Genetic stability of foot-and-mouth disease virus during long-term infections in 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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Structures of Foot-and-mouth Disease Virus with neutralizing antibodies derived from recovered natural host reveal a mechanism for cross-serotype neutralization

PLoS Pathogens ◽

10.1371/journal.ppat.1009507 ◽

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.

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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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Long-term Observations on the Antibody Responses of Cattle Vaccinated with Modified Strains of Foot-and-mouth Disease Virus

Research in Veterinary Science ◽

10.1016/s0034-5288(18)34758-1 ◽

1965 ◽

Vol 6 (2) ◽

pp. 220-229

Author(s):

W.A. Geering ◽

SallyP. Carter ◽

K.A.J. Herniman

Keyword(s):

Disease Virus ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Antibody Responses ◽

Mouth Disease Virus ◽

Foot And Mouth

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SAT2 Foot-and-Mouth Disease Virus Structurally Modified for Increased Thermostability

Journal of Virology ◽

10.1128/jvi.02312-16 ◽

2017 ◽

Vol 91 (10) ◽

Cited By ~ 11

Author(s):

Katherine A. Scott ◽

Abhay Kotecha ◽

Julian Seago ◽

Jingshan Ren ◽

Elizabeth E. Fry ◽

...

Keyword(s):

Disease Virus ◽

Genetic Stability ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Ph Stability ◽

Cold Chain ◽

Wild Type Virus ◽

Mouth Disease Virus ◽

Foot And Mouth ◽

The Stability

ABSTRACT Foot-and-mouth disease virus (FMDV), particularly strains of the O and SAT serotypes, is notoriously unstable. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of immunity with a poor duration and hence require more frequent vaccinations to ensure protection. In silico calculations predicted residue substitutions that would increase interactions at the interpentamer interface, supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses in regard to their growth kinetics, antigenicity, plaque morphology, genetic stability, and temperature, ionic, and pH stability by using Thermofluor and inactivation assays in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutant for temperature and pH stability was the S2093Y single mutant, while other promising mutants were the E3198A, L2094V, and S2093H single mutants and the F2062Y-H2087M-H3143V triple mutant. Although the S2093Y mutant had the greatest stability, it exhibited smaller plaques, a reduced growth rate, a change in monoclonal antibody footprint, and poor genetic stability properties compared to those of the wild-type virus. However, these factors affecting production can be overcome. The addition of 1 M NaCl was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilizing SAT2 vaccines. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of some serotypes, such as SAT2, affects the quality of vaccines and therefore the duration of immunity. We have shown that we can improve the stability of SAT2 viruses by mutating residues at the capsid interface through predictive modeling. This is an important finding for the potential use of such mutants in improving the stability of SAT2 vaccines in countries where FMD is endemic, which rely heavily on the maintenance of the cold chain, with potential improvement to the duration of immune responses.

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High resolution surface structure of foot-and-mouth disease virus

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100082741 ◽

1978 ◽

Vol 36 (2) ◽

pp. 376-377

Author(s):

S. S. Breese ◽

H. L. Bachrach

Keyword(s):

Electron Microscopy ◽

High Resolution ◽

Surface Structure ◽

Disease Virus ◽

Potassium Phosphate ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Physical Measurements ◽

Mouth Disease Virus ◽

Foot And Mouth

Models for the structure of foot-and-mouth disease virus (FMDV) have been proposed from chemical and physical measurements (Brown, et al., 1970; Talbot and Brown, 1972; Strohmaier and Adam, 1976) and from rotational image-enhancement electron microscopy (Breese, et al., 1965). In this report we examine the surface structure of FMDV particles by high resolution electron microscopy and compare it with that of particles in which the outermost capsid protein VP3 (ca. 30, 000 daltons) has been split into smaller segments, two of which VP3a and VP3b have molecular weights of about 15, 000 daltons (Bachrach, et al., 1975).Highly purified and concentrated type A12, strain 119 FMDV (5 mg/ml) was prepared as previously described (Bachrach, et al., 1964) and stored at 4°C in 0. 2 M KC1-0. 5 M potassium phosphate buffer at pH 7. 5. For electron microscopy, 1. 0 ml samples of purified virus and trypsin-treated virus were dialyzed at 4°C against 0. 2 M NH4OAC at pH 7. 3, deposited onto carbonized formvar-coated copper screens and stained with phosphotungstic acid, pH 7. 3.

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