14% (n=54/398) had SARS-CoV-2 RNA detected by RT-PCR. The CAST study enrolled 137 HCWs with 86 participants symptomatic at time of swab collection and a further 51 asymptomatic control participants. SARS-CoV-2 RNA was detected in 52% (n=45/86) symptomatic study participants and serological positivity was confirmed in 98% (n=44/45) of those participants. Asymptomatic SARS-CoV-2 RNA infection was detected in 4% (n=2/51) of control participants with a seropositivity rate in this group of 8% (n=4/51). We demonstrated that 95% of SARS-CoV-2 PCR positive participants have detectable levels of antibodies at 100 days post infection, which persisted in 91% of participants at day 160+. Ongoing symptoms up to six months post infection were present in 50% of study participants with positive PCR and serology results. These data will be important to consider for long-term workforce planning in a healthcare setting, as the ongoing pandemic continues.FundingThe CAST study was supported by the Rotunda Hospital and Trinity Biotech.

scholarly journals Assessment of S1, S2 and NCP-specific IgM, IgA, and IgG antibody kinetics in acute SARS-CoV-2 infection by a microarray and twelve other immunoassays

2021 ◽  
Author(s):  
Georg Semmler ◽  
Marianna Theresia Traugott ◽  
Marianne Graninger ◽  
Wolfgang Hoepler ◽  
Tamara Seitz ◽  
...  
Keyword(s):  
Rapid Test ◽  
Tracheal Aspirate ◽  
Target Antigen ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
Detection Rates ◽  
Specific Igg ◽  
Antibody Levels ◽  
Antibody Kinetics ◽  
Specific Igg Antibodies

In this study, we comprehensively analyzed multispecific antibody kinetics of different immunoglobulins in hospitalized patients with acute SARS-CoV-2 infection. Three-hundred-fifty-four blood samples longitudinally obtained from 81 IgG seroconverting CoVID-19 patients were quantified for spike (S)1, S2, and nucleocapsid protein (NCP)- specific IgM, IgA, IgG, and total Ig antibodies using a microarray, eleven different ELISAs/CLIAs, and one rapid test by seven manufacturers. The assays’ specificity was assessed in 130 non-CoVID19 pneumonia patients. Using the microarray, NCP-specific IgA and IgG antibodies continuously displayed higher detection rates during acute CoVID-19 than S1- and S2-specific ones. S1-specific IgG antibodies, however, reached higher peak values. Until the 26th-day post symptom onset, all patients developed IgG responses against S1, S2, and NCP, respectively. Although detection rates by ELISAs/CLIAs generally resembled those of the microarray, corresponding to the target antigen, sensitivities and specificities varied among all tests. Notably, patients with more severe CoVID-19 displayed higher IgG and IgA levels, but this difference was mainly observed with S1-specific immunoassays. In patients with high SARS-CoV-2 levels in the lower respiratory tract, we observed high detection rates of IgG and total Ig immunoassays with a particular rise of S1-specific IgG antibodies when viral concentrations in the tracheal aspirate subsequently declined over time. In summary, our study demonstrates that differences in sensitivity among commercial immunoassays during acute SARS-CoV-2 infection are only partly related to the target antigen. Importantly, our data indicate that NCP-specific IgA and IgG antibodies are detected earlier, while higher S1-specific IgA antibody levels occur in severely ill patients.

scholarly journals Determinants of early antibody responses to COVID-19 mRNA vaccines in exposed and naive healthcare workers

2021 ◽  
Author(s):  
Gemma Moncunill ◽  
Ruth Aguilar ◽  
Marta Ribes ◽  
Natalia Ortega ◽  
Rocío Rubio ◽  
...  
Keyword(s):  
Health Care Workers ◽  
Healthcare Workers ◽  
Healthy Individuals ◽  
Wild Type ◽  
Post Vaccination ◽  
Neutralization Capacity ◽  
Care Workers ◽  
Neutralizing Capacity ◽  
One Year ◽  
Antibody Levels

Background Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naive adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. Methods We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. Findings Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects. A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with lower neutralization and antibody levels. Among fully vaccinated, 6.3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. Interpretation Our data support administering a single-dose in pre-exposed healthy individuals. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year.

scholarly journals Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

2021 ◽  
Vol 7 (22) ◽  
pp. eabg7156
Author(s):  
So-Hee Hong ◽  
Hanseul Oh ◽  
Yong Wook Park ◽  
Hye Won Kwak ◽  
Eun Young Oh ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
Statistical Significance ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
Antibody Levels ◽  
Further Development

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

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