scholarly journals Serum Immunoglobulin A Cross-Strain Blockade of Human Noroviruses

2015 ◽  
Vol 2 (3) ◽  
Author(s):  
Lisa C. Lindesmith ◽  
Martina Beltramello ◽  
Jesica Swanstrom ◽  
Taylor A. Jones ◽  
Davide Corti ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Vaccine Development ◽  
Immunoglobulin A ◽  
Neutralization Assay ◽  
Viral Gastroenteritis ◽  
Human Noroviruses ◽  
Serum Iga ◽  
Multiple Virus ◽  
Antibody Titers ◽  
Carbohydrate Ligands

Abstract Background.  Human noroviruses are the leading cause of acute viral gastroenteritis, justifying vaccine development despite a limited understanding of strain immunity. After genogroup I (GI).1 norovirus infection and immunization, blockade antibody titers to multiple virus-like particles (VLPs) increase, suggesting that GI cross-protection may occur. Methods.  Immunoglobulin (Ig)A was purified from sera collected from GI.1-infected participants, and potential neutralization activity was measured using a surrogate neutralization assay based on antibody blockade of ligand binding. Human and mouse monoclonal antibodies (mAbs) were produced to multiple GI VLPs to characterize GI epitopes. Results.  Immunoglobulin A purified from day 14 post-GI.1 challenge sera blocked binding of GI.1, GI.3, and GI.4 to carbohydrate ligands. In some subjects, purified IgA preferentially blocked binding of other GI VLPs compared with GI.1, supporting observations that the immune response to GI.1 infection may be influenced by pre-exposure history. For other subjects, IgA equivalently blocked multiple GI VLPs. Only strain-specific mAbs recognized blockade epitopes, whereas strain cross-reactive mAbs recognized nonblockade epitopes. Conclusions.  These studies are the first to describe a functional role for serum IgA in norovirus immunity and the first to characterize human monoclonal antibodies to GI strains, expanding our understanding of norovirus immunobiology.

scholarly journals IgA: Structure, Function, and Developability

Antibodies ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 57 ◽  
Author(s):  
Patrícia de Sousa-Pereira ◽  
Jenny M. Woof
Keyword(s):  
Monoclonal Antibodies ◽  
Structure Function ◽  
Immunoglobulin A ◽  
Structural Features ◽  
The Other ◽  
Immune Defence ◽  
Major Site ◽  
Mucosal Surfaces ◽  
Serum Iga ◽  
Antibody Class

Immunoglobulin A (IgA) plays a key role in defending mucosal surfaces against attack by infectious microorganisms. Such sites present a major site of susceptibility due to their vast surface area and their constant exposure to ingested and inhaled material. The importance of IgA to effective immune defence is signalled by the fact that more IgA is produced than all the other immunoglobulin classes combined. Indeed, IgA is not just the most prevalent antibody class at mucosal sites, but is also present at significant concentrations in serum. The unique structural features of the IgA heavy chain allow IgA to polymerise, resulting in mainly dimeric forms, along with some higher polymers, in secretions. Both serum IgA, which is principally monomeric, and secretory forms of IgA are capable of neutralising and removing pathogens through a range of mechanisms, including triggering the IgA Fc receptor known as FcαRI or CD89 on phagocytes. The effectiveness of these elimination processes is highlighted by the fact that various pathogens have evolved mechanisms to thwart such IgA-mediated clearance. As the structure–function relationships governing the varied capabilities of this immunoglobulin class come into increasingly clear focus, and means to circumvent any inherent limitations are developed, IgA-based monoclonal antibodies are set to emerge as new and potent options in the therapeutic arena.

scholarly journals Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman primates

2020 ◽  
Author(s):  
Wenlin Ren ◽  
Hunter Sun ◽  
George F. Gao ◽  
Jianxin Chen ◽  
Sean Sun ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Vaccine Development ◽  
Neutralization Assay ◽  
List Type ◽  
Potential Candidate ◽  
Live Virus ◽  
Global Pandemic ◽  
Fc Fusion Protein ◽  
Antibody Titers ◽  
Strong Candidate

AbstractThe COVID-19 outbreak has become a global pandemic responsible for over 2,000,000 confirmed cases and over 126,000 deaths worldwide. In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. We demonstrate that the S1-Fc fusion protein is extremely immunogenic, as evidenced by strong antibody titers observed by day 7. Strong virus neutralizing activity was observed on day 14 in rabbits immunized with the S1-Fc fusion protein using a pseudovirus neutralization assay. Most importantly, in less than 20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. Our data strongly suggests that the CHO-expressed SARS-CoV-2 S1-Fc recombinant protein could be a strong candidate for vaccine development against COVID-19.HighlightsCHO-expressed S1-Fc protein is very immunogenic in various animals and can rapidly induce strong antibody productionS1-Fc protein solicits strong neutralizing activities against live virusStable CHO cell line expressing 50 mg/L of S1-Fc and a 3,000 L Bioreactor can produce 3 million doses of human COVID-19 vaccine every 10 days, making it an accessible and affordable option for worldwide vaccination

scholarly journals A Neutralization Assay Based on Pseudo-Typed Lentivirus with SARS CoV-2 Spike Protein in ACE2-Expressing CRFK Cells

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 153
Author(s):  
Yalçın Pısıl ◽  
Hisatoshi Shida ◽  
Tomoyuki Miura
Keyword(s):  
Monoclonal Antibodies ◽  
Inhibitory Concentration ◽  
Immunoglobulin A ◽  
Hek293t Cell ◽  
Neutralization Assay ◽  
Cell System ◽  
Immunoglobulin M ◽  
Spike Protein ◽  
Highly Pathogenic ◽  
Angiotensin Converting Enzyme 2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic zoonotic virus that spreads rapidly. In this work, we improve the hitherto existing neutralization assay system to assess SARS-CoV-2 inhibitors using a pseudo-typed lentivirus coated with the SARS-CoV-2 spike protein (LpVspike +) and angiotensin-converting enzyme 2 (ACE2)-transfected cat Crandell–Rees feline kidney (CRFK) cells as the host cell line. Our method was 10-fold more sensitive compared to the typical human embryonic kidney 293T (HEK293T) cell system, and it was successfully applied to quantify the titers of convalescent antisera and monoclonal anti-spike antibodies required for pseudo virus neutralization. The 50% inhibition dilution (ID50) of two human convalescent sera, SARS-CoV-2 immunoglobulin G (IgG) and SARS-CoV-2 immunoglobulin M (IgM), which were 1:350 (±1:20) and 1:1250 (±1:350), respectively. The 50% inhibitory concentration (IC50) of the IgG, IgM and immunoglobulin A (IgA) anti-SARS-CoV-2 monoclonal antibodies (mAbs) against LpVspike(+) were 0.45 (±0.1), 0.002 (±0.001) and 0.004 (±0.001) µg mL−1, respectively. We also found that reagents typically used to enhance infection were not effective in the CFRK system. This methodology is both efficient and safe; it can be employed by researchers to evaluate neutralizing monoclonal antibodies and contribute to the discovery of new antiviral inhibitors against SARS-CoV-2.

The effect of probiotics on the level of immunoglobulin A in women with violation of the biocenosis of the vagina

2017 ◽  
pp. 85-88
Author(s):  
O.I. Ostapenko ◽  
◽  
V.P. Kvashenko ◽  
I.K. Akimova ◽  
I.N. Nosova ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
Lactobacillus Rhamnosus ◽  
Test System ◽  
Main Group ◽  
Reproductive Age ◽  
Local Action ◽  
Serum Immunoglobulin ◽  
Control Group ◽  
Local Immunity ◽  
Serum Iga

The objective: the study of immunomodulatory effects of a probiotic, which contains lyophilized Lactobacillus (Lactobacillus rhamnosus) – 13 mg (2,0ґ109 CFU) and lyophilized bifidobacteria (Bifidobacterium lactis) – 4 mg (2,0ґ109 CFU) the level of serum immunoglobulin IgA as a marker of local immunity in the plasma of women of reproductive age with the violation of the biocenosis of the vagina. Patients and methods. The study involved 86 patients of reproductive age with the violation of the vaginal biocenosis, which were divided into two groups according to received treatment. A survey was conducted for all patients in both groups: determine the level of serum IgA, measuring pH of vaginal environment and the quantification of lactobacilli and pathogenic flora with the help of test-system «Florotsenoz» before treatment and in 6 weeks after treatment. The state of vaginal microbiocenosis in both groups before treatment was homogeneous. Patients in both groups as therapy at the first stage of treatment received, if necessary antimicrobial therapy depending on the selected flora. In the second stage (restoration of microflora) patient of the main group received systemic probiotic combined with a complex prebiotic local action, patients in the control group, the probiotic localy in the form of the vaginal candles or tablets. Results. The research stated the increasing level of serum IgA in blood plasma of patients of the main group compared to control group at 20%, normalizing the pH of the vaginal environment in the main group in 94% of cases, which indicates an increase of immunity in mucosal. Conclusion. The inclusion of the systemic probiotic in the scheme of treatment of disorders of biocenosis of the vagina system enhances the increasing of immunity of the mucous membranes, and the vaginal tablets prebiotic of local action restores the own normal microflora of the vagina. Key words: serum immunoglobulin A, local immunity, vaginal dysbiosis, probiotics, prebiotics, vaginal microbiocenosis, the pH of the vaginal environment.

scholarly journals Towards Quantitative and Standardized Serological and Neutralization Assays for COVID-19

2021 ◽  
Vol 22 (5) ◽  
pp. 2723
Author(s):  
Linhua Tian ◽  
Elzafir B. Elsheikh ◽  
Paul N. Patrone ◽  
Anthony J. Kearsley ◽  
Adolfas K. Gaigalas ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Epidemiologic Studies ◽  
Cross Reactivity ◽  
Receptor Binding Domain ◽  
Proof Of Concept ◽  
Reference Standard ◽  
Improve Measurement ◽  
Antibody Titers

Quantitative and robust serology assays are critical measurements underpinning global COVID-19 response to diagnostic, surveillance, and vaccine development. Here, we report a proof-of-concept approach for the development of quantitative, multiplexed flow cytometry-based serological and neutralization assays. The serology assays test the IgG and IgM against both the full-length spike antigens and the receptor binding domain (RBD) of the spike antigen. Benchmarking against an RBD-specific SARS-CoV IgG reference standard, the anti-SARS-CoV-2 RBD antibody titer was quantified in the range of 37.6 µg/mL to 31.0 ng/mL. The quantitative assays are highly specific with no correlative cross-reactivity with the spike proteins of MERS, SARS1, OC43 and HKU1 viruses. We further demonstrated good correlation between anti-RBD antibody titers and neutralizing antibody titers. The suite of serology and neutralization assays help to improve measurement confidence and are complementary and foundational for clinical and epidemiologic studies.

scholarly journals Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 284
Author(s):  
Hulda R. Jonsdottir ◽  
Michel Bielecki ◽  
Denise Siegrist ◽  
Thomas W. Buehrer ◽  
Roland Züst ◽  
...  
Keyword(s):  
Young Adults ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Asymptomatic Infection ◽  
Homogeneous Population ◽  
Humoral Immune ◽  
Antibody Titers

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

scholarly journals Poliovirus Sabin type 1 neutralization epitopes recognized by immunoglobulin A monoclonal antibodies.

1997 ◽  
Vol 71 (9) ◽  
pp. 6905-6912 ◽  
Author(s):  
L Fiore ◽  
B Ridolfi ◽  
D Genovese ◽  
G Buttinelli ◽  
S Lucioli ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Immunoglobulin A

scholarly journals Scalable, Micro-Neutralization Assay for Qualitative Assessment of SARS-CoV-2 (COVID-19) Virus-Neutralizing Antibodies in Human Clinical Samples

2021 ◽  
Author(s):  
Richard S. Bennett ◽  
Elena N. Postnikova ◽  
Janie Liang ◽  
Robin Gross ◽  
Steven Mazur ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Imaging System ◽  
Neutralization Assay ◽  
Qualitative Assessment ◽  
Clinical Samples ◽  
Therapeutic Approaches ◽  
Serum Samples ◽  
Specific Test ◽  
Multiple Virus ◽  
Infected Cells

AbstractAs the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic was expanding, it was clear that effective testing for the presence of neutralizing antibodies in the blood of convalescent patients would be critical for development of plasma-based therapeutic approaches. To address the need for a high-quality neutralization assay against SARS-CoV-2, a previously established fluorescence reduction neutralization assay (FRNA) against Middle East respiratory syndrome coronavirus (MERS-CoV) was modified and optimized. The SARS-CoV-2 FRNA provides a quantitative assessment of a large number of infected cells through use of a high-content imaging system. Because of this approach, and the fact that it does not involve subjective interpretation, this assay is more efficient and more accurate than other neutralization assays. In addition, the ability to set robust acceptance criteria for individual plates and specific test wells provided further rigor to this assay. Such agile adaptability avails use with multiple virus variants. By February 2021, the SARS-CoV-2 FRNA had been used to screen over 5,000 samples, including acute and convalescent plasma or serum samples and therapeutic antibody treatments, for SARS-CoV-2 neutralizing titers.

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.

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