scholarly journals Sustained Neutralizing Antibodies 6 Months Following Infection in 376 Japanese COVID-19 Survivors

2021 ◽  
Vol 12 ◽  
Author(s):  
Atsushi Goto ◽  
Hirofumi Go ◽  
Kei Miyakawa ◽  
Yutaro Yamaoka ◽  
Norihisa Ohtake ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Test Results ◽  
Serum Samples ◽  
Factors Associated ◽  
Antibody Titers ◽  
Spearman’S Correlation

Objective: There is scarce evidence regarding the long-term persistence of neutralizing antibodies among coronavirus disease 2019 (COVID-19) survivors. This study determined neutralizing antibody titers (NT50) and antibodies against spike protein (SP) or nucleocapsid protein (NP) antigens approximately 6 months after the diagnosis of COVID-19.Methods: COVID-19 survivors in Japan were recruited. Serum samples and data related to patients’ characteristics and COVID-19 history were collected. NT50 and titers of antibodies against NP and SP antigens were measured at 20–32 weeks after the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results. Factors associated with NT50 were identified using the multivariable linear regression and the correlations among NT50 and titers of immunoglobulin G (IgG) and total immunoglobulins (Igs) against NP and SP were assessed by Spearman’s correlation.Results: Among 376 participants (median [range] days after testing positive for SARS-CoV-2, 180 (147–224); median [range] years of age, 50 (20–78); 188 [50%] male), most tested positive for NT50 (n = 367, 98%), SP-IgG (n = 344, 91%), SP-total Ig (n = 369, 98%), NP-IgG (n = 314, 84%), and NP-total Ig (n = 365, 97%). Regression analysis indicated that higher BMI, fever, and the requirement of mechanical ventilation or extracorporeal membrane oxygenation were significantly associated with higher NT50. Anti-SP antibodies correlated moderately with NT50 (Spearman’s correlation: 0.63 for SP IgG; 0.57 for SP-total Ig), while the correlation was weak for anti-NP antibodies (0.37 for NP IgG; 0.32 for NP-total Ig).Conclusions: Most COVID-19 survivors had sustained neutralizing antibodies and tested positive for SP-total Ig and NP-total Ig approximately 6 months after infection.

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 Severe Acute Respiratory Syndrome-Associated Coronavirus Vaccines Formulated with Delta Inulin Adjuvants Provide Enhanced Protection while Ameliorating Lung Eosinophilic Immunopathology

2014 ◽  
Vol 89 (6) ◽  
pp. 2995-3007 ◽  
Author(s):  
Yoshikazu Honda-Okubo ◽  
Dale Barnard ◽  
Chun Hao Ong ◽  
Bi-Hung Peng ◽  
Chien-Te Kent Tseng ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Case Fatality ◽  
Neutralizing Antibody ◽  
The Elderly ◽  
Spike Protein ◽  
Interleukin 4 ◽  
Unique Problem ◽  
Antibody Titers ◽  
Ifn Γ

ABSTRACTAlthough the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) epidemic was controlled by nonvaccine measures, coronaviruses remain a major threat to human health. The design of optimal coronavirus vaccines therefore remains a priority. Such vaccines present major challenges: coronavirus immunity often wanes rapidly, individuals needing to be protected include the elderly, and vaccines may exacerbate rather than prevent coronavirus lung immunopathology. To address these issues, we compared in a murine model a range of recombinant spike protein or inactivated whole-virus vaccine candidates alone or adjuvanted with either alum, CpG, or Advax, a new delta inulin-based polysaccharide adjuvant. While all vaccines protected against lethal infection, addition of adjuvant significantly increased serum neutralizing-antibody titers and reduced lung virus titers on day 3 postchallenge. Whereas unadjuvanted or alum-formulated vaccines were associated with significantly increased lung eosinophilic immunopathology on day 6 postchallenge, this was not seen in mice immunized with vaccines formulated with delta inulin adjuvant. Protection against eosinophilic immunopathology by vaccines containing delta inulin adjuvants correlated better with enhanced T-cell gamma interferon (IFN-γ) recall responses rather than reduced interleukin-4 (IL-4) responses, suggesting that immunopathology predominantly reflects an inadequate vaccine-induced Th1 response. This study highlights the critical importance for development of effective and safe coronavirus vaccines of selection of adjuvants based on the ability to induce durable IFN-γ responses.IMPORTANCECoronaviruses such as SARS-CoV and Middle East respiratory syndrome-associated coronavirus (MERS-CoV) cause high case fatality rates and remain major human public health threats, creating a need for effective vaccines. While coronavirus antigens that induce protective neutralizing antibodies have been identified, coronavirus vaccines present a unique problem in that immunized individuals when infected by virus can develop lung eosinophilic pathology, a problem that is further exacerbated by the formulation of SARS-CoV vaccines with alum adjuvants. This study shows that formulation of SARS-CoV spike protein or inactivated whole-virus vaccines with novel delta inulin-based polysaccharide adjuvants enhances neutralizing-antibody titers and protection against clinical disease but at the same time also protects against development of lung eosinophilic immunopathology. It also shows that immunity achieved with delta inulin adjuvants is long-lived, thereby overcoming the natural tendency for rapidly waning coronavirus immunity. Thus, delta inulin adjuvants may offer a unique ability to develop safer and more effective coronavirus vaccines.

Neutralizing antibody titers six months after Comirnaty vaccination: kinetics and comparison with SARS-CoV-2 immunoassays

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrea Padoan ◽  
Chiara Cosma ◽  
Francesco Bonfante ◽  
Foscarina della Rocca ◽  
Francesco Barbaro ◽  
...  
Keyword(s):  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
University Hospital ◽  
Serum Samples ◽  
Viral Neutralization ◽  
Previous Infection ◽  
Antibody Titers ◽  
Males And Females ◽  
Antibody Levels

Abstract Objectives mRNA vaccines, including Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer), elicit high IgG and neutralizing antibody (NAb) responses after the second dose, but the progressive decrease in serum antibodies against SARS-CoV-2 following vaccination have raised questions concerning long-term immunity, decreased antibody levels being associated with breakthrough infections after vaccination, prompting the consideration of booster doses. Methods A total number of 189 Padua University-Hospital healthcare workers (HCW) who had received a second vaccine dose were asked to collect serum samples for determining Ab at 12 (t12) and 28 (t28) days, and 6 months (t6m) after their first Comirnaty/BNT162b2 inoculation. Ab titers were measured with plaque reduction neutralization test (PRNT), and three chemiluminescent immunoassays, targeting the receptor binding domain (RBD), the trimeric Spike protein (trimeric-S), and surrogate viral neutralization tests (sVNT). Results The median percentages (interquartile range) for decrease in antibodies values 6 months after the first dose were 86.8% (67.1–92.8%) for S-RBD IgG, 82% (58.6–89.3%) for trimeric-S, 70.4% (34.5–86.4%) for VNT-Nab, 75% (50–87.5%) for PRNT50 and 75% (50–93.7%) for PRNT90. At 6 months, neither PRNT titers nor VNT-Nab and S-RBD IgG bAb levels correlated with age (p=0.078) or gender (p=0.938), while they were correlated with previous infection (p<0.001). Conclusions After 6 months, a method-independent reduction of around 90% in anti-SARS-CoV-2 antibodies was detected, while no significant differences were found between values of males and females aged between 24 and 65 years without compromised health status. Further efforts to improve analytical harmonization and standardization are needed.

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 Development and Validation of an Assay To Detect Porcine Reproductive and Respiratory Syndrome Virus-Specific Neutralizing Antibody Titers in Pig Oral Fluid Samples

2013 ◽  
Vol 20 (8) ◽  
pp. 1305-1313 ◽  
Author(s):  
Kang Ouyang ◽  
Basavaraj Binjawadagi ◽  
Apisit Kittawornrat ◽  
Chris Olsen ◽  
Jagadish Hiremath ◽  
...  
Keyword(s):  
Disease Surveillance ◽  
Neutralizing Antibodies ◽  
Oral Fluid ◽  
Low Cost ◽  
Herd Immunity ◽  
Neutralizing Antibody ◽  
Respiratory Syndrome Virus ◽  
Serum Samples ◽  
Antibody Titers ◽  
Breeding Farms

ABSTRACTPorcine reproductive and respiratory syndrome virus (PRRSV)-specific neutralizing antibodies (NA) are important for clearing the virus. Pen-based pig oral fluid samples for disease surveillance are gaining in importance due to the ease of collection and low cost. The aim of this study was to develop a PRRSV-specific NA assay to determine NA titers in pig oral fluid samples. At first, we standardized the PRRSV NA assay using pen-based pig oral fluid samples collected over a period of 3 months from a herd of swine that received a PRRSV modified live vaccine (PRRS-MLV), and we also used oral fluid and serum samples collected from individual boars that were vaccinated with PRRS-MLV or infected with a virulent PRRSV strain. Our results suggest that a PRRSV NA titer of >8 in oral fluid samples is virus specific and can be detected beginning at 28 days after vaccination or infection. To validate the assay, we used 104 pen-based pig oral fluid and five representative serum samples from each pen of unknown history, as well as 100 serum samples from repeatedly vaccinated sows and oral fluid samples of their respective litters belonging to four different swine-breeding farms. Our results demonstrated that PRRSV NA titers in oral fluid samples are correlated with serum sample titers, and maternally derived PRRSV-specific NA titers could be detected in litters at the time of weaning. In conclusion, we have standardized and validated the pig oral fluid-based PRRSV NA assay, which has 94.3% specificity and 90.5% repeatability. The assay can be used to monitor herd immunity against PRRSV in vaccinated and infected herds of swine.

scholarly journals Antibodies against rabies virus in dogs with and without history of vaccination in Santa Maria - RS - Brazil

2017 ◽  
Vol 47 (11) ◽  
Author(s):  
Karina Gonzalez Fernandes ◽  
Mathias Martins ◽  
Bruna Portolan Amaral ◽  
Juliana Felipetto Cargnelutti ◽  
Rudi Weiblen ◽  
...  
Keyword(s):  
Rabies Virus ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
World Health ◽  
Serum Samples ◽  
Antibody Titers ◽  
Group A ◽  
Group B ◽  
Santa Maria ◽  
Rabies Vaccination

ABSTRACT: The present study investigated the frequency and magnitude of neutralizing antibodies to rabies virus (RABV) in dogs with and without historic of vaccination in Santa Maria/RS. Group A included serum samples from 440 dogs with recent historic of vaccination against rabies, obtained during the 2015 rabies vaccination campaign. Group B included 300 serum samples from dogs submitted to the Veterinary Hospital of the Universidade Federal de Santa Maria in 2015, whose historic of rabies vaccination was unknown. Serum samples were submitted to the rapid fluorescent focus inhibition test (RFFIT) to detect neutralizing antibodies against RABV. In group A, 70.6% (310/440) of the samples had neutralizing antibody titers ≥0.5 international units per milliliter (IU mL-1), considered an indicative of protection against rabies by the World Health Organization. However, approximately 30% of the dogs did not contain antibodies in adequate levels. In group B, 42.3% (127/300) of the samples contained neutralizing antibody titers ≥0.5IU mL-1 and 57.7% (173/300) were negative or contained titers below of the value considered immunized. These results demonstrate that an important proportion of vaccinated dogs (~30%) did not develop adequate antibody levels, mainly those receiving a single vaccine dose. Serologic testing of animals with unknown historic of vaccination revealed relatively low vaccine coverage in the general dog population. Thus, reformulation of immunization strategies - especially the recommendation of a boost vaccination 30 days after the primary dose - and extension of vaccination campaigns are necessary to reach adequate levels and coverage of immunity against RABV in the canine population.

scholarly journals Dynamics of neutralizing antibody titers in the months after SARS-CoV-2 infection

2020 ◽  
Author(s):  
Katharine HD Crawford ◽  
Adam S Dingens ◽  
Rachel Eguia ◽  
Caitlin R Wolf ◽  
Naomi Wilcox ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Early Immune Response ◽  
Antibody Titers ◽  
Antibody Levels ◽  
Time Frames ◽  
Initial Peak

Most individuals infected with SARS-CoV-2 develop neutralizing antibodies that target the viral spike protein. Here we quantify how levels of these antibodies change in the months following SARS-CoV-2 infection by examining longitudinal samples collected between ≈30 and 152 days post-symptom onset from a prospective cohort of 34 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about four-fold from one to four months post-symptom onset. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B-cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.

scholarly journals Comparative quantitative analysis of SARS-CoV-2 Spike neutralizing antibody titers following two anti COVID-19 vaccines in India

2021 ◽  
Author(s):  
Chanukya GV ◽  
Aparna Srikantam
Keyword(s):  
Quantitative Analysis ◽  
Neutralizing Antibodies ◽  
Large Scale ◽  
Neutralizing Antibody ◽  
Long Term Follow Up ◽  
Antibody Titers ◽  
Age Studies ◽  
Immunogenic Response

In COVID 19 pandemic, first line of defense is effective vaccination program. Because of multiple platforms available for vaccine production we tested relative immunogenicity of two vaccines available in India, Covaxin and Covishield We performed quantitative analysis of neutralizing antibodies to SARS Cov2 spike (receptor binding domain ) protein, from sera of 53 subjects who completed vaccines schedules. There was significantly higher immunogenic response with Covishield as compared to Covaxin and are independent of age. Studies on a large scale with long term follow up are needed to further advance the knowledge in this domain.

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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