scholarly journals Novel Neutralizing Epitope of PEDV S1 Protein Identified by IgM Monoclonal Antibody

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 125
Author(s):  
Techit Thavorasak ◽  
Monrat Chulanetra ◽  
Kittirat Glab-ampai ◽  
Karsidete Teeranitayatarn ◽  
Thaweesak Songserm ◽  
...  
Keyword(s):  
Passive Immunization ◽  
Neutralizing Antibody ◽  
Economic Damage ◽  
The Novel ◽  
Neutralizing Epitope ◽  
Swine Industry ◽  
Multiple Sequence ◽  
Diarrhea Virus ◽  
Reduction Assay ◽  
Infected Cells

Porcine epidemic diarrhea virus (PEDV) causes devastating enteric disease that inflicts huge economic damage on the swine industry worldwide. A safe and highly effective PEDV vaccine that contains only the virus-neutralizing epitopes (not enhancing epitope), as well as a ready-to-use PEDV neutralizing antibody for the passive immunization of PEDV vulnerable piglets (during the first week of life) are needed, particularly for PEDV-endemic farms. In this study, we generated monoclonal antibodies (mAbs) to the recombinant S1 domain of PEDV spike (S) protein and tested their PEDV neutralizing activity by CPE-reduction assay. The mAb secreted by one hybrodoma clone (A3), that also bound to the native S1 counterpart from PEDV-infected cells (tested by combined co-immunoprecipitation and Western blotting), neutralized PEDV infectivity. Epitope of the neutralizing mAb (mAbA3) locates in the S1A subdomain of the spike protein, as identified by phage mimotope search and multiple sequence alignment, and peptide binding-ELISA. The newly identified epitope is shared by PEDV G1 and G2 strains and other alphacoronaviruses. In summary, mAbA3 may be useful as a ready-to-use antibody for passive immunization of PEDV-susceptible piglets, while the novel neutralizing epitope, together with other, previously known protective epitopes, have potential as an immunogenic cocktail for a safe, next-generation PEDV vaccine.

scholarly journals Detection of porcine epidemic diarrhea virus–neutralizing antibody using high-throughput imaging cytometry

2020 ◽  
Vol 32 (2) ◽  
pp. 324-328
Author(s):  
Luciana V. Sarmento ◽  
Korakrit Poonsuk ◽  
Liying Tian ◽  
Juan C. Mora-Díaz ◽  
Rodger G. Main ◽  
...  
Keyword(s):  
High Throughput ◽  
Porcine Epidemic Diarrhea Virus ◽  
Herd Immunity ◽  
Neutralizing Antibody ◽  
Serum Samples ◽  
Swine Industry ◽  
Diarrhea Virus ◽  
Long Term Storage ◽  
Imaging Cytometry ◽  
Porcine Epidemic Diarrhea

Porcine epidemic diarrhea virus (PEDV) is an emerging porcine coronavirus that causes a tremendous economic burden on the swine industry. The assessment of PEDV-neutralizing antibody levels provides a valuable tool to assess and predict herd immunity. We evaluated the performance of a PEDV imaging cytometry–based high-throughput neutralization test (HTNT) and compared the HTNT to a fluorescent focus neutralization (FFN) assay using serum samples from pigs of known PEDV infection status ( n = 159). Estimates of diagnostic sensitivity and specificity for HTNT and FFN assays derived from receiver-operator characteristic (ROC) curve analyses showed that both PEDV FFN and HTNT provided excellent diagnostic performance. However, in the laboratory, imaging cytometry provided an objective and semi-automated approach that removed human subjectivity from the testing process and reduced the read-time of a 96-well plate to < 4 min. In addition, imaging cytometry facilitated the rapid collection and long-term storage of test images and data for further evaluation or client consultation. For PEDV and other pathogens, imaging cytometry could provide distinct advantages over classic virus neutralization or FFN assays for the detection and quantitation of neutralizing antibody.

scholarly journals Prevalence of Bovine Viral Diarrhea Virus Genotypes and Antibody against those Viral Genotypes in Fetal Bovine Serum

1998 ◽  
Vol 10 (2) ◽  
pp. 135-139 ◽  
Author(s):  
Steven R. Bolin ◽  
Julia F. Ridpath
Keyword(s):  
Bovine Serum ◽  
Fetal Bovine Serum ◽  
Neutralizing Antibody ◽  
Bovine Viral Diarrhea ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Fetal Bovine ◽  
Viral Diarrhea Virus

One thousand lots of pooled fetal bovine serum (FBS) were tested for contamination with bovine viral diarrhea virus (BVDV) and/or for contamination with neutralizing antibody against BVDV. Noncytopathic or cytopathic BVDV was isolated from 203 lots of FBS. Analysis of the viral isolates identified 115 type 1 and 65 type 2 BVDV isolates. An additional 23 virus isolates were mixtures of >2 BVDV isolates and were not classified to viral genotype. Further characterization of the type 1 viruses identified 51 subgenotype 1a and 64 subgenotype 1b BVDV isolates. Viral neutralizing antibody was detected in 113 lots of FBS. Differential viral neutralization indicated that type 1 BVDV induced the antibody detected in 48 lots of FBS and type 2 BVDV induced the antibody detected in 16 lots of FBS.

scholarly journals Modeling and Forecasting of COVID-19 Spreading by Delayed Stochastic Differential Equations

Axioms ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 18
Author(s):  
Marouane Mahrouf ◽  
Adnane Boukhouima ◽  
Houssine Zine ◽  
El Mehdi Lotfi ◽  
Delfim F. M. Torres ◽  
...  
Keyword(s):  
Real Data ◽  
Economic Damage ◽  
Population Parameter ◽  
The Novel ◽  
First Case ◽  
Epidemiological Trend ◽  
Modeling And Forecasting ◽  
Novel Coronavirus ◽  
Parameter Values ◽  
Stochastic Time

The novel coronavirus disease (COVID-19) pneumonia has posed a great threat to the world recent months by causing many deaths and enormous economic damage worldwide. The first case of COVID-19 in Morocco was reported on 2 March 2020, and the number of reported cases has increased day by day. In this work, we extend the well-known SIR compartmental model to deterministic and stochastic time-delayed models in order to predict the epidemiological trend of COVID-19 in Morocco and to assess the potential role of multiple preventive measures and strategies imposed by Moroccan authorities. The main features of the work include the well-posedness of the models and conditions under which the COVID-19 may become extinct or persist in the population. Parameter values have been estimated from real data and numerical simulations are presented for forecasting the COVID-19 spreading as well as verification of theoretical results.

scholarly journals Reduced sphingosine kinase 1 activity in dengue virus type-2 infected cells can be mediated by the 3′ untranslated region of dengue virus type-2 RNA

2013 ◽  
Vol 94 (11) ◽  
pp. 2437-2448 ◽  
Author(s):  
J. M. Carr ◽  
T. Kua ◽  
J. N. Clarke ◽  
J. K Calvert ◽  
J. R. Zebol ◽  
...  
Keyword(s):  
Cell Death ◽  
Dengue Virus ◽  
Virus Type ◽  
Elongation Factor ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Diarrhea Virus ◽  
Infected Cells ◽  
Dengue Virus Type 2

Sphingosine kinase 1 (SphK1) is a lipid kinase with important roles including regulation of cell survival. We have previously shown reduced SphK1 activity in cells with an established dengue virus type-2 (DENV-2) infection. In this study, we examined the effect of alterations in SphK1 activity on DENV-2 replication and cell death and determined the mechanisms of the reduction in SphK1 activity. Chemical inhibition or overexpression of SphK1 after established DENV-2 infection had no effect on infectious DENV-2 production, although inhibition of SphK1 resulted in enhanced DENV-2-induced cell death. Reduced SphK1 activity was observed in multiple cell types, regardless of the ability of DENV-2 infection to be cytopathic, and was mediated by a post-translational mechanism. Unlike bovine viral diarrhea virus, where SphK1 activity is decreased by the NS3 protein, SphK1 activity was not affected by DENV-2 NS3 but, instead, was reduced by expression of the terminal 396 bases of the 3′ UTR of DENV-2 RNA. We have previously shown that eukaryotic elongation factor 1A (eEF1A) is a direct activator of SphK1 and here DENV-2 RNA co-localized and co-precipitated with eEF1A from infected cells. We propose that the reduction in SphK1 activity late in DENV-2-infected cells is a consequence of DENV-2 out-competing SphK1 for eEF1A binding and hijacking cellular eEF1A for its own replication strategy, rather than a specific host or virus-induced change in SphK1 to modulate viral replication. Nonetheless, reduced SphK1 activity may have important consequences for survival or death of the infected cell.

scholarly journals A Potential Novel COVID-19 Vaccine With RBD-HR1/HR2 Hexamer Structure

2021 ◽  
Author(s):  
Hongbo Liu ◽  
Xiang Gao ◽  
Guoyong Wang ◽  
Jianjun Zhang ◽  
Jiajie Zhou ◽  
...  
Keyword(s):  
Public Health ◽  
Recombinant Protein ◽  
Global Economy ◽  
Neutralizing Antibody ◽  
Scaling Up ◽  
Heptad Repeat ◽  
The Novel ◽  
Health Consequence ◽  
The World ◽  
Frequent Mutations

The COVID-19 pandemic and the continued spreading of the SARS-CoV-2 variants have brought a grave public health consequence and severely devastated the global economy with recessions. Vaccination is considered as one of the most promising and efficient methods to end the COVID-19 pandemic and mitigate the disease conditions if infected. Although a few vaccines have been developed with an unprecedented speed, scientists around the world are continuing pursuing the best possible vaccines with innovations. Comparing to the expensive mRNA vaccines and attenuated/inactivated SARS-CoV-2 vaccines, recombinant protein vaccines have certain advantages, including their safety (non-virus components), potential stronger immunogenicity, broader protection, ease of scaling-up production, reduced cost, etc. In this study, we reported a novel COVID-19 vaccine generated with RBD-HR1/HR2 hexamer that was creatively fused with the RBD domain and heptad repeat 1 (HR1) or heptad repeat 2 (HR2) to form a dumbbell-shaped hexamer to target the spike S1 subunit. The novel hexamer COVID-19 vaccine induced high titers of neutralizing antibody in mouse studies (>100,000), and further experiments also showed that the vaccine also induced an alternative antibody to the HR1 region, which probably alleviated the drop of immunogenicity from the frequent mutations of SARS-CoV-2.

scholarly journals Immunogenicity of Recombinant-Deficient Lactobacillus casei with Complementary Plasmid Expressing Alanine Racemase Gene and Core Neutralizing Epitope Antigen against Porcine Epidemic Diarrhea Virus

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1084
Author(s):  
Fengsai Li ◽  
Xiaona Wang ◽  
Xiaolong Fan ◽  
Ling Sui ◽  
Hailin Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Porcine Epidemic Diarrhea Virus ◽  
Lactobacillus Casei ◽  
Oral Vaccine ◽  
Mucosal Vaccine ◽  
Alanine Racemase ◽  
Main Function ◽  
Neutralizing Epitope ◽  
Diarrhea Virus ◽  
Porcine Epidemic Diarrhea

Porcine epidemic diarrhea (PED), which is caused by the porcine epidemic diarrhea virus (PEDV), has occurred worldwide and poses a serious threat to the pig industry. Intestine is the main function site of PEDV; therefore, it is important to develop an oral mucosal immunity vaccine against this virus infection. Most traditional plasmid delivery vectors use antibiotic genes as a selective marker, easily leading to antibiotic accumulation and gene contamination. In this study, to explore whether the alanine racemase gene (Alr) could be used as a screening marker and develop an efficient oral vaccine against PEDV infection, a recombinant strain was constructed using Lactobacillus casei with Alr deletion (L. casei ΔAlr W56) to deliver the Alr gene and a core-neutralizing epitope (COE) antigen. This recombinant bacterium efficiently induced secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in mice. Compared to the other strains, the recombinant bacteria were able to grow without the addition of D-alanine, revealing that Alr in the plasmid could function normally in defective bacteria. This oral mucosal vaccine would provide a useful strategy to substitute the application of antibiotics in the future and induce efficient immune responses against PEDV infection.

scholarly journals Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/macEnvelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Benjamin von Bredow ◽  
Raiees Andrabi ◽  
Michael Grunst ◽  
Andres G. Grandea ◽  
Khoa Le ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Specific Antibody ◽  
Neutralizing Antibody ◽  
Glycosylation Site ◽  
Antibody Binding ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Broadly Neutralizing Antibody ◽  
Infected Cells ◽  
Hiv 1

ABSTRACTAs a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/maclineage express phylogenetically and antigenically distinct envelope glycoproteins. Thus, HIV-1 Env-specific antibodies do not typically cross-react with the Env proteins of SIVsmm/macisolates. Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/macinfectivity. Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env modulate sensitivity to this antibody. Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization. These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers. To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/macEnv and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCEHere we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity. This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/macEnv and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.

scholarly journals Vaccines and Broadly Neutralizing Antibodies for HIV-1 Prevention

2020 ◽  
Vol 38 (1) ◽  
pp. 673-703 ◽  
Author(s):  
Kathryn E. Stephenson ◽  
Kshitij Wagh ◽  
Bette Korber ◽  
Dan H. Barouch
Keyword(s):  
Clinical Trials ◽  
Neutralizing Antibodies ◽  
Passive Immunization ◽  
Neutralizing Antibody ◽  
Broadly Neutralizing Antibodies ◽  
Aids Pandemic ◽  
Broadly Neutralizing Antibody ◽  
Early Phase Clinical Trials ◽  
Hiv 1 ◽  
Review Current

Development of improved approaches for HIV-1 prevention will likely be required for a durable end to the global AIDS pandemic. Recent advances in preclinical studies and early phase clinical trials offer renewed promise for immunologic strategies for blocking acquisition of HIV-1 infection. Clinical trials are currently underway to evaluate the efficacy of two vaccine candidates and a broadly neutralizing antibody (bNAb) to prevent HIV-1 infection in humans. However, the vast diversity of HIV-1 is a major challenge for both active and passive immunization. Here we review current immunologic strategies for HIV-1 prevention, with a focus on current and next-generation vaccines and bNAbs.

scholarly journals The Roles of Apoptosis in Swine Response to Viral Infection and Pathogenesis of Swine Enteropathogenic Coronaviruses

2020 ◽  
Vol 7 ◽  
Author(s):  
Zhichao Xu ◽  
Yun Zhang ◽  
Yongchang Cao
Keyword(s):  
Viral Infections ◽  
System Development ◽  
Biological Evolution ◽  
Host Responses ◽  
Economic Losses ◽  
Transmissible Gastroenteritis Virus ◽  
Swine Industry ◽  
Animal Virus ◽  
Diarrhea Virus ◽  
Severe Diarrhea

Apoptosis is a tightly regulated mechanism of cell death that plays important roles in various biological processes including biological evolution, multiple system development, anticancer, and viral infections. Swine enteropathogenic coronaviruses invade and damage villous epithelial cells of the small intestine causing severe diarrhea with high mortality rate in suckling piglets. Transmissible gastroenteritis virus (TGEV), Porcine epidemic diarrhea virus (PEDV), Porcine deltacoronavirus (PDCoV), and Swine acute diarrhea syndrome coronavirus (SADS-CoV) are on the top list of commonly-seen swine coronaviruses with a feature of diarrhea, resulting in significant economic losses to the swine industry worldwide. Apoptosis has been shown to be involved in the pathogenesis process of animal virus infectious diseases. Understanding the roles of apoptosis in host responses against swine enteropathogenic coronaviruses infection contribute to disease prevention and control. Here we summarize the recent findings that focus on the apoptosis during swine coronaviruses infection, in particular, TGEV, PEDV, PDCoV, and SADS-CoV.

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