scholarly journals Application of Heparin Affinity Chromatography to Produce a Differential Vaccine without Eliciting Antibodies against the Nonstructural Proteins of the Serotype O Foot-and-Mouth Disease Viruses

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1405
Author(s):  
Sun Young Park ◽  
Jung-Min Lee ◽  
Ah-Young Kim ◽  
Sang Hyun Park ◽  
Jae-Seok Kim ◽  
...  
Keyword(s):  
Affinity Chromatography ◽  
Neutralizing Antibodies ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Vaccine Antigen ◽  
Nonstructural Proteins ◽  
Serotype O ◽  
Intact Virus ◽  
Foot And Mouth ◽  
Heparin Affinity

Although polyethylene glycol (PEG) application is the most widely used method in removing nonstructural proteins (NSPs) for foot-and-mouth disease (FMD) vaccine production, some NSPs remaining in the antigen could elicit antibodies against these proteins after repeated vaccinations in livestock. Therefore, the purpose of this study was to purify the FMD virus (FMDV) via affinity chromatography using a heparin ligand to remove most proteins, including NSPs. Chromatography showed an intact virus (146S) particle recovery of 70% or more for three different strains of serotype O FMDV (two locally isolated strains and one genetically modified strain). The experimental vaccine made with antigens eluted via heparin affinity chromatography elicited virus-neutralizing antibodies against homologous viruses but did not induce antibodies against NSPs even after five immunizations in goats; this indicated that the NSPs were effectively removed from the vaccine antigen. This method can then be used to produce a higher-quality vaccine compared with PEG application in terms of the purity of the FMD vaccine. Therefore, this result would be an important groundwork for advanced FMD vaccine manufacturing in the near future.

scholarly journals Structures of Foot-and-mouth Disease Virus with neutralizing antibodies derived from recovered natural host reveal a mechanism for cross-serotype neutralization

2021 ◽  
Vol 17 (4) ◽  
pp. e1009507
Author(s):  
Yong He ◽  
Kun Li ◽  
Yimei Cao ◽  
Zixian Sun ◽  
Pinghua Li ◽  
...  
Keyword(s):  
Disease Virus ◽  
Neutralizing Antibodies ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Universal Vaccine ◽  
Isolation Technique ◽  
Serotype O ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Natural Hosts

The development of a universal vaccine against foot-and-mouth disease virus (FMDV) is hindered by cross-serotype antigenic diversity and by a lack of knowledge regarding neutralization of the virus in natural hosts. In this study, we isolated serotype O-specific neutralizing antibodies (NAbs) (F145 and B77) from recovered natural bovine hosts by using the single B cell antibody isolation technique. We also identified a serotype O/A cross-reacting NAb (R50) and determined virus-NAb complex structures by cryo-electron microscopy at near-atomic resolution. F145 and B77 were shown to engage the capsid of FMDV-O near the icosahedral threefold axis, binding to the BC/HI-loop of VP2. In contrast, R50 engages the capsids of both FMDV-O and FMDV-A between the 2- and 5-fold axes and binds to the BC/EF/GH-loop of VP1 and to the GH-loop of VP3 from two adjacent protomers, revealing a previously unknown antigenic site. The cross-serotype neutralizing epitope recognized by R50 is highly conserved among serotype O/A. These findings help to elucidate FMDV neutralization by natural hosts and provide epitope information for the development of a universal vaccine for cross-serotype protection against FMDV.

Two Cross-Protective Antigen Sites on Foot-and-Mouth Disease Virus Serotype O Structurally Revealed by Broadly Neutralizing Antibodies from Cattle

2021 ◽  
Vol 95 (21) ◽  
Author(s):  
Kun Li ◽  
Yong He ◽  
Li Wang ◽  
Pinghua Li ◽  
Sheng Wang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Antigen ◽  
Foot And Mouth Disease ◽  
Neutralizing Antibody ◽  
Mouth Disease ◽  
Antigenic Structure ◽  
Serotype O ◽  
Mouth Disease Virus ◽  
Virus Serotype ◽  
Foot And Mouth

FMDV is the causative agent of foot-and-mouth disease (FMD), which is one of the most contagious and economically devastating diseases of domestic animals. The antigenic structure of FMDV serotype O is rather complicated, especially for those sites that can elicit a cross-protective neutralizing antibody response.

scholarly journals Implication of Broadly Neutralizing Bovine Monoclonal Antibodies in the Development of an Enzyme-Linked Immunosorbent Assay for Detecting Neutralizing Antibodies against Foot-and-Mouth Disease Virus Serotype O

2019 ◽  
Vol 57 (12) ◽  
Author(s):  
Yimei Cao ◽  
Kun Li ◽  
Sheng Wang ◽  
Yuanfang Fu ◽  
Pu Sun ◽  
...  
Keyword(s):  
Disease Virus ◽  
Neutralizing Antibodies ◽  
Foot And Mouth Disease ◽  
Neutralizing Antibody ◽  
Mouth Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serotype O ◽  
Fmdv Serotype ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT Vaccination with inactivated vaccines is still the main measure to control foot-and-mouth disease (FMD) in areas where the disease is endemic, and the level of neutralizing antibody in vaccinated animals is directly related to their protection against virus challenge. Currently, neutralizing antibody is mainly detected using the virus neutralization test (VNT) based on cell culture, which is laborious and time-consuming and requires restrictive biocontainment facilities. In this study, two broadly neutralizing antibodies (bnAbs), E46 and F128, were successfully produced using techniques for the isolation of single B cells from peripheral blood mononuclear cells (PBMCs) from bovines sequentially immunized with three topotypes of foot-and-mouth disease virus (FMDV) serotype O. Based on these bnAbs, a blocking enzyme-linked immunosorbent assay (ELISA) for detecting neutralizing antibodies (NA-ELISA) against FMDV serotype O was developed. The specificity and sensitivity of the test were estimated to be 99.21% and 100%, respectively. A significant correlation (P < 0.01) was observed between the NA-ELISA titers and the VNT titers for all sera from vaccinated animals and for all tested strains, suggesting that the NA-ELISA could detect neutralizing antibodies against FMDV serotype O strains of wide antigenic and molecular diversity and could be used for the evaluation of protective immunity.

scholarly journals Selection of Vaccine Candidate for Foot-and-Mouth Disease Virus Serotype O Using a Blocking Enzyme-Linked Immunosorbent Assay

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 387
Author(s):  
Yimei Cao ◽  
Kun Li ◽  
Xiangchuan Xing ◽  
Huifang Bao ◽  
Nana Huang ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Strain Selection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serotype O ◽  
Foot And Mouth ◽  
Selection Of

Foot-and-mouth disease (FMD) is a highly contagious disease and one of the most economically important diseases of livestock. Vaccination is an important measure to control FMD and selection of appropriate vaccine strains is crucial. The objective of this study was to select a vaccine candidate and to evaluate the potential of a blocking ELISA for detecting neutralizing antibodies (NA-ELISA) in vaccine strain selection. Binary ethylenimine inactivated vaccines, prepared from four representative circulating strains (FMDV O/Mya/98, SCGH/CHA/2016, O/Tibet/99, and O/XJ/CHA/2017) belonging to four lineages within three different topotypes of FMD virus (FMDV) serotype O in China, were used to vaccinate cattle (12–13 animals for each strain), sheep (12–13 animals for each strain), and pigs (10 animals for each strain). The results of immunogenicity comparison showed that O/XJ/CHA/2017 exhibited the highest immunogenicity among the four strains in pigs, cattle, and sheep both by NA-ELISA and virus neutralizing test (VNT). Cross-neutralization analysis indicated that O/XJ/CHA/2017 displayed broad antigen spectrum and was antigenically matched with other three representative strains both by NA-ELISA and VNT. In addition, A significant correlation (p < 0.0001) was observed between the NA-ELISA titers and the VNT titers for four representative strains. The results showed that O/XJ/CHA/2017 was a promising vaccine strain candidate and NA-ELISA was comparable to VNT in neutralizing antibodies detection and could be used as the reference test system for vaccine strain selection.

Antiviral potential of ivermectin against foot-and-mouth disease virus, serotype O, A and Asia-1

2021 ◽  
pp. 104914
Author(s):  
Zahra Naeem ◽  
Sohail Raza ◽  
Saba Afzal ◽  
Ali Ahmad Sheikh ◽  
Muhammad Muddassir Ali ◽  
...  
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Serotype O ◽  
Mouth Disease Virus ◽  
Virus Serotype ◽  
Foot And Mouth

scholarly journals Advances in Antigenic Peptide-Based Vaccine and Neutralizing Antibodies against Viruses Causing Hand, Foot, and Mouth Disease

2019 ◽  
Vol 20 (6) ◽  
pp. 1256 ◽  
Author(s):  
Mohd Anasir ◽  
Chit Poh
Keyword(s):  
Neutralizing Antibodies ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Antigenic Peptide ◽  
Effective Vaccine ◽  
Inactivated Vaccine ◽  
Antigenic Peptides ◽  
Foot And Mouth ◽  
Etiological Agents

Hand, foot, and mouth disease (HFMD) commonly produces herpangina, but fatal neurological complications have been observed in children. Enterovirus 71 (EV-A71) and Coxsackievirus 16 (CV-A16) are the predominant viruses causing HFMD worldwide. With rising concern about HFMD outbreaks, there is a need for an effective vaccine against EV-A71 and CV-A16. Although an inactivated vaccine has been developed against EV-A71 in China, the inability of the inactivated vaccine to confer protection against CV-A16 infection and other HFMD etiological agents, such as CV-A6 and CV-A10, necessitates the exploration of other vaccine platforms. Thus, the antigenic peptide-based vaccines are promising platforms to develop safe and efficacious multivalent vaccines, while the monoclonal antibodies are viable therapeutic and prophylactic agents against HFMD etiological agents. This article reviews the available information related to the antigenic peptides of the etiological agents of HFMD and their neutralizing antibodies that can provide a basis for the design of future therapies against HFMD etiological agents.

scholarly journals Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus

2014 ◽  
Vol 95 (5) ◽  
pp. 1104-1116 ◽  
Author(s):  
Amin S. Asfor ◽  
Sasmita Upadhyaya ◽  
Nick J. Knowles ◽  
Donald P. King ◽  
David J. Paton ◽  
...  
Keyword(s):  
Amino Acid ◽  
Guinea Pig ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Amino Acid Residues ◽  
Serotype O ◽  
Antigenic Sites ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
The Impact

Five neutralizing antigenic sites have been described for serotype O foot-and-mouth disease viruses (FMDV) based on monoclonal antibody (mAb) escape mutant studies. However, a mutant virus selected to escape neutralization of mAb binding at all five sites was previously shown to confer complete cross-protection with the parental virus in guinea pig challenge studies, suggesting that amino acid residues outside the mAb binding sites contribute to antibody-mediated in vivo neutralization of FMDV. Comparison of the ability of bovine antisera to neutralize a panel of serotype O FMDV identified three novel putative sites at VP2-74, VP2-191 and VP3-85, where amino acid substitutions correlated with changes in sero-reactivity. The impact of these positions was tested using site-directed mutagenesis to effect substitutions at critical amino acid residues within an infectious copy of FMDV O1 Kaufbeuren (O1K). Recovered viruses containing additional mutations at VP2-74 and VP2-191 exhibited greater resistance to neutralization with both O1K guinea pig and O BFS bovine antisera than a virus that was engineered to include only mutations at the five known antigenic sites. The changes at VP2-74 and VP3-85 are adjacent to critical amino acids that define antigenic sites 2 and 4, respectively. However VP2-191 (17 Å away from VP2-72), located at the threefold axis and more distant from previously identified antigenic sites, exhibited the most profound effect. These findings extend our knowledge of the surface features of the FMDV capsid known to elicit neutralizing antibodies, and will improve our strategies for vaccine strain selection and rational vaccine design.

scholarly journals Selection of vaccine strains for serotype O foot-and-mouth disease viruses (2007–2012) circulating in Southeast Asia, East Asia and Far East

Vaccine ◽  
2017 ◽  
Vol 35 (51) ◽  
pp. 7147-7153 ◽  
Author(s):  
Mana Mahapatra ◽  
Sasmita Upadhyaya ◽  
Sharie Aviso ◽  
Aravindh Babu ◽  
Geoff Hutchings ◽  
...  
Keyword(s):  
Southeast Asia ◽  
East Asia ◽  
Far East ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Serotype O ◽  
Foot And Mouth ◽  
Selection Of

scholarly journals Structural and molecular basis for foot-and-mouth disease virus neutralization by two potent protective antibodies

2021 ◽  
Author(s):  
Hu Dong ◽  
Pan Liu ◽  
Manyuan Bai ◽  
Kang Wang ◽  
Rui Feng ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Foot And Mouth Disease ◽  
Therapeutic Benefit ◽  
Mouth Disease ◽  
Economic Losses ◽  
Viral Particles ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Protective Antibodies

Outbreaks of Foot-and-mouth disease (FMD) caused by FMD virus result in significant economic losses. Vaccination is helpful, but the benefits are diminished with antigenic diversity within serotypes, instability of the immunogen and inability to confer protection for long durations. Here we have further dissected the mechanisms underpinning the protective efficacy of two previously reported neutralizing antibodies (NAbs), M8 and M170. The atomic details of the epitopes of M8 and M170 unveiled suggest that protection is conferred by disrupting the virus-receptor interactions. Consequently, administration of these NAbs conferred prophylactic and therapeutic benefit in guinea pigs, raising the possibility of administering NAbs before or during vaccination to confer immediate protection; well before the bolstering of the immune response by the vaccine. Differences in the residues and the conformation of elements making up the epitopes explain the differences in specificities of M8 and M170. An ability to bind 146S viral particles specifically, but not 12S degraded components, highlights a likely role for M170 in the quality control of vaccines.

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