antibody concentration
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Author(s):  
Tess E Altvater-Hughes ◽  
Douglas C Hodgins ◽  
Lauraine Wagter-Lesperance ◽  
Shannon C Beard ◽  
Shannon L Cartwright ◽  
...  

Abstract Immunoglobulin (Ig) G and natural antibody (NAb) IgM are passively transferred to the neonatal calf through bovine colostrum. Maternal IgG provides pathogen- or vaccine-specific protection and comprises about 85 percent of colostral Ig. Natural antibody IgM is less abundant but provides broad and non-specific reactivity, potentially contributing to protection against the dissemination of pathogens in the blood (septicemia) in a calf’s first days of life. In the dairy and beef industries, failure of passive transfer (FPT) of colostral Ig (serum total protein (STP) <5.2 g/dL) is still a common concern. The objectives of this study were to, i) compare colostral IgG concentrations and NAb-IgM titers between dairy and beef cows; ii) assess the effect of beef breed on colostral IgG; iii) compare passive transfer of colostral Ig in dairy and beef calves; and iv) estimate the heritability of colostral IgG and NAb-IgM. Colostrum was collected from Holstein dairy (n=282) and crossbred beef (n=168) cows at the University of Guelph dairy and beef research centres. Colostral IgG was quantified by radial immunodiffusion and NAb-IgM was quantified by an enzyme-linked immunosorbent assay. In dairy (n=308) and beef (n=169) calves, STP was estimated by digital refractometry. Beef cows had significantly greater colostral IgG (146.5 ± 9.5 SEM g/L) than dairy cows (92.4 ± 5.2 g/L, p <0.01). Beef cows with a higher proportion of Angus ancestry had significantly lower colostral IgG (125.5 ± 5.8 g/L) than cows grouped as “Other” (142.5 ± 4.9 g/L, p= 0.02). Using the FPT cut-off, 13% of dairy and 16% of beef calves had FPT; still, beef calves had a significantly larger proportion with excellent passive transfer (STP ≥6.2 g/dL, p <0.01). The heritability of colostral IgG was 0.04 (± 0.14) in dairy and 0.14 (± 0.32) in beef. Colostral NAb-IgM titers in dairy (12.12 ± 0.22, log2 (reciprocal of titer)) and beef cows (12.03 ± 0.19) did not differ significantly (p=0.71). The range of NAb-IgM titers was 9.18 to 14.60, equivalent to a 42-fold range in antibody concentration. The heritability of colostral NAb was 0.24 (± 0.16) in dairy and 0.11 (± 0.19) in beef cows. This study is the first to compare colostral NAb-IgM between dairy and beef cows. Based on the range in NAb-IgM titers and the heritability, selective breeding may improve colostrum quality and protection for neonatal calves in the early days of life.


2022 ◽  
Author(s):  
Kriangkrai Tawinprai ◽  
Taweegrit Siripongboonsitti ◽  
Thachanun Porntharukchareon ◽  
Preeda Vanichsetakul ◽  
Saraiorn Thonginnetra ◽  
...  

Introduction: COVID-19 pandemic affects all populations worldwide, including adolescents. Adolescents can develop a severe form of COVID-19, especially with comorbidity underlying. The prior studies of the mRNA COVID-19 vaccine showed excellent effectiveness in adolescents. Therefore, this study aimed to evaluate the safety and effectiveness of the BBIBP-CorV vaccine with the immunobridging approach in Thai adolescents. Methods: This single-center, prospective cohort study compared the immunogenicity after 2 doses of the BBIBO-CorV vaccine with 21 days interval of participants aged 12-17 years with 18-30 years at Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand. The key eligible criteria were healthy or had stable pre-existing comorbidity participants, aged 12-17 years. The primary endpoint was the anti-receptor binding domain antibody concentration at 4 weeks after dose 2 of the vaccine. In addition, safety profiles were solicited adverse events within 7 days after each dose of vaccine and any adverse events through 1 month after dose 2 of the vaccine. Results: Four weeks after the second vaccination, the GMC of anti-RBD antibody in the adolescent cohort was 102.9 BAU/mL (95%CI; 91.0-116.4) and 36.9 BAU/mL (95%CI; 30.9-44.0) in the adult cohort. The GMR of the adolescent cohort was 2.79 (95%CI; 2.25-3.46, p-value; <0.0001) compared with the adult cohort which met non-inferiority criteria. The reactogenicity was slightly less reported in the adolescent cohort compared with the adult cohort. No serious adverse events were reported in both cohorts. Conclusion: Vaccination with the BBIBP-CorV vaccine in the adolescent participants was safe and effective.


2021 ◽  
Author(s):  
Jasper de Boer ◽  
Ursula Saade ◽  
Elodie Granjon ◽  
Sophie Trouillet-Assant ◽  
Carla Saade ◽  
...  

Background: It is crucial for medical decision-making and vaccination strategies to collect information on sustainability of immune responses after infection or vaccination, and how long-lasting antibodies against SARS-COV-2 could provide a humoral and protective immunity, preventing reinfection with SARS-CoV-2 or its variants. The aim of this study is to present a novel method to quantitatively measure and monitor the diversity of SARS-CoV-2 specific antibody profiles over time. Methods: Two collections of serum samples were used in this study: A collection from 20 naturally-infected subjects (follow-ups to 1 year) and a collection from 83 subjects vaccinated with one or two doses of Pfizer BioNtech vaccine (BNT162b2/BNT162b2) (follow-ups to 6 months). The Multi-SARS-CoV-2 assay, a multiparameter serology test, developed for the serological confirmation of past-infections was used to determine the reactivity of six different SARS-CoV-2 antigens. For each patient sample, 3 dilutions (1/50, 1/400 and 1/3200) were defined as an optimal set over the six antigens and their respective linear ranges, allowing accurate quantitation of the corresponding six specific antibodies. Nonlinear mixed-effects modelling was applied to convert intensity readings from 3 determined dilutions to a single quantification value for each antibody. Results: Median half-life for the 20 naturally infected vs 74 vaccinated subjects (two doses) was respectively 120 vs 50 days for RBD, 127 vs 53 days for S1 and 187 vs 86 days for S2 antibodies. Respectively, 90% of the antibody concentration wanes after 158 vs 398 days for RBD, 171 vs 420 days for S1, and 225 vs 620 days for S2 after the second vaccine shot. Conclusion: The newly proposed method, based on a series of a limited number of dilutions, can convert a conventional qualitative assay into a quantitative assay. This conversion helps define the sustainability of specific immune responses against each relevant viral antigen and can help in defining the protection characteristics after an infection or a vaccination.


2021 ◽  
Author(s):  
Javier T. Garza ◽  
Jacob Quick ◽  
Dev Chatterjee ◽  
Robert Patrick Garr ◽  
Atul Varadhachary ◽  
...  

COVID-19 has affected billions of people around the world directly or indirectly. The response to the pandemic has focused on preventing the spread of the disease and improving treatment options. Diagnostic technologies have played a key role in this response since the beginning of the pandemic. As vaccines and other treatments have been developed and deployed, interest in understanding and measuring the individual level of immune protection has increased. Historically, use of antibody titers to measure systemic immunity has been constrained by an incomplete understanding of the relationship between antibodies and immunity, the lack of international standards for antibody concentration to enable cross-study comparisons, and insufficient clinical data to allow for the development of robust antibody-immunity models. However, these constraints have recently shifted. With a deeper understanding of antibodies, the promulgation of WHO antibody standards, and the development of immunity models using datasets from multiple COVID-19 vaccine trials, certain types of quantitative antibody tests may now provide a way to monitor individual or community immunity against COVID-19. Specifically, tests that quantitate the concentration of anti-RBD IgG -antibodies that target the receptor binding domain of the S1 spike protein component of the SARS-CoV-2 virus- show promise as a useful and scalable measure of the COVID-19 immunity of both individuals and communities. However, to fulfill this promise, a rapid and easy-to-administer test is needed. To address this important clinical need, Brevitest deployed its point-of-care-capable technology platform that can run a rapid (<15 minute), quantitative antibody test with a sample of 10 µl of whole blood from a fingerstick. The test we validated on this platform measures the concentration of anti-RBD IgG in Binding Antibody Units per milliliter (BAU/mL) per WHO Reference Standard NIBSC 20/136. In this paper, we present studies used to characterize the Brevitest anti-RBD IgG assay and evaluate its clinical performance, lower limits of measurement, precision, linearity, interference, and cross-reactivity. The results demonstrate the ability of this assay to measure a patient's anti-RBD IgG concentration. This information, together with models developed from recent COVID-19 vaccine clinical trials, can provide a means of assessing the current level of immune protection of an individual or community against COVID-19 infection.


2021 ◽  
Author(s):  
Prateek Singh ◽  
Rajat Ujjainiya ◽  
Satyartha Prakash ◽  
Salwa Naushin ◽  
Viren Sardana ◽  
...  

Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the effectiveness of interventions. Asymptomatic breakthrough infections have been a major problem during the ongoing surge of Delta variant globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines used in the higher-income regions. Here, we show for the first time how statistical and machine learning (ML) approaches can discriminate SARS-CoV-2 infection from immune response to an inactivated whole virion vaccine (BBV152, Covaxin, India), thereby permitting real-world vaccine effectiveness assessments from cohort-based serosurveys in Asia and Africa where such vaccines are commonly used. Briefly, we accessed serial data on Anti-S and Anti-NC antibody concentration values, along with age, sex, number of doses, and number of days since the last vaccine dose for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine (SVM) model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, 724 were classified as infected. Since the vaccine contains wild-type virus and the antibodies induced will neutralize wild type much better than Delta variant, we determined the relative ability of a random subset of such samples to neutralize Delta versus wild type strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, Delta variant, was neutralized more effectively than the wild type, which cannot happen without infection. The fraction rose to 71.8% (28 of 39) in subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period.


2021 ◽  
Author(s):  
David E Williams

Abstract The empirically-observed dependence on blood IgG anti-receptor binding domain antibody concentration of SARS-CoV-2 vaccine efficacy against infection has a rational explanation in the statistics of binding of antibody to spike proteins on the virus surface: namely that the probability of protection is the probability of antibody binding to more than a critical number of the spike proteins protruding from the virus. The model is consistent with the observed antibody concentrations required to induce immunity and with the observed dependence of vaccine efficacy on antibody concentration and thus is a useful tool in the development of models to relate, for an individual person, risk of breakthrough infection given measured antibody concentration


2021 ◽  
Vol 15 (12) ◽  
pp. e0010017
Author(s):  
Lisa Hefele ◽  
Antony P. Black ◽  
Trinh Van Tan ◽  
Nguyen Tri Minh ◽  
Nguyen Duc Hoang ◽  
...  

The epidemiology of typhoid fever in Lao People`s Democratic Republic is poorly defined. Estimating the burden of typhoid fever in endemic countries is complex due to the cost and limitations of population-based surveillance; serological approaches may be a more cost-effective alternative. ELISAs were performed on 937 serum samples (317 children and 620 adults) from across Lao PDR to measure IgG antibody titers against Vi polysaccharide and the experimental protein antigens, CdtB and HlyE. We measured the significance of the differences between antibody titers in adults and children and fitted models to assess the relationship between age and antibody titers. The median IgG titres of both anti-HylE and CdtB were significantly higher in children compared to adults (anti-HylE; 351.7 ELISA Units (EU) vs 198.1 EU, respectively; p<0.0001 and anti-CdtB; 52.6 vs 12.9 EU; p<0.0001). Conversely, the median anti-Vi IgG titer was significantly higher in adults than children (11.3 vs 3.0 U/ml; p<0.0001). A non-linear trend line fitted to the anti-CdtB and anti-HlyE IgG data identified a peak in antibody concentration in children <5 years of age. We identified elevated titers of anti-HlyE and anti-CdtB IgG in the serum of children residing in Lao PDR in comparison to adults. These antigens are associated with seroconversion after typhoid fever and may be a superior measure of disease burden than anti-Vi IgG. This approach is scalable and may be developed to assess the burden of typhoid fever in countries where the disease may be endemic, and evidence is required for the introduction of typhoid vaccines.


2021 ◽  
Author(s):  
Matheus J. T. Vargas ◽  
Mithileshwari Chandrasekhar ◽  
Yong Je Kwon ◽  
Gerrit Sjoerd Deijs ◽  
Carsten Ma On Wong Corazza ◽  
...  

AbstractWe show that an individual’s immune status to Covid-19 can be monitored through quantitative antibody measurements using a method specifically designed for high throughput and accuracy from a finger-prick blood sample. The quality of the rapid test results is comparable to that from major commercial laboratory testing kits. Anti-Receptor Binding Domain (RBD) IgG concentration showed a log-normal distribution with mean decreasing with time following the second vaccination with mRNA BNT162b2 (Pfizer). Using a model for an individual’s antibody concentration-dependent vaccine efficacy allowed comparison with literature data on changing vaccine efficacy against symptomatic disease across a population. In this small trial (n = 100) estimated median vaccine efficacy was 90% (range 65-95%) < 90 days post vaccination, 75% (range 35 – 90%) 90 – 170 days and 65% (range 35-90%) 170 – 230 days. The results provide strong support for personalized booster programmes that, by targeting people in the tail of the distribution, should be more effective at diminishing breakthrough infection and optimising booster dose supply than a program that simply mandates a booster at a specific post-vaccination time point.


Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2216
Author(s):  
Rosana Wing-Shan Poon ◽  
Lu Lu ◽  
Carol Ho-Yan Fong ◽  
Tak-Chuen Ip ◽  
Lin-Lei Chen ◽  
...  

Objectives: The emergence of SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of vaccines and are associated with a rebound in the number of COVID-19 cases globally. These variants contain mutations at the spike (S) protein receptor binding site (RBD), which affect antibody binding. Current commercially available antibody assays were developed before the VOCs emerged. It is unclear whether the levels of these commercially available antibody assays can predict the neutralizing antibody titers against the VOCs. In this study, we sought to determine the correlation between the binding antibody concentration and microneutralization antibody titer against the beta variant. Methods: This study included 58 COVID-19 patients. The concentrations of IgG against the SARS-CoV-2 spike protein RBD and nucleocapsid (N) protein were measured using the Abbott SARS-CoV-2 IgG II Quant assay and the SARS-CoV-2 IgG assay, respectively. The neutralization antibody titer against the wild type lineage A SARS-CoV-2 and against the beta variant (B.1.351) was determined using a conventional live virus neutralization test. Results: The geometric mean MN titer (GMT) against the beta variant was significantly lower than that against the wild type lineage A virus (5.6 vs. 47.3, P<0.0001). The anti-RBD IgG had a better correlation with the neutralizing antibody titer than that of the anti-N IgG assay against the wild type lineage A virus (Spearman rho, 0.5901 vs. 0.3827). However, the correlation between the anti-RBD or the anti-N IgG and the MN titer against the beta variant was poor. Conclusions: Currently available commercial antibody assays may not predict the level of neutralizing antibodies against the variants. A new generation of antibody tests specific for variants are required.


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