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PubMed1983

Antibody response in bovine pharyngeal fluid following foot-and-mouth disease vaccination and, or, exposure to live virus.

Samples of pharyngeal fluid and serum were collected from cattle after exposure to live foot-and-mouth disease (FMD) virus (with or without prior vaccination) or after subcutaneous vaccination with inactivated virus. The pharyngeal fluid samples were examined for FMD neutralising activity and specific anti-FMD IgG, IgM and IgA antibodies. The neutralising activity of the serum was also monitored. A peak of neutralising activity which occurred in the pharyngeal fluid of unvaccinated cattle seven days after virus exposure corresponded to a rise in specific IgM and IgA antibodies. This peak appeared to be due to serum and tissue fluid escaping from the damaged mucosa during the acute inflammatory phase of infection. At later stages (20 to 60 days after virus exposure) the pharyngeal fluid neutralising activity corresponded to a rise in specific IgA antibodies, suggesting that active local antibody production was taking place. The pharyngeal fluid neutralising activity detected after revaccination with oil emulsion or aqueous vaccines, without exposure to live virus, corresponded to a rise in specific IgG and IgM antibody levels and this may have been due to serum transudation.

Animals↗
PubMed2006

Genetic diversity of coxsackievirus A16 associated with hand, foot, and mouth disease epidemics in Japan from 1983 to 2003.

To clarify the chronologic genetic diversity of coxsackievirus A16 (CV-A16) strains associated with hand, foot, and mouth disease (HFMD) epidemics in a restricted area and their genetic relation with those isolated in other areas, we investigated the genetic diversity of the 129 CV-A16 strains associated with HFMD epidemics in Fukushima, Japan, from 1983 to 2003, and compared their genetic relation to 49 CV-A16 strains isolated in other areas of Japan and in China by using phylogenetic analysis based on the VP4 sequences. Phylogenetic reconstruction of the CV-A16 strains isolated in Fukushima from 1983 to 2003 demonstrated three distinct genetically divergent clusters related to HFMD epidemics that occurred from 1984 to 1994 (including the 1985 and 1991 outbreaks), HFMD epidemics from 1987 to 1998 (including the 1988 and 1998 outbreaks), and HFMD epidemics from 1995 to 2003 (including the 1995 and 2002 outbreaks). CV-A16 strains isolated during each period in Fukushima formed a single cluster with those isolated during essentially the same time period in other areas of Japan and in China. Our results demonstrated that prevalent CV-A16 strains causing HFMD in Fukushima, Japan, genetically changed twice during 21 epidemics, and changes were also observed in the CV-A16 strains causing HFMD epidemics in other areas. We concluded that repeated outbreaks of CV-A16-related HFMD in Japan were caused, in part, by the introduction of genetically changed CV-A16 strains, which might be transmitted overseas.

Animals↗
PubMed2002

A decision-tree to optimise control measures during the early stage of a foot-and-mouth disease epidemic.

A decision-tree was developed to support decision making on control measures during the first days after the declaration of an outbreak of foot-and-mouth disease (FMD). The objective of the tree was to minimise direct costs and export losses of FMD epidemics under several scenarios based on livestock and herd density in the outbreak region, the possibility of airborne spread, and the time between first infection and first detection. The starting point of the tree was an epidemiological model based on a deterministic susceptible-infectious-recovered approach. The effect of four control strategies on FMD dynamics was modelled. In addition to the standard control strategy of stamping out and culling of high-risk contact herds, strategies involving ring culling within 1 km of an infected herd, ring-vaccination within 1 km of an infected herd, and ring-vaccination within 3 km of an infected herd were assessed. An economic model converted outbreak and control effects of farming and processing operations into estimates of direct costs and export losses. Ring-vaccination is the economically optimal control strategy for densely populated livestock areas whereas ring culling is the economically optimal control strategy for sparsely populated livestock areas.

Animal Husbandry↗
PubMed1999

Isolation of subgenus B adenovirus during a fatal outbreak of enterovirus 71-associated hand, foot, and mouth disease in Sibu, Sarawak.

BACKGROUND: In mid-1997, several children died in Sarawak, Malaysia, during an epidemic of enterovirus-71 (EV71) hand, foot, and mouth disease. The children who died had a febrile illness that rapidly progressed to cardiopulmonary failure and the cause was not satisfactorily resolved. We describe the isolation and identification of a subgenus B adenovirus from the children who died. METHODS: We studied two groups of children presenting to Sibu Hospital from April 14 to Sept 30, 1997. For children who died, the inclusion criterion was death after febrile illness, and for those who did not die it was acute flaccid paralysis (AFP). Serum and cerebrospinal fluid samples were tested for IgM antibodies to Japanese encephalitis and dengue viruses. Viruses isolated were identified by immunofluorescence, reverse-transcriptase PCR, or PCR and DNA sequencing. FINDINGS: Enterovirus was isolated in three (19%) of 16 children who died and in none of the eight surviving children with AFP. However, an agent that was initially difficult to identify was found in ten (63%) children who died and five (63%) surviving children who had AFP. The agents isolated from ten (66.7%) of these 15 children were eventually identified as adenoviruses and were isolated mainly from clinically important sterile sites or tissues. All the enterovirus-positive children who died had this second agent. INTERPRETATION: Our data raises doubts that EV71 was the only aetiological agent in these deaths.

Adenoviridae↗
PubMed1988

Response to foot-and-mouth disease vaccines in newborn calves. Influence of age, colostral antibodies and adjuvants.

Oil-emulsified (OE) and aqueous (Aq) vaccines were prepared with the same batch of inactivated A24 8345 foot and mouth disease virus (FMDV). Calves born to vaccinated dams did not respond to the Aq vaccine 30 or 90 days post partum. When the OE vaccine was used on a similar group of calves, no responses were elicited up to 21 days post partum. However, calves 30 or more days old responded like adult cattle to the OE vaccine. When the OE vaccine was used in colostral antibody-free calves 3-30 days old, all animals showed good antibody responses but, in calves vaccinated 3 or 7 days post partum, antibodies were detectable only after a considerable period of time. Our results show that both passively acquired colostral antibodies and age are important in the response of very young calves to FMDV oil vaccines. From a practical point of view, in endemic areas where adult cattle are periodically vaccinated, vaccination of calves between 30 and 60 days post partum with OE vaccines would lead to high levels of herd protection.

Adjuvants, Immunologic↗
PubMed1997

Molecular analysis of foot-and-mouth disease type O viruses isolated in Saudi Arabia between 1983 and 1995.

Partial nucleotide sequence of the capsid polypeptide coding gene 1D (VP1) was determined for 68 serotype O foot-and-mouth disease viruses isolated between 1983 and 1995 from outbreaks occurring in Saudi Arabia. The sequences were compared with previously published sequences: 14 viruses of Middle Eastern origin (isolated between 1987 and 1991); and with four vaccine virus strain sequences, three originating from the Middle East (O1/Turkey/Manisa/69, O1/Sharquia/Egypt/72 and O1/Israel/2/85) and one from Europe (O1/BFS 1860/UK/67). The virus isolates from Saudi Arabia and the Middle East vaccine virus strains formed a related genetic group distinct from the European O1 virus. Within this large group 12 distinct genetic sublineages were observed.

Animals↗
PubMed1975

The pathogenicity of bovine strains of foot and mouth disease virus for impala and wildebeest.

Impala (Aepyceros melampus) and wildebeest (Connochaetes taurinus) were infected with bovine strains of foot and mouth disease virus by intradermolingual inoculation. No clinical signs developed in the impala but mild atypical lesions developed in the tongues of the wildebeest with generalized spread to one foot in two of the eight animals exposed. All the impala but only some of the wildebeest developed viraemia. No virus could be isolated from any tissues in either species after the 7th day following virus inoculation. Immune response occurred in both species. A field survey revealed few animals of either species with significant antibody titers and no virus 'carriers' were found.

Animals↗
PubMed2000

An immunoglobulin G based chimeric protein induced foot-and-mouth disease specific immune response in swine.

Epitopes containing the residues 141aa-160aa and 200aa-213aa from foot-and-mouth disease (FMD) serotype O1K HK type FMDV VP1 were joined to a swine immunoglobulin G single heavy chain constant region (scIgG), creating a novel chimeric protein, named F1-scIgG. In this study, inoculation with F1-scIgG induced both FMD virus-neutralizing antibody response and T cell response in swine. Antisera from these F1-scIgG-inoculated swine protected suckling mice against 1000 lethal dose 50 (1000LD(50)) FMD challenge. F1-scIgG-inoculated swine were also fully protected against 50LD(50) FMD virus challenge. The present study demonstrates the clear potential for viral epitopes linked with self-Ig in novel FMD vaccine design.

Animals↗
PubMed1990

Detection of foot-and-mouth disease virus by competitive ELISA using a monoclonal antibody specific for the 12S protein subunit from six of the seven serotypes.

Foot-and-mouth disease (FMD) prevention and control programs are dependent upon rapid, reliable diagnostic procedures. The widely used FMD diagnostic complement fixation (CF) procedures require a specific antiserum for each of the seven FMDV serotypes making the tests both cumbersome and difficult to standardize. An FMD diagnostic, monoclonal antibody based inhibition-ELISA procedure was developed. The test uses a single monoclonal antibody (MAb) that reacts with all European and South American FMDV isolates examined. The procedure detects a highly conserved epitope on the 12S protein subunit of FMDV which appears to be common to all FMDV's with the exception of the South African Territories 2 serotype. The results indicate that the sensitivity of this test is greater than CF and approaches that of virus isolation.

Animals↗
PubMed1980

The response of some African wildlife species to foot-and-mouth disease vaccination.

The preservation of wildlife is of increasing importance in may countries in Africa but, due to hazards of possible transmission of disease from wild to domesticated species, the interests of the conservationist can conflict with those of the livestock owner. Foremost among transmissible diseases common to many species of both wild and domesticated animals is foot-and-mouth disease (FMD). The effects of FMD vaccination on three important wildlife species, African buffalo (Syncerus caffer), eland (Taurotragus oryx) and impala (Aepyceros melampus), are described. The pattern of response in all three species was similar to that of cattle but of a lower order. The implications are discussed and a vaccination protocol is suggested.

Africa↗
PubMed1994

Immunogenicity of non-structural proteins of foot-and-mouth disease virus: differences between infected and vaccinated swine.

Non-structural as well as VP1 recombinant proteins of foot-and-mouth disease virus (FMDV) produced in E. coli, have been used to study the specific antibody response of infected or vaccinated swine. An analysis of sera from infected pigs, using a direct ELISA, showed that polypeptide 3ABC (spanning non-structural proteins 3A, 3B and 3C) was the most antigenic among the recombinant proteins studied and allowed specific detection of FMDV infected swine from the second week after the infection. The sensitivity of this assay was comparable to that obtained when the whole FMDV was used as ELISA antigen. Conversely, use of polypeptide 3ABC did not allow detection of significant levels of antibodies in sera from vaccinated animals. This differential pattern of ELISA reactivities offers a promising approach for the distinction of infected from vaccinated pigs. In addition, a highly specific and sensitive method of diagnosis for FMDV replication was achieved using an immunoblotting assay which detected antibodies against the 3ABC polypeptide.

Animals↗
PubMed2005

Development of transgenic alfalfa plants containing the foot and mouth disease virus structural polyprotein gene P1 and its utilization as an experimental immunogen.

The use of transgenic plants as vectors for the expression of viral and bacterial antigens has been increasingly tested as an alternative methodology for the production of experimental vaccines. Here, we report the production of transgenic alfalfa plants containing the genes encoding the polyprotein P1 and the protease 3C of foot and mouth disease virus (FMDV). The immunogenicity of the expressed products was tested using a mouse experimental model. Parenterally immunized mice developed a strong antibody response and were completely protected when challenged with the virulent virus. This report demonstrates the possibility of using transgenic plants to express polyprotein P1 and the protease 3C of FMDV and their utilization as effective experimental immunogens.

Agrobacterium tumefaciens↗
PubMed1970

Detection of foot-and-mouth disease virus antibodies. I. "Passive" hemagglutination test.

A passive hemagglutination test has been developed to detect and measure foot-and-mouth disease virus (FMDV) antibody by using glutaraldehyde as a coupling reagent. An optimal concentration of 10 to 40 mug of virus per ml with 0.25% glutaraldehyde at 25 C for 1 hr was established for the sensitization of sheep erythrocytes. A reaction time of 18 hr at 4 C or 2 hr at 37 C induced good agglutination in the presence of specific antibody. Sensitization was carried out in phosphate buffer, whereas agglutination and preadsorption of nonspecific agglutinins from sera were performed in gelatin (0.1%, w/v)-stabilized, phosphate-buffered saline. An optimal pH of 7.2 was also established for all reactions. Antibodies derived from guinea pigs hyperimmunized by infecting with FMDV, types A, O, and C were both virus-and type-specific. Preliminary experiments showed that strain A-119 and strain A-24 Cruzeiro could also be distinguished by hemagglutination. Parallel hemagglutination and complement-fixation tests showed the former to be two to four times more sensitive than the latter.

Aldehydes↗
PubMed1997

Baculovirus expressed 2C of foot-and-mouth disease virus has the potential for differentiating convalescent from vaccinated animals.

Determining whether animals have been infected with foot-and-mouth disease virus or vaccinated is important because infected animals frequently become carriers of the virus, shed it intermittently and thus may be the source of new outbreaks of the disease. We had shown previously that the sera of convalescent animals contain antibodies to 2C, a highly conserved non-structural protein, whereas the sera of vaccinated animals do not. This is explained by observation that 2C is retained on the membranes of cells used for growing the virus for vaccine production. In contrast, the non-structural protein 3D, which is released into the medium, is not removed by centrifugation or filtration during vaccine production and therefore stimulates an immune response in both vaccinated and convalescent cattle. In this study we produced 2C and 3D in insect cells infected with recombinant baculoviruses. As demonstrated by serology and electron microscopy, 2C is also retained on the membranes of the insect cells. Both expressed proteins react with sera of convalescent animals, indicating that they are conformationally similar, but the 2C does not react with sera from vaccinated animals. The baculovirus expressed 2C appears to be a suitable antigen for the development of a reliable diagnostic test.

Animals↗
PubMed2000

Interspecies major histocompatibility complex-restricted Th cell epitope on foot-and-mouth disease virus capsid protein VP4.

T-cell epitopes within viral polypeptide VP4 of the capsid protein of foot-and-mouth disease virus were analyzed using 15-mer peptides and peripheral blood mononuclear cells (PBMC) from vaccinated outbred pigs. An immunodominant region between VP4 residues 16 and 35 was identified, with peptide residues 20 to 34 (VP4-0) and 21 to 35 (VP4-5) particularly immunostimulatory for PBMC from all of the vaccinated pigs. CD25 upregulation on peptide-stimulated CD4(+) CD8(+) cells-dominated by Th memory cells in the pig-and inhibition using anti-major histocompatibility complex class II monoclonal antibodies indicated recognition by Th lymphocytes. VP4-0 immunogenicity was retained in a tandem peptide with the VP1 residue 137 to 156 sequential B-cell epitope. This B-cell site also retained immunogenicity, but evidence is presented that specific antibody induction in vitro required both this and the T-cell site. Heterotypic recognition of the residue 20 to 35 region was also noted. Consequently, the VP4 residue 20 to 35 region is a promiscuous, immunodominant and heterotypic T-cell antigenic site for pigs that is capable of providing help for a B-cell epitope when in tandem, thus extending the possible immunogenic repertoire of peptide vaccines.

Amino Acid Sequence↗
PubMed2001

A single amino acid substitution in nonstructural protein 3A can mediate adaptation of foot-and-mouth disease virus to the guinea pig.

The genetic changes selected during the adaptation of a clonal population of foot-and-mouth disease virus (FMDV) to the guinea pig have been analyzed. FMDV clone C-S8c1 was adapted to the guinea pig by serial passage in the animals until secondary lesions were observed. Analysis of the virus directly recovered from the lesions developed by the animals revealed the selection of variants with two amino acid substitutions in nonstructural proteins, I(248)-->T in 2C and Q(44)-->R in 3A. On further passages, an additional mutation, L(147)-->P, was selected in an important antigenic site located in the G-H loop of capsid protein VP1. The amino acid substitution Q(44)-->R in 3A, either alone or in combination with the replacement I(248)-->T in 2C, was sufficient to give FMDV the ability to produce lesions. This was shown by using infectious transcripts which generated chimeric viruses with the relevant amino acid substitutions. Clinical symptoms produced by the artificial chimeras were similar to those produced by the naturally adapted virus. These results obtained with FMDV imply that one or very few replacements in nonstructural viral proteins, which should be within reach of the mutant spectra of replicating viral quasispecies, may result in adaptation of a virus to a new animal host.

Adaptation, Physiological↗