Foot-and-mouth disease or hoof-and-mouth disease (Aphtae epizooticae) is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, including domestic and wild bovids. The virus causes a high fever for two or three days, followed by blisters inside the mouth and on the feet that may rupture and cause lameness. Foot-and-mouth disease is a severe plague for animal farming, since it is highly infectious and can be spread by infected animals through aerosols, through contact with contaminated farming equipment, vehicles, clothing or feed, and by domestic and wild predators. Its containment demands considerable efforts in vaccination, strict monitoring, trade restrictions and quarantines, and occasionally the elimination of millions of animals. Susceptible animals include cattle, water buffalo, sheep, goats, pigs, antelope, deer, and bison. It has also been known to infect hedgehogs and elephants, and llama and alpaca may develop mild symptoms, but are resistant to the disease and do not pass it on to others of the same species. In laboratory experiments, mice and rats and chickens have been successfully infected by artificial means, but it is not believed that they would contract the disease under natural conditions.Humans are very rarely affected. The virus responsible for the disease is a picornavirus, the prototypic member of the genus Aphthovirus. Infection occurs when the virus particle is taken into a cell of the host. The cell is then forced to manufacture thousands of copies of the virus, and eventually bursts, releasing the new particles in the blood. The virus is highly variable,which limits the effectiveness of vaccination (Wiki: Foot and mouth disease).
II. Vaccine Related Pathogen Genes
1. 1D
Gene Name :
1D
Sequence Strain (Species/Organism) :
Foot-and-mouth disease virus - type Asia 1
Protein Note :
Picornavirus capsid protein domain_like. Picornaviruses are non-enveloped plus-strand ssRNA animal viruses with icosahedral capsids composed of 60 copies each of 4 virus encoded proteins; alignment includes picornaviridae, like poliovirus, hepatitis A...; cl13999
>ABR13034.1 1D protein, partial [Foot-and-mouth disease virus - type Asia 1]
TTTTGESADPVTTTVENYGGETQTARRLHTDVAFVLDRFVKLTAPKNIQTLDLMQIPSHTLVGALLRSAT
YYFSDLEVAIVHTGPITWVPNGSPKDALDNQTNPTAYQKQPVTRLALPYTAPHRVLATVYNGKTTYGETT
ARRGDMAALAQRLSGRLPTSFNYGAVKAETITELLFRMKRAETYCPRPLLALDTTQDRRKQEIIAPEKQM
M
Protein Note :
Picornavirus capsid protein domain_like. Picornaviruses are non-enveloped plus-strand ssRNA animal viruses with icosahedral capsids composed of 60 copies each of 4 virus encoded proteins; alignment includes picornaviridae, like poliovirus, hepatitis A...; cl13999
Vaccination Protocol:
Thirty-two cattle of 6–7 months of age were housed separately in six groups of five (vaccinated animals) and one group of two (un-vaccinated controls) within the isolation units at the Institute for Animal Health, Pirbright. The six groups of vaccinates were immunised as follows: Group 1 with 2 mg PLG-pcDNA3.1/P12A3C3D + 0.4 mg pcDNA3.1/bGM-CSF (DNA + PLG + GMCSF), Group 2 with 2 mg PLG-pcDNA3.1/P12A3C3D + 0.4 mg pcDNA3.1/bGM-CSF + electroporation (DNA + PLG + GMCSF + elec), Group 3 with 2 mg pcDNA3.1/P12A3C3D + 0.4 mg pcDNA3.1/bGM-CSF (DNA + GMCSF), Group 4 with 2 mg pcDNA3.1/P12A3C3D + 0.4 mg pcDNA3.1/bGM-CSF + electroporation (DNA + GMCSF + elec), Group 5 with 2 mg pcDNA3.1/P12A3C3D + electroporation (DNA + elec), and Group 6 with conventional vaccine (Fowler et al., 2012).
Vaccine Immune Response Type:
VO_0003057
Immune Response:
All DNA vaccinated cattle generated a detectable neutralising antibody response at 21 days post 1st vaccination (Fowler et al., 2012).
Challenge Protocol:
On day 133 post primary vaccination, four cattle in each of vaccination groups 3–6 only were randomly selected, together with two un-vaccinated controls and intradermolingually challenged in two sites with 105 TCID50, 0.1 ml per site, of cattle adapted O1 Lausanne FMDV (Fowler et al., 2012).
Efficacy:
Conventionally vaccinated cattle were fully protected from experimental challenge, as determined by absence of generalised disease (Table 2). In addition 6 of the 8 DNA vaccinated cattle in groups 4 and 5 (DNA + GMCSF + elec and DNA + elec) were fully protected despite these DNA vaccinated animals being challenged 91 days after the protein boost (Fowler et al., 2012).
2. Foot and mouth disease DNA vaccine pWRMHX encoding a minimal self-cleaving ribozyme
Efficacy:
Swine inoculated with pWRMHX did not show any signs of disease and produced neutralizing antibodies to FMDV, and 20% of the vaccinated animals were protected from FMDV challenge (Ward et al., 1997).
3. Foot-and-Mouth Disease Virus Cationic Microparticle-coated DNA Vaccine
Vaccination Protocol:
Sixty male guinea pigs of 10 weeks of age were divided in to three groups each containing 20 animals. Group I was inoculated with a 10 µg of pVAC- 1D (naked DNA vaccinated group), group II was inoculated with pVAC-1D coated on PLG microparticles (pVAC-1D + PLG group) and group III received PBS. All the animals were inoculated intramuscularly in the gluteal region of the right leg (Reddy et al., 2012).
Vaccine Immune Response Type:
VO_0003057
Immune Response:
Immunization with pVAC 1D-PLG elicited significantly enhanced neutralization antibody responses compared to naked DNA vaccine (Reddy et al., 2012).
Efficacy:
Microparticles coated plasmid DNA-injected guinea pigs were protected when challenged with FMD virus (Reddy et al., 2012).
4. Foot-and-Mouth Disease Virus DNA Vaccine pSinCMV-Vac-MEG990
Vaccination Protocol:
Immunization of guinea pigs with the construct at dose rate of 10, 5, 2 and 1 μg per animal was through an intramuscular route (Dar et al., 2012).
Vaccine Immune Response Type:
VO_0003057
Immune Response:
Immune responses included significant neutralizing antibody induction at all doses against all serotypes tested as compared to non-immunized controls, and delayed appearance and reduced severity of FMD lesions (Dar et al., 2012).
Challenge Protocol:
Viral challenge of guinea pigs was 4 week post-immunization with 1000 GPID(50) of FMDV serotype A (Dar et al., 2012).
Efficacy:
Two of six and one of six guinea pigs were completely protected in 10 and 5 μg immunized groups (Dar et al., 2012).
cDNA clone for FMDV serotype A Indian vaccine strain lacking 58 amino acid residues (87-144 amino acid position) in the carboxy-terminal region of the viral 3A protein. (Dhanesh et al., 2020)
e. Preparation
The rFMDVΔ3A^87-144 viruses were grown in BHK-21 monolayer in roller bottles and harvested after observing complete CPE. The virus supernatant was inactivated with 3 mM BEI for 24 h at room temperature after chloroform clarification. Three back passaging of the inactivated virus in BHK-21 were carried out to ensure the absence of residual infectivity. The inactivated virus was concentrated with PEG as described earlier and purified by cesium chloride density gradient ultracentrifugation to estimate the antigen content in the concentrated suspension by spectrophotometer. The vaccines were formulated by blending the PEG concentrated antigen and MontanideISA-201 VG adjuvant (Seppic, France) by homogenization to have 1.2 μg antigen per dose in 250 μl vaccine. (Dhanesh et al., 2020)
f. Immunization Route
Intradermal injection (i.d.)
g. Description
rFMDVΔ3A^87-144 vaccine induces potent immune response with 100% protective efficacy upon challenge with homologous virus in guinea pigs. (Dhanesh et al., 2020)
h.
Guinea pig Response
Vaccination Protocol:
Thirty-six healthy male guinea pigs of 3 months age were randomly divided into three groups of 12 each. The first group received 1.2 μg of FMDV^WT virus antigen, and the second group received a similar dose of rFMDVΔ3A^87-144 virus antigen. The third group received phosphate-buffered saline to serve as the control. All the three groups received a similar dose of booster injections of respective antigen post 28 days of primary immunization. (Dhanesh et al., 2020)
Immune Response:
The FMDV^WT and rFMDVΔ3A^87-144 vaccinated group developed a mean serum titer of 1.38 log10SN50 and 1.35 log10SN50, respectively, on 28 dpv. Further, the serum titer of both the groups increased to 1.87 log10SN50 and 1.70 log10SN50, respectively, by 28 dpb, indicating a potent anamnestic immune response on second exposure with the antigen. Both conventional and the deletion mutant virus vaccine produced a similar immune response with no significant difference (p > 0.05). (Dhanesh et al., 2020)
Challenge Protocol:
After 28 days post-booster, all the groups were challenged with 100 GPID50 of guinea pig adapted FMDV^WT in 50-μl volume by intradermal tracking in the left rear footpad. (Dhanesh et al., 2020)
Efficacy:
100% protection was conferred by both vaccines as no systemic infection was noticed in any of the vaccinated animals. (Dhanesh et al., 2020)
V. References
1. Joyappa et al., 2009: Joyappa DH, Kumar CA, Banumathi N, Reddy GR, Suryanarayana VV. Calcium phosphate nanoparticle prepared with foot and mouth disease virus P1-3CD gene construct protects mice and guinea pigs against the challenge virus. Veterinary microbiology. 2009; 139(1-2); 58-66. [PubMed: 19505774].
2. Shao et al., 2005: Shao HJ, Chen L, Su YB. DNA fragment encoding human IL-1beta 163-171 peptide enhances the immune responses elicited in mice by DNA vaccine against foot-and-mouth disease. Veterinary research communications. 2005; 29(1); 35-46. [PubMed: 15727290].
3. Wang et al., 2006: Wang F, He XW, Jiang L, Ren D, He Y, Li DA, Sun SH. Enhanced immunogenicity of microencapsulated multiepitope DNA vaccine encoding T and B cell epitopes of foot-and-mouth disease virus in mice. Vaccine. 2006; 24(12); 2017-2026. [PubMed: 16414158].
4. Ward et al., 1997: Ward G, Rieder E, Mason PW. Plasmid DNA encoding replicating foot-and-mouth disease virus genomes induces antiviral immune responses in swine. Journal of virology. 1997; 71(10); 7442-7447. [PubMed: 9311823].
