scholarly journals Persistence of Neutralizing Antibodies to SARS-CoV-2 in First Wave Infected Individuals at Ten Months Post-Infection: The UnIRSA Cohort Study

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2270
Author(s):  
Gloria Griffante ◽  
Shikha Chandel ◽  
Daniela Ferrante ◽  
Valeria Caneparo ◽  
Daniela Capello ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Natural Infection ◽  
Large Fraction ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Northern Italy ◽  
Serum Samples ◽  
Neutralization Titer ◽  
Igg Antibody

Longitudinal mapping of antibody-based SARS-CoV-2 immunity is critical for public health control of the pandemic and vaccine development. We performed a longitudinal analysis of the antibody-based immune response in a cohort of 100 COVID-19 individuals who were infected during the first wave of infection in northern Italy. The SARS-CoV-2 humoral response was tested using the COVID-SeroIndex, Kantaro Quantitative SARS-CoV-2 IgG Antibody RUO Kit (R&D Systems, Bio-Techne, Minneapolis, USA) and pseudotype-based neutralizing antibody assay. Using sequential serum samples collected from 100 COVID-19 recovered individuals from northern Italy—mostly with mild disease—at 2 and 10 months after their first positive PCR test, we show that 93% of them seroconverted at 2 months, with a geometric mean (GeoMean) half-maximal neutralization titer (NT50) of 387.9. Among the 35 unvaccinated subjects retested at 10 months, 7 resulted seronegative, with an 80% drop in seropositivity, while 28 showed decreased anti-receptor binding domain (RBD) and anti-spike (S) IgG titers, with a GeoMean NT50 neutralization titer dropping to 163.5. As an NT50 > 100 is known to confer protection from SARS-CoV-2 re-infection, our data show that the neutralizing activity elicited by the natural infection has lasted for at least 10 months in a large fraction of subjects.

scholarly journals Antibody titers measured by commercial assays are correlated with neutralizing antibody titers calibrated by international standards

2021 ◽  
Author(s):  
Yu-An Kung ◽  
Chung-Guei Huang ◽  
Sheng-Yu Huang ◽  
Kuan-Ting Liu ◽  
Peng-Nien Huang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Diagnostic Techniques ◽  
International Standards ◽  
World Health ◽  
Serum Samples ◽  
Antibody Titers ◽  
Health Organization

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.

Prevalence and Persistence of Maternal Dengue Neutralizing Antibodies in Infants From Central and Southern Thailand: A Retrospective Cohort Study

2019 ◽  
Vol 31 (4) ◽  
pp. 288-295 ◽  
Author(s):  
Adrienne Guignard ◽  
François Haguinet ◽  
Stéphanie Wéry ◽  
Phirangkul Kerdpanich
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Maternal Antibodies ◽  
Childhood Immunization ◽  
Serum Samples ◽  
Denv Serotypes ◽  
Antibody Titers ◽  
Antibody Kinetics

Understanding maternal dengue virus (DENV) neutralizing antibody kinetics in infants remains timely to develop a safe and effective childhood immunization. This retrospective study evaluated the prevalence and persistence of maternal antibody titers against DENV serotypes 1 to 4 in 139 Thai infants at 2, 6, and 7 months of age, using serum samples collected in a vaccination trial ( http://clinicaltrials.gov ; NCT00197275). Neutralizing antibodies against all 4 DENV serotypes were detected in 87.8% and 22.9% of infants at 2 and 7 months, respectively. At 2 months, DENV-4 neutralizing antibody geometric mean titers were notably lower (80) compared with DENV-1 to DENV-3 (277-471). Our results corroborate previous findings that DENV-1 to DENV-4 maternal antibodies persist at 7 months despite titers decrease from 2 months onwards. As persisting maternal antibodies may inhibit immune responses in DENV-vaccinated infants, a comprehensive understanding of DENV antibody kinetics is required in the perspective of vaccine development for infants.

scholarly journals SARS-CoV-2 antibodies remain detectable 12 months after infection and antibody magnitude is associated with age and COVID-19 severity

2021 ◽  
Author(s):  
Eric D. Laing ◽  
Nusrat J. Epsi ◽  
Stephanie A. Richard ◽  
Emily C. Samuels ◽  
Wei Wang ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Serum Samples ◽  
Military Hospitals ◽  
Igg Binding ◽  
One Year

ABSTRACTImportanceThe persistence of SARS-CoV-2 antibodies may be a predictive correlate of protection for both natural infections and vaccinations. Identifying predictors of robust antibody responses is important to evaluate the risk of re-infection / vaccine failure and may be translatable to vaccine effectiveness.ObjectiveTo 1) determine the durability of anti-SARS-CoV-2 IgG and neutralizing antibodies in subjects who experienced mild and moderate to severe COVID-19, and 2) to evaluate the correlation of age and IgG responses to both endemic human seasonal coronaviruses (HCoVs) and SARS-CoV-2 according to infection outcome.DesignLongitudinal serum samples were collected from PCR-confirmed SARS-CoV-2 positive participants (U.S. active duty service members, dependents and military retirees, including a range of ages and demographics) who sought medical treatment at seven U.S. military hospitals from March 2020 to March 2021 and enrolled in a prospective observational cohort study.ResultsWe observed SARS-CoV-2 seropositivity in 100% of inpatients followed for six months (58/58) to one year (8/8), while we observed seroreversion in 5% (9/192) of outpatients six to ten months after symptom onset, and 18% (2/11) of outpatients followed for one year. Both outpatient and inpatient anti-SARS-CoV-2 binding-IgG responses had a half-life (T1/2) of >1000 days post-symptom onset. The magnitude of neutralizing antibodies (geometric mean titer, inpatients: 378 [246-580, 95% CI] versus outpatients: 83 [59-116, 95% CI]) and durability (inpatients: 65 [43-98, 95% CI] versus outpatients: 33 [26-40, 95% CI]) were associated with COVID-19 severity. Older age was a positive correlate with both higher IgG binding and neutralizing antibody levels when controlling for COVID-19 hospitalization status. We found no significant relationships between HCoV antibody responses and COVID-19 clinical outcomes, or the development of SARS-CoV-2 neutralizing antibodies.Conclusions and RelevanceThis study demonstrates that humoral responses to SARS-CoV-2 infection are robust on longer time-scales, including those arising from milder infections.However, the magnitude and durability of the antibody response after natural infection was lower and more variable in younger participants who did not require hospitalization for COVID-19. These findings support vaccination against SARS-CoV-2 in all suitable populations including those individuals that have recovered from natural infection.

scholarly journals A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity

2021 ◽  
Author(s):  
Vincent Legros ◽  
Solène Denolly ◽  
Manon Vogrig ◽  
Bertrand Boson ◽  
Eglantine Siret ◽  
...  
Keyword(s):  
Intensive Care ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Surface Protein ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Rapid Decline ◽  
Serum Samples ◽  
Immune Correlates ◽  
Human Coronaviruses

AbstractUnderstanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and, thus, for public health policy and vaccine development for COVID-19. In this study, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections, including patients with mild symptoms and also more severe forms, including those that required intensive care. We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers; conversely, patients with milder disease symptoms had heterogeneous nAb titers, and asymptomatic or exclusive outpatient-care patients had no or low nAbs. We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses. Moreover, we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2. Finally, we found that the D614G mutation in the spike protein, which has recently been identified as the current major variant in Europe, does not allow neutralization escape. Altogether, our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease, and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.

scholarly journals Two doses of the SARS-CoV-2 BNT162b2 vaccine enhances antibody responses to variants in individuals with prior SARS-CoV-2 infection

2021 ◽  
pp. eabj0847
Author(s):  
Richard A Urbanowicz ◽  
Theocharis Tsoleridis ◽  
Hannah J Jackson ◽  
Lola Cusin ◽  
Joshua D Duncan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Serum Samples ◽  
Igg Antibody ◽  
Enzyme Immunoassays ◽  
Antigenic Exposure ◽  
The Impact ◽  
Prior Infection

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of healthcare workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BTN162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351 and P.1 variants with increasing antigenic exposure, either through vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein-specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.

scholarly journals The receptor binding domain of SARS-CoV-2 spike is the key target of neutralizing antibody in human polyclonal sera

2020 ◽  
Author(s):  
Tara L. Steffen ◽  
E. Taylor Stone ◽  
Mariah Hassert ◽  
Elizabeth Geerling ◽  
Brian T. Grimberg ◽  
...  
Keyword(s):  
Antibody Response ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Antigenic Determinants ◽  
Receptor Binding Domain ◽  
Neutralization Capacity

AbstractNatural infection of SARS-CoV-2 in humans leads to the development of a strong neutralizing antibody response, however the immunodominant targets of the polyclonal neutralizing antibody response are still unknown. Here, we functionally define the role SARS-CoV-2 spike plays as a target of the human neutralizing antibody response. In this study, we identify the spike protein subunits that contain antigenic determinants and examine the neutralization capacity of polyclonal sera from a cohort of patients that tested qRT-PCR-positive for SARS-CoV-2. Using an ELISA format, we assessed binding of human sera to spike subunit 1 (S1), spike subunit 2 (S2) and the receptor binding domain (RBD) of spike. To functionally identify the key target of neutralizing antibody, we depleted sera of subunit-specific antibodies to determine the contribution of these individual subunits to the antigen-specific neutralizing antibody response. We show that epitopes within RBD are the target of a majority of the neutralizing antibodies in the human polyclonal antibody response. These data provide critical information for vaccine development and development of sensitive and specific serological testing.

scholarly journals One-Step Rapid Quantification of Serum Neutralizing Antibody after COVID-19 Vaccination by a High-Throughput Nanoplasmonic Sensor Platform

2021 ◽  
Author(s):  
Liping Huang ◽  
Ying Li ◽  
Luo Changyou ◽  
Nadia Touil ◽  
Hicham el Annaz ◽  
...  
Keyword(s):  
High Throughput ◽  
Vaccine Development ◽  
Limit Of Detection ◽  
Neutralizing Antibody ◽  
Serum Samples ◽  
Igg Antibody ◽  
Plasma Therapy ◽  
One Step ◽  
The One ◽  
Rapid Quantification

ABSTRACTThe COVID-19 vaccination efficacy depends on serum production level of the neutralizing IgG antibody (NA) specific to the receptor binding domain of SARS-Cov-2 spike protein. Therefore, a high-throughput rapid assay to measure the total SARS-CoV-2 NA level is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, vaccine development, and assessment. Here, we developed a nanoplasmonic immunosorbent assay (NanoPISA) platform for one-step rapid quantification of SARS-CoV-2 NAs in clinical serum samples for high-throughput evaluation of COVID-19 vaccine effectiveness. The NanoPISA platform enhanced by the use of nanoporous hollow gold nanoparticle coupling was able to detect SARS-CoV-2 NAs with a limit of detection of 0.1 ng/mL within 15 min. The one-step NanoPISA for SARS-CoV-2 NA detection in clinical specimens yielded good results, comparable to those obtained in the gold standard seroneutralization test and the surrogate virus neutralizing ELISA. Collectively, our findings indicate that the one-step NanoPISA may offer a rapid and high-throughput NA quantification platform for evaluating the effectiveness of COVID-19 vaccines.

scholarly journals A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma

2021 ◽  
pp. eabi8452
Author(s):  
Craig Fenwick ◽  
Priscilla Turelli ◽  
Céline Pellaton ◽  
Alex Farina ◽  
Jérémy Campos ◽  
...  
Keyword(s):  
High Throughput ◽  
Neutralizing Antibodies ◽  
Competitive Inhibition ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Serum Samples ◽  
Live Virus ◽  
Protein Variants

The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies in the serum of an individual indicates prior infection or vaccination. However, it provides limited insight into the protective nature of this immune response. Neutralizing antibodies recognizing the viral spike protein are more revealing, yet their measurement traditionally requires virus- and cell-based systems that are costly, time-consuming, inflexible, and potentially biohazardous. Here, we present a cell-free quantitative neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 spike protein binding to the angiotensin converting enzyme 2 (ACE2) receptor. This high-throughput method matches the performance of the gold standard live virus infection assay, as verified with a panel of 206 seropositive donors with varying degrees of infection severity and virus-specific IgG titers, achieving 96.7% sensitivity and 100% specificity. Furthermore, it allows for the parallel assessment of neutralizing activities against multiple SARS-CoV-2 spike protein variants of concern. We used our assay to profile serum samples from 59 patients hospitalized with coronavirus disease 2019 (COVID-19). We found that, although most sera had high activity against the 2019-nCoV parental spike protein and, to a lesser extent, the α (B.1.1.7) variant, only 58% of serum samples could efficiently neutralize a spike protein derivative containing mutations present in the β (B.1.351) variant. Thus, we have developed an assay that can evaluate effective neutralizing antibody responses to SARS-CoV-2 spike protein variants of concern after natural infection and that can be applied to characterize vaccine-induced antibody responses or to assess the potency of monoclonal antibodies.

scholarly journals High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

2016 ◽  
Vol 23 (8) ◽  
pp. 707-716 ◽  
Author(s):  
Sun B. Sowers ◽  
Jennifer S. Rota ◽  
Carole J. Hickman ◽  
Sara Mercader ◽  
Susan Redd ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Neutralizing Antibody ◽  
The United States ◽  
High Avidity ◽  
Serum Samples ◽  
Negative Results ◽  
High Concentrations

ABSTRACTIn the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml.

scholarly journals Immunogenicity in sheep of Uruguayan commercial vaccines against bovine alphaherpesvirus 1, 5 and bovine pestiviruses

2020 ◽  
Vol 50 (4) ◽  
Author(s):  
Ingryd Merchioratto ◽  
Alana de Almeida Aurélio ◽  
Janice Machado Villela ◽  
Nicole Vieira Stone ◽  
Isac Junior Roman ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Serological Response ◽  
Serum Samples ◽  
Post Vaccination ◽  
Immunological Responses ◽  
Antibody Titers ◽  
Low Levels

ABSTRACT: The serological responses induced by four commercial inactivated Uruguayan vaccines against bovine alphaherpesviruses (BoHV)-1 and -5 and bovine pestiviruses (BVDV-1, BVDV-2, and HoBiPeV) were evaluated in sheep. Thirty-seven sheep were immunized twice (day 0 and 25) and their serum samples were tested at different intervals (days 0, 25, 40, 60, and 90) post-vaccination (PV). Among the four vaccines tested, only one (G4) could induce the production of moderate neutralizing antibody titers against BoHV-1 and -5 and BVDV-1 and -2. The G3 vaccine showed a neutralizing serological response against the bovine alphaherpesviruses only. The G1 and G2 vaccines produced extremely low levels of antibodies in a few vaccinated animals only (geometric mean titers (GMT) 2.2). Similar levels of immunological responses were induced by the G4 vaccine against BoHV-1 and -5, and titers of neutralizing antibodies induced in approximately 70% of the animals are known to confer protection (GMT > 8). For bovine pestiviruses, the vaccine stimulated response of G4 against BVDV-2 was higher compared to that against BVDV-1, and extremely low for HoBiPeV. The peak of neutralizing antibodies to BoHV-1 and BVDV-1 was observed on days 40 and 60 PV, respectively. Thereafter, a remarkably decrease in neutralizing antibody response was observed at day 90 PV. These results demonstrated that tested commercial Uruguayan vaccines did not induce a serological response of adequate magnitude and duration. Thus, it is important to periodically review formulations and compositions of commercial vaccines against bovine alphaherpesviruses and pestiviruses.

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