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PubMed1990

Genetic and phenotypic variability during replication of foot-and-mouth disease virus in swine.

A plaque-purified preparation of foot-and-mouth disease virus (FMDV) of serotype C1 (C-S8c1-1), grown in cell culture, was used to infect nonimmunized pigs. No variant genomes were detected in the average populations of 50 viruses isolated from infected animals by direct RNA sequencing of the carboxy-terminal half of the VP1 gene. However, a mutant with altered phenotypic properties was present in low proportion in an infected animal. The frequency of mutants resistant to neutralization by SD6 monoclonal antibody (MAb) [SD6 epitope MAb-resistant mutants (MARMs)], directly estimated in virus from lesions of infected animals (without passage in cell culture), depended on the procedure used for its determination and ranged from 2.9 x 10(-6) (when the virus was incubated with the MAb prior to plating) to 2.6 x 10(-5) (when incubation with MAb was avoided and the MAb was maintained in the agar overlay of the titration assay). Such a difference was not found for C-S8c1-1, which consistently showed frequencies of about 4 x 10(-5). In addition, the repertoire of amino acid substitutions was similar among SD6 epitope MARMs isolated directly both from vesicles of infected animals and from C-S8c1-1. Thus, in spite of the conservation of the average sequence in the region of VP1 RNA analyzed, antigenic heterogeneity has been found in viral populations of FMDV upon replication in nonimmunized swine.

Animals↗
PubMed2000

Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in Taiwan, 1998.

A large scale outbreak of hand-foot-and-mouth disease (HFMD) occurred in Taiwan in 1998, in which more than 80 children died of shock syndrome with pulmonary edema/hemorrhage. Enterovirus 71 was implicated as the cause of this outbreak. In order to understand the virological basis responsible for mortality on this scale, nucleotide sequences of VP1 that is important for serotypic specificity, and the 5'-non-coding region (5'-NCR) that is important for replication efficiency, were analyzed comparatively. Phylogenetic analysis of both VP1 and 5'-NCR of nine EV71 isolates derived from specimens of fatal patients and seven isolates derived from uncomplicated HFMD patients showed that all but one isolate fell into genotype B. The one distinct isolate from a case of uncomplicated HFMD belonged to genotype C that was clustered along with one isolate from Taiwan in 1986. Complete sequence analysis of two selected isolates, one from the spinal cord of a fatal case and one from the vesicle fluid of a patient with mild HFMD, confirmed a high degree (97-100%) of identity in nucleotide sequence throughout the entire genome, except focal regions of 3C and 3'-NCR where the nucleotide homology was 90-91%. The identity of the deduced amino acid sequence in the 3C region that encodes viral proteinase dropped further to 86%, a result of missense mutations at the first nucleotide position of many codons.

5' Untranslated Regions↗
PubMedDate not supplied

Epidemiological characteristics and financial costs of the 1997 foot-and-mouth disease epidemic in Taiwan.

Between March and July 1997, a devastating outbreak of foot-and-mouth disease (FMD), serotype O, occurred in pigs in Taiwan. A total of 6,147 pig farms with more than 4 million pigs were infected, and 37.7 per cent of the pigs in Taiwan either died (0.18 million pigs) or were killed (3.85 million pigs). The epidemic reached its peak during the fifth week after it was first recognised. During the eighth and ninth weeks, a two-dose blanket vaccination programme was instituted which led to a large reduction in new outbreaks. Except for two cities, the whole of Taiwan was declared an FMD-infected zone. During the four months in which new farm outbreaks occurred, 21.7 per cent of the pigs on infected farms showed clinical signs, and there was an overall mortality of 3.95 per cent. During the early stages of the epidemic, the incubation period was as short as 24 hours and the case fatality rates for suckling piglets reached 100 per cent. The financial cost of the epidemic was estimated at US$ 378.6 million, including indemnities, vaccines, carcase disposal plus environmental protection, miscellaneous expenses, and loss of market value. Owing to the ban on exports of pork to Japan, it is estimated that the total economic cost to Taiwan's pig industry will be about US$ 1.6 billion.

Animal Husbandry↗
PubMed2002

Estimating the risk of importation of foot-and-mouth disease into Europe.

The opinions of a number of recognised world experts on foot-and-mouth disease (FMD) were sought in order to answer key questions relating to the importation of the disease into European countries from countries outside Europe. In addition, their opinions were sought on where in Europe a primary outbreak of FMD was most likely to occur and the number of outbreaks likely to occur within European countries in the next five years. The Balkans group of countries was considered to be the most likely group within Europe to have a primary outbreak of FMD and also most likely to have the highest number of primary outbreaks. Turkey was considered to be the country outside Europe which was most likely to be the source of an outbreak within Europe as a whole, and the illegal importation of livestock was considered to be the most likely route of introduction of FMD into Europe. Results specific to the Islands group of countries, which included the UK and Ireland, suggested that this group was likely to have a mean of one primary outbreak of FMD in the five years from September 2000, and that the importation of foodstuffs by people entering those countries from Turkey was the most likely source of an outbreak.

Animals↗
PubMed2006

Presence of antibodies to non-structural proteins of foot-and-mouth disease virus in repeatedly vaccinated cattle.

For the purpose of removing infected animals by detecting humoral immune responses to non-structural proteins of the foot-and-mouth disease (FMD) virus, antibodies induced by contaminated residual non-structural proteins contained in less pure FMD vaccine can be problematic for serological screening. The aim of the present study was to measure the possible presence of antibodies against these non-structural proteins in repeatedly vaccinated calves and beef cattle. Five imported FMD vaccines were examined using two commercial ELISA kits, UBI FMDV NS EIA and Ceditest FMDV-NS, for serological testing. After five doses of vaccination, the serum of one calf tested positive, and two vaccines induced a significant increase in anti-3ABC antibodies in calves. This finding demonstrated that a positive reaction to non-structural proteins due to impurities in the FMD vaccine was detectable using commercial tests. A low percentage of field sera sampled from beef cattle in Kinmen also tested positive, but the key factor resulting in the positive reactions could not be positively identified based on our data.

Animals↗
PubMed1980

Location of the initiation site for protein synthesis on foot-and-mouth disease virus RNA by in vitro translation of defined fragments of the RNA.

An mRNA-dependent reticulocyte lysate has been used to translate foot-and-mouth disease virus RNA in vitro. Polypeptides P16, P20a, and P88, which have been shown to be derived from the 5' end of the RNA by pactamycin mapping experiments with infected cells, were preferentially synthesized in vitro. Removal of VPg, the small protein covalently linked to the 5' end of the genome RNA, had no effect on the translation of the RNA. The two RNA fragments (L and S) produced by specific digestion of the polycytidylic acid [poly(C)] tract with RNase H were also translated in vitro. The L fragment, consisting of RNA to the 3' side of the poly(C) tract and including the polyadenylic acid [poly(A)] tract, directed the synthesis of the same products as those made by full-length RNA. However, no small defined products were produced when the S fragment, which contains the 5' end of the RNA, was translated. These results show that the major initiation site for protein synthesis on foot-and-mouth disease virus RNA is to the 3' side of the poly(C) tract. Furthermore, the use of N-formyl [35S]methionine tRNAfMet as a label for the initiation peptides showed that the major polypeptide labeled in lysates primed with both full-length RNA and the L fragment was P16, i.e., the protein nearest the initiation site for translation as deduced from pactamycin mapping experiments. Fragments of RNA were also translated in vitro. Those containing the poly(C) tract gave products similar to those produced when full-length RNA was translated. The polypeptides synthesized when fragments containing the poly(A) tract were used, however, did not resemble those made from full-length RNA.

Aphthovirus↗
PubMed1978

Cross reaction between bovine enterovirus and South African Territories I5 foot-and-mouth disease virus.

A bovine enterovirus (E76T) isolated from a 2-year-old bull produced serologic cross reactions to South African Territories (SAT) I5 foot-and-mouth disease virus when inoculated into guinea pigs and cattle. Cross-reacting serum titers to SAT I5 virus of 1:320 by the plaque-reduction neutralization test and 1:20 by the radial immunodiffusion test occurred in 2 steers after they were inoculated with the E76T virus. In 1 steer, maximal cross-reacting titers appeared related to a 2nd exposure to the viruses or to a hyperimmune state. Ultracentrifugation and 2-mercaptoethanol studies indicated that the cross reactions were due to immunoglobulin M antibody. Sera from guinea pigs immunized with the E76T or the SAT I5 virus cross reacted with the heterologous virus by postinoculation day 7. Cross-reacting titers had decreased markedly by postinoculation day 35, whereas the homologous virus titer remained constant. Cross reactivity of the E76T virus was primarily with the SAT I5 virus, and to a lesser degree with SAT II3. Cross reactions did not occur with representatives of the 5 other antigenic types of foot-and-mouth disease virus.

Animals↗
PubMed1989

Novel low-molecular-weight synthetic vaccine against foot-and-mouth disease containing a potent B-cell and macrophage activator.

Most synthetic peptide vaccines described to date are effective only in combination with proteins and Freund's adjuvant. The work describes a novel completely synthetic virus peptide vaccine, which consists of a synthetic activator of B cells and macrophages, covalently linked to an amphiphilic alpha-helical T-cell epitope. The low-molecular-weight vaccine of 3.4 kDa developed against foot-and-mouth disease virus (FMDV) is composed of a synthetic VP1 (135-154) with a sequence homologous to an FMDV protein and the adjuvant tripalmitoyl-S-glyceryl-cysteinylserylserine (P3CSS). P3CSS is the synthetic analogue of the N-terminal part of the lipoprotein from Gram-negative bacteria. The antigenic determinant VP1 (135-154) is an alpha-helix as shown by circular dichroism. The resulting novel type of vaccine tripalmitoyl-S-glyceryl-cysteinylserylseryl-FMDV-VP1 (135-154) induces a long-lasting high protection against foot-and-mouth disease and serotype-specific virus-neutralizing antibodies in guinea-pigs after a single administration without any additional adjuvant or carrier. In contrast to other simple fatty acid conjugates this new type of vaccine contains a built-in adjuvant with high affinity to both B and T lymphocytes.

Adjuvants, Immunologic↗
PubMed1994

Emergency vaccination against foot-and-mouth disease: rate of development of immunity and its implications for the carrier state.

Emergency foot-and-mouth disease (FMD) vaccines prepared from antigens held in the International Vaccine Bank at Pirbright were administered to cattle and pigs and the levels of protection were assessed following challenge by contact with infected pigs. Both Al(OH)3/saponin and oil-based cattle vaccines proved to be extremely effective and protected soon after vaccination (4 days postvaccination), whereas the pigs were seldom protected before 21 and 28 days postvaccination, probably due to lower levels of antibody and overwhelming challenge conditions. Early production of cattle occurred in the absence of significant levels of circulating antibody as measured by enzyme-linked immunosorbent assay, a neutralization assay and a passive protection test. A large number of the cattle vaccinated with the O1 Lausanne strain of FMD and subsequently challenged with this virus became persistently infected and there appeared to be a correlation with the time interval between vaccination and challenge. When the same cattle were vaccinated approximately 4 months later with a different strain of FMD, C1 Oberbayern, and challenged with this strain, the number of persistently infected animals was considerably lower. The results are discussed in the context of the use of emergency vaccines to prevent the dissemination of FMD from disease foci.

Animals↗
PubMed2003

Modeling alternative mitigation strategies for a hypothetical outbreak of foot-and-mouth disease in the United States.

Alternative mitigation strategies were compared during hypothetical outbreaks of foot-and-mouth disease (FMD) in the USA using a computer-simulation model. The epidemiologic and economic consequences were compared during these simulated outbreaks. Three vaccination and four slaughter strategies were studied along with two speeds of FMD virus spread among three susceptible populations of animals. The populations represented typical animal demographics in the United States. The best strategy depended on the speed of spread of FMD virus and the demographics of the susceptible population. Slaughter of herds in contact with known contagious herds was less costly than slaughtering only contagious herds. Slaughtering in 3 km rings around contagious herds was consistently more costly than other slaughter strategies. Ring vaccination in 10 km rings was judged more costly than slaughter alone in most situations. Although early ring vaccination resulted in lower government costs and duration in fast-spread scenarios, it was more costly when vaccinated animals were slaughtered with indemnity and other related slaughter costs.

Abattoirs↗
PubMed1983

Differential significance of epizootiological factors in the control of foot-and-mouth disease. A brief review.

The discovery of respiratory tract involvement in the pathogenesis of foot-and-mouth disease (FMD) and the recognition of the role of inhalated aerosols in virus transfer opened new outlooks in the epizootology and prophylaxis of the disease. Nevertheless, FMD should be regarded for an infection transmitted by contaminated passive vectors including man and stable equipment. Transient persistence of FMD virus in the upper respiratory airways of cattle is of interest, but there is no reason to consider this for a significant hazard. Regular annual immunization with a vaccine containing the most isolated virus serotypes seems to be the best way how to prevent epizootics and panzootics.

Aerosols↗
PubMed2002

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↗
PubMed2003

Expression of foot-and-mouth disease virus epitopes in tobacco by a tobacco mosaic virus-based vector.

We expressed two immunogenic dominant epitopes of foot-and-mouth disease virus (FMDV) serotype O in tobacco plant using a vector based on a recombinant tobacco mosaic virus (TMV). The recombinant viruses TMVF11 and TMVF14 contained peptides of 11 and 14 amino acid residues, respectively, from FMDV VP 1 fused to the open reading frame of TMV coat protein (CP) gene between amino acid residues 154 and 155. TMVF11 and TMVF14 systemically infected tobacco plant and produced large quantities of stable progeny viral particles assembled with the modified CP subunits. Guinea pigs, mice and swine were used to test the protective effects of the recombinant viruses against FMDV infection. Most guinea pigs were protected against FMDV challenge after parenteral injection with TMVF11, TMVF14, or the mixture TMVF11/TMVF14, but not wtTMV. The TMVF11/TMVF14 mixture protected all animals when challenged with 150 guinea pig 50% infection dosage (GPID(50)) FMDV. Oral administration of the TMVF11/TMVF14 mixture (3mg total) protected 3/8 guinea pigs against the same FMDV challenge. Most of the suckling mice parenterally injected with antiserum from guinea pigs immunized with the TMVF11/TMVF14 mixture, but not with wtTMV, were also protected against FMDV challenge with 10 suckling mouse 50% lethal dosage (SMLD(50)), indicating that antibodies produced in guinea pigs immunized with the TMVF11/TMVF14 mixture specifically neutralized FMDV. Western blot analysis indicated that antiserum from those guinea pigs reacted with the FMDV VP1 protein. The protective effect of TMVF11 was also demonstrated in swine, where preliminary tests showed that nine pigs immunized with TMVF11 in three experiments were protected against FMDV challenge with 20 minimal infecting dose (MID).

Animals↗
PubMed1982

An outbreak of hand, foot, and mouth disease in Singapore.

Epidemiological studies were carried out during an extensive outbreak of hand, foot and mouth disease caused by coxsackievirus A 16 in Singapore in 1981. Most of the cases were concentrated in densely populated public housing estates, and the morbidity rate was highest in children under 5 years of age. The mean secondary attack rate for children under 12 years of age was 76.7% compared with an overall rate of 31.3%. The incubation period ranged from 1 to 7 days. Factors favouring the transmission of infection within a household included sharing of household and personal articles with the index case. The disease was mild and self-limiting.

Adolescent↗
PubMed2006

Development of an inhibition ELISA test for the detection of non-capsid polyprotein 3ABC in viral suspensions destined for inactivated foot-and-mouth disease vaccines.

The use during the last decade of immuno-enzymatic tests based on the detection of antibodies to the non-capsid proteins (NCPs) of foot-and-mouth disease virus (FMDV) to assess viral circulation, irrespective of vaccination, supported the incorporation into the OIE code of the 'free from FMDV with vaccination' category and opened the way to a 'vaccination to live' policy. Eradication programmes in South America include systematic vaccination accompanied by large serosurveys through NCP antibody testing to ensure the absence of residual viral activity. For correct interpretation of serosurveys, a major prerequisite is that vaccines made of semi-purified preparations of inactivated virions do not contain levels of NCPs, which upon proper presentation conditions, could induce an antibody response under the conditions for field immunization. This work describes the development of an inhibition ELISA to detect NCP polyprotein 3ABC in viral suspensions destined for vaccine production as an in-process control during vaccine manufacture. Antibody responses against NCP 3ABC in vaccinated and revaccinated cattle, induced by vaccines with different purification processes and formulations, are discussed.

Animals↗
PubMed1987

Correlation of 140S antigen dose with the serum neutralizing antibody response and the level of protection induced in cattle by foot-and-mouth disease vaccines.

An analysis was made of data from potency tests on fifteen batches of monovalent foot-and-mouth disease vaccine, comprising five batches each of type O, type A and type C. Regressions were calculated for the relation of percentage protection (probit) versus log 140S antigen dose and for the serum neutralizing antibody titre (log SN50) versus log 140S antigen dose. Type O vaccines required a far higher level (220 ng) of 140S antigen to achieve a 50% protection level (PA50) in cattle than did type A (2.4 ng) and type C (4.36 ng) vaccines. Type O antigen, dose for dose, was as effective at provoking neutralizing antibody as the types A and C antigens. Thus, it would appear that a far higher log SN50 value (2.14) was required for type O vaccines to equate with 50% protection of cattle than was required for type A (1.17) and type C (1.41) vaccines. Prior to 1977, however, the PA50 value for type O vaccine strain was only 1.34 and it was concluded that an antigenic shift was the most likely cause for the large difference between that value and the current PA50 value.

Animals↗