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

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.

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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

Journal of Clinical Microbiology ◽

10.1128/jcm.01030-19 ◽

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.

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Protective Immune Response to Foot-and-Mouth Disease Virus with VP1 Expressed in Transgenic Plants

Journal of Virology ◽

10.1128/jvi.72.2.1688-1690.1998 ◽

1998 ◽

Vol 72 (2) ◽

pp. 1688-1690 ◽

Cited By ~ 88

Author(s):

C. Carrillo ◽

A. Wigdorovitz ◽

J. C. Oliveros ◽

P. I. Zamorano ◽

A. M. Sadir ◽

...

Keyword(s):

Disease Virus ◽

Neutralizing Antibodies ◽

Foot And Mouth Disease ◽

Viral Disease ◽

Mouth Disease ◽

Structural Protein ◽

Mouth Disease Virus ◽

Foot And Mouth ◽

Natural Hosts ◽

Genes Encoding

ABSTRACT It has been reported recently that genes encoding antigens of bacterial and viral pathogens can be expressed in plants in a form in which they retain native immunogenic properties. The structural protein VP1 of foot-and-mouth disease virus (FMDV), which has frequently been shown to contain critical epitopes, has been expressed in different vectors and shown to induce virus-neutralizing antibodies and protection in experimental and natural hosts. Here we report the production of transformed plants (Arabidopsis thaliana) expressing VP1. Mice immunized with leaf plant extracts elicited specific antibody responses to synthetic peptides representing amino acid residues 135 to 160 of VP1, to VP1 itself, and to intact FMDV particles. Additionally, all of the immunized mice were protected against challenge with virulent FMDV. To our knowledge, this is the first study showing protection against a viral disease by immunization with an antigen expressed in a transgenic plant.

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

Microbial Pathogenesis ◽

10.1016/j.micpath.2021.104914 ◽

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

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Innate Immune Defenses Induced by CpG Do Not Promote Vaccine-Induced Protection against Foot-and-Mouth Disease Virus in Pigs

Clinical and Vaccine Immunology ◽

10.1128/cvi.00018-09 ◽

2009 ◽

Vol 16 (8) ◽

pp. 1151-1157 ◽

Cited By ~ 25

Author(s):

M. P. Alves ◽

L. Guzylack-Piriou ◽

V. Juillard ◽

J.-C. Audonnet ◽

T. Doel ◽

...

Keyword(s):

Disease Virus ◽

Large Scale ◽

Control Strategies ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Innate Immune ◽

Noticeable Effect ◽

Mouth Disease Virus ◽

Foot And Mouth ◽

Natural Hosts

ABSTRACT Emergency vaccination as part of the control strategies against foot-and-mouth disease virus (FMDV) has the potential to limit virus spread and reduce large-scale culling. To reduce the time between vaccination and the onset of immunity, immunostimulatory CpG was tested for its capacity to promote early protection against FMDV challenge in pigs. To this end, CpG 2142, an efficient inducer of alpha interferon, was injected intramuscularly. Increased transcription of Mx1, OAS, and IRF-7 was identified as a sensitive measurement of CpG-induced innate immunity, with increased levels detectable to at least 4 days after injection of CpG formulated with Emulsigen. Despite this, CpG combined with an FMD vaccine did not promote protection. Pigs vaccinated 2 days before challenge had disease development, which was at least as acute as that of unvaccinated controls. All pigs vaccinated 7 days before challenge were protected without a noticeable effect of CpG. In summary, our results demonstrate the caution required when translating findings from mouse models to natural hosts of FMDV.

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