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Vaccination against foot-and-mouth disease: the implications for Canada.

Vaccination of susceptible animals against foot-and-mouth disease (FMD) is a well established strategy for helping to combat the disease. Traditionally, FMD vaccine has been used to control a disease incursion in countries where the disease has been endemic rather than in countries considered free of the disease. In 2001, the use of vaccine was considered but not implemented in the United Kingdom (1), whereas vaccine was used to help to control FMD in The Netherlands (2,3). Canadian contingency plans provide for the use of vaccine; Canada is a member of the North American Foot-and-Mouth Disease Vaccine Bank, which could supply vaccine if needed. This article explains why Canada might use FMD vaccine to combat an outbreak and the factors that are relevant to the disposal of vaccinated animals and their products. It concludes that vaccination is an important mechanism in Canada's preparedness for an outbreak of FMD and that products from vaccinated animals are safe for human consumption.

Animals↗

Transmission of the virus of foot and mouth disease between animals and man.

The virus of foot and mouth disease causes severe epizootics in animals and infrequently evokes painful, but transient, clinical signs in man. Adults in certain occupational groups and young children are particularly exposed to risk. Infected persons may disseminate virus for up to about 14 days. The virus can be transmitted from animals to animals, from animals to man, from man to animals and, probably, from man to man. Evidence for transfer of the disease between human and animal populations is reviewed in detail and modern methods of diagnosis are described. Predisposing factors play an important role in the development of overt foot and mouth disease in man. Subclinical infection occurs. The possibility of aerial transfer of the virus between man and domestic livestock constitutes a hazard, especially to the latter. Attention is directed to the need for sophisticated diagnostic techniques, to requirements for adequate precautions in the handling and disposal of affected animals, and to hygienic measures for disease control.

Animals↗

A note on outbreaks caused by mixed foot-and-mouth disease virus infections.

Two outbreaks of foot-and-mouth disease (FMD) in vaccinated cattle were investigated wherein a mixed infection due to FMD virus (FMDV) types O and Asia 1 was detected by sandwich enzyme-linked immunosorbent assay (ELISA) and confirmed by antigen capture polymerase chain reaction (PCR). The clinical picture and the epidemiological data on these outbreaks are presented. The isolated virus strains were compared to the respective vaccine strains by means of monoclonal antibody (MAb) profiling and nucleotide sequence analysis. The probable cause of the mixed FMDV infection and its significance in disease control are discussed.

Amino Acid Sequence↗

Binary ethylenimine as an inactivant for foot-and-mouth disease virus and its application for vaccine production.

Foot-and-mouth disease virus was inactivated with binary ethylenimine formed apart from or directly in the virus suspension by the cyclization of 2-bromoethylamine hydrobromide or 2-chloroethylamine hydrochloride under alkaline conditions. The inactivation rates with binary ethylenimine prepared apart from the virus suspension in dilute sodium hydroxide with either 2-bromoethylamine hydrobromide or 2-chlorethylamine hydrochloride were higher than with pure ethylenimine. When binary ethylenime was prepared directly in the virus suspension only 2-bromoethylamine hydrobromide gave acceptable inactivation rates. The reduced inactivation rates for binary ethylenimine directly prepared in the virus suspension are due to the different cyclization rates of 2-bromoethylamine hydrobromide and 2-chloroethylamine hydrochloride and to the interference of bicarbonate in the cyclization reaction. The complement fixing antigen of foot-and-mouth disease virus was not affected by binary ethylenimine inactivation. Vaccines prepared with foot-and-mouth disease virus inactivated by binary ethylenimine were comparable in their immunogenicity to vaccines prepared with ethylenimine or N-acetylethylenimine used as inactivants. Application of binary ethylenimine in the preparation of foot-and-mouth disease vaccines considerably reduces the potential danger associated with handling pure ethylenimine and other aziridines.

Animals↗

Pandemic strain of foot-and-mouth disease virus serotype O.

A particular genetic lineage of foot-and-mouth disease virus (FMDV) serotype O, which we have named the PanAsia strain, was responsible for an explosive pandemic in Asia and extended to parts of Africa and Europe from 1998 to 2001. In 2000 and 2001, this virus strain caused outbreaks in the Republic of Korea, Japan, Russia, Mongolia, South Africa, the United Kingdom, Republic of Ireland, France, and the Netherlands, countries which last experienced FMD outbreaks decades before (ranging from 1934 for Korea to 1984 for the Netherlands). Although the virus has been controlled in all of these normally FMD-free or sporadically infected countries, it appears to be established throughout much of southern Asia, with geographically separated lineages evolving independently. A pandemic such as this is a rare phenomenon but demonstrates the ability of newly emerging FMDV strains to spread rapidly throughout a wide region and invade countries previously free from the disease.

Animals↗

Foot-and-mouth disease. A review for the practitioner.

Foot-and-mouth disease (FMD) is perhaps the most infectious disease known to human and veterinary medicine. This article is written with the practitioner in mind, concentrating on early recognition, epidemiology, occurrence around the world, and sampling and diagnostic methods. The article stresses that there are numerous FMD viruses, and not all behave in a similar fashion. The practitioner must be acute in his or her herd inspection of animals in which vesicular disease is suspected and knowledgeable as to differential diagnosis.

Animals↗

Aspects of the persistence of foot-and-mouth disease virus in animals--the carrier problem.

Foot-and-mouth disease virus (FMDV) is a member of the Aphthovirus genus in the Picornaviridae family. Seven distinct serotypes, each including a wide range of variants, have been defined. FMD, affects wild and domesticated ruminants and pigs, is difficult to control and is the major constraint to international trade in livestock and animal products. After the acute stage of infection, FMDV may cause a prolonged, asymptomatic but persistent infection in ruminants. Also, vaccinated or naturally immune animals subsequently exposed to live virus may become persistently infected (the so-called carriers), a situation which can result in export embargoes if vaccination is included in a country's control policy.

Animals↗

Genetic comparison of large fragment of the 5'untranslated region among foot-and-mouth disease viruses with special reference to serotype Asia1.

Foot-and-mouth disease (FMD), the most economically important disease of cloven-hoofed animals, is endemic in India. Sequence analysis revealed that phylogenetic grouping of type Asia1 field isolates on the basis of the large fragment of the 5'untranslated region (5'LF-UTR) was quite similar to that based on the sequences of the capsid-coding (VP1) region of the same viruses. The existence of two distinct lineages of type Asia1 suggested by the study on the VP1 region was further supported by the detection of a difference in length and predicted secondary structure of the 5'LF-UTR between the two lineages. Sequence variability between the isolates of the two lineages was also observed within the different domains of the internal ribosome entry site (IRES) around conserved motifs like the GNRA,- RAAA,- and the polypyrimidine tract. Certain group and lineage-specific signature nucleotides pertaining to FMDV type Asia1 in the 5'LF-UTR have been identified. The present study shows that the 5'LF-UTR of FMDV serotype Asia1 field isolates are variable in relation to the length and probable secondary structure of the IRES.

5' Untranslated Regions↗

Induction of immunity in swine by purified recombinant VP1 of foot-and-mouth disease virus.

VP1, a capsid protein of foot-and-mouth disease virus (FMDV), contains neutralizing epitopes of the virus. Due to its poor water solubility, recombinant Escherichia coli derived VP1 (rVP1) has previously been used mainly in a denatured form and is not well characterized. Here, using SDS to assist protein refolding and then removing SDS with a detergent removing column, we have successfully purified rVP1 in two aqueous-soluble forms, i.e. monomer and dimer. Studies showed that dimerization occurs by an inter-molecular disulfide bond between two cysteine residues at position 187 of each monomer. Heat treatment revealed that rVP1 dimer exhibited a more thermal-stable conformation than the monomeric form. Both monomeric and dimeric rVP1 reacted with anti-FMDV antibodies. Immunization studies demonstrated that vaccination of swine with either forms of rVP1 was effective in generating immune responses and protecting them from viral challenge.

Amino Acid Sequence↗

Sensitivity of primary cells immortalised by oncogene transfection for the detection and isolation of foot-and-mouth disease and swine vesicular disease viruses.

Primary cells derived from calf thyroid (CTY), calf kidney (CK) and piglet kidney (PK) were immortalised by oncogene transfection and their susceptibility to infection by foot-and-mouth disease (FMD) virus and swine vesicular disease (SVD) virus examined. Eighty-five immortalised cell lines (47 CTY, 20 CK and 18 PK) proved stable upon repeated cell culture passage and many supported the growth of FMD virus and several of the PK cell lines supported SVD virus. However, none of the immortalised lines exhibited either the degree of sensitivity or the specificity for all virus serotypes and strains as shown by primary CTY and IB-RS-2 cell cultures which are routinely employed for vesicular virus diagnosis.

Animals↗

Evaluation of in vitro inhibitory potential of small interfering RNAs directed against various regions of foot-and-mouth disease virus genome.

India is endemic for foot-and-mouth disease and it continues to be a major threat to the livestock industry despite vaccination programmes. In the present study, the ability of specific small interfering (si)RNAs directed against different genomic regions of foot-and-mouth disease virus (FMDV) to inhibit virus replication in BHK-21 cells was examined. For preliminary evaluation of possible siRNA-mediated FMDV inhibition, a cocktail of several unique populations of 12-30bp siRNAs were successfully produced corresponding to three target regions located at structural (VP3-VP1), non-structural (2A-2C), and non-structural-untranslated (3D-3'UTR) region of serotype Asia1. Once the populations of siRNAs generated were found to reduce the virus titre significantly, two highly conserved 21bp siRNA duplexes were designed by analysing all FMDV sequence entries available in public-domain databases. In virus titration assay, more than 99% inhibition of virus yield for all the four serotypes (type Asia1, O, A, and C) could be demonstrated in cells transfected with each of the FMDV-specific siRNAs at 24h post-infection, compared to control cells transfected with scrambled siRNA. This was well supported by reduction in OD values in FMDV-specific sandwich ELISA. Although 100-fold reduction in virus titre with siRNA1 is substantial considering the transfection efficiency and fixed level of input siRNA, siRNA2 emerged to be a better choice as target where more than 300-fold reduction was observed and its inhibitory effect extended up to 48 h post-infection against all the serotypes. Interestingly, in the present study type A virus (IND 17/77) had a single mismatch at position 2 in the siRNA2 target region but it did not abrogate the inhibitory effect.

Animals↗

Action of FAO in the control of foot and mouth disease.

This paper describes the role played by FAO in the control of foot and mouth disease. Since 1954 the FAO European Commission for the control of foot-and-mouth disease co-ordinated the regional programme for eradication of FMD in Europe. One of the major achievements of the Commission has been to prevent the introduction and spread of exotic strains of foot and mouth disease into Europe through the Balkans. FAO also supports the activities of the Foot-and-Mouth Disease World Reference Laboratory located in the Institute of Animal Health, Pirbright, UK. The Infectious Diseases/EMPRES Group of the Animal Health Service, Animal Production and Health Division of FAO, promotes a global approach to the control and eradication of transboundary animal diseases over the world. For foot and mouth disease, the strategy is based on co-ordinated regional programmes. For FAO, no sustainable progress can be achieved in FMD control over the world without addressing and supporting the control of the disease in endemic countries.

Animals↗

Innate immune responses following emergency vaccination against foot-and-mouth disease virus in pigs.

Inactivated "emergency" foot-and-mouth disease virus (FMDV) vaccine of high potency will induce early protection against the disease, implying a critical role for innate immune defences. At 3 and 6 days post-vaccination (dpv), there was no evidence of vaccine-induced specific anti-FMDV antibodies (Abs), nor enhanced uptake and destruction of opsonised virus by macrophages. Sera from vaccinates and control animals showed similar capacity to neutralise the virus, and were not different from the pre-vaccination sera. There were also no distinguishable changes in the distribution of the different peripheral blood leucocyte (PBL) subpopulations. Nor was any vaccine-induced increase in production of acute phase proteins noted. In contrast, chemotaxis assays identified an increase in PBL migratory activity which was vaccine-related. Furthermore, sera from 3 days post-vaccination contained elevated chemotactic potential. These results demonstrate that enhanced chemotaxis of cells of the innate immune defences, could play an important role during the early protection induced by emergency FMDV vaccines.

Acute-Phase Proteins↗

Developments in foot-and-mouth disease vaccines.

The current status of foot-and-mouth disease (FMD) vaccine production is reviewed. The production of antigen in bovine tongue epithelium (Frenkel culture) is described and improvements in monolayer and suspension cultures of cell lines are outlined. Inactivation of viral antigen and safety tests are discussed. A 'minimum safety level' is recommended: at the end of the inactivation process, antigen batches of any size should contain less than one virus particle. After inactivation the antigen can be formulated into a vaccine or purified and concentrated for storage at ultra-low temperatures in a vaccine bank. Vaccines prepared with the adjuvants Al(OH)3 and saponin are compared with (double) oil emulsion vaccines. Because oil vaccines can protect both cattle and pigs and induce long-term protection, they are most suitable for use in ring vaccinations. A new generation of vaccines, based on constructed modified-live viruses or (bio-) synthetic peptides, is briefly reviewed.

Animals↗