Induction of a protective antibody response to foot and mouth disease virus in mice following oral or parenteral immunization with alfalfa transgenic plants expressing the viral structural protein VP1.
(1/437)
The utilization of transgenic plants expressing recombinant antigens to be used in the formulation of experimental immunogens has been recently communicated. We report here the development of transgenic plants of alfalfa expressing the structural protein VP1 of foot and mouth disease virus (FMDV). The presence of the transgenes in the plants was confirmed by PCR and their specific transcription was demonstrated by RT-PCR. Mice parenterally immunized using leaf extracts or receiving in their diet freshly harvested leaves from the transgenic plants developed a virus-specific immune response. Animals immunized by either method elicited a specific antibody response to a synthetic peptide representing amino acid residues 135-160 of VP1, to the structural protein VP1, and to intact FMDV particles. Additionally, the immunized mice were protected against experimental challenge with the virus. We believe this is the first report demonstrating the induction of a protective systemic antibody response in animals fed transgenic plants expressing a viral antigen. These results support the feasibility of producing edible vaccines in transgenic forage plants, such as alfalfa, commonly used in the diet of domestic animals even for those antigens for which a systemic immune response is required. (+info)
Demonstration of bovine CD8+ T-cell responses to foot-and-mouth disease virus.
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The aim of this study was to investigate the importance of cellular immunity in foot-and-mouth disease in cattle, in particular to determine whether a CD8+ T-cell response could be detected, as these cells may play a role in both immunity and virus persistence. As attempts to characterize classical cytotoxic T cells had yielded non-reproducible results, largely due to high backgrounds in control cultures, a proliferation assay was developed that was demonstrated to detect antigen-specific, MHC class I-restricted bovine CD8+ cells responding to foot-and-mouth disease virus (FMDV). Proliferative CD8+ T-cell responses were detected consistently from 10 to 14 days following infection with FMDV and typically lasted 3-4 weeks. The role of CD8+ T cells in control of the disease, in particular their relevance for the establishment of persistence, may now be investigated. (+info)
Evidence of partial protection against foot-and-mouth disease in cattle immunized with a recombinant adenovirus vector expressing the precursor polypeptide (P1) of foot-and-mouth disease virus capsid proteins.
(3/437)
A recombinant live vector vaccine was produced by insertion of cDNA encoding the structural proteins (P1) of foot-and-mouth disease virus (FMDV) into a replication-competent human adenovirus type 5 vaccine strain (Ad5 wt). Groups of cattle (n = 3) were immunized twice, by the subcutaneous and/or intranasal routes, with either the Ad5 wt vaccine or with the recombinant FMDV Ad5-P1 vaccine. All animals were challenged by intranasal instillation of FMDV 4 weeks after the second immunizations. In the absence of a detectable antibody response to FMDV, significant protection against viral challenge was seen in all of the animals immunized twice by the subcutaneous route with the recombinant vaccine. The observed partial protection against clinical disease was not associated with a reduction in titre of persistent FMDV infections in the oropharynx of challenged cattle. (+info)
Genetic analysis of type O viruses responsible for epidemics of foot-and-mouth disease in North Africa.
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The nucleotide sequences of the 3' end of the capsid-coding region were determined for 30 serotype O foot-and-mouth disease (FMD) viruses isolated between 1987 and 1994 from outbreaks in North Africa and the Middle East. These sequences were compared with the previously published sequences of 9 field virus isolates from the Middle East and 5 vaccine virus strains, 3 of which originated from the Middle East (O1/Turkey/Manisa/69, O1/Sharquia/Egypt/72 and O1/Israel/2/85) and 2 from Europe (O1/Lausanne/Switzerland/65 and O2/Brescia/Italy/47). Cluster analysis of these sequences using the unweighted pair group mean average (UPGMA) method showed: (i) that the FMD viruses isolated from North Africa and the Middle East were very different from the classical European vaccine strains; (ii) that all the viruses isolated during the 1989-92 North African epidemic formed a cluster differing by no more than 6% from each other; (iii) a virus isolated in Libya in 1988 was unrelated to the aforementioned epidemic; and (iv) viruses from a second, less extensive epidemic, occurring in 1994, fell into yet another cluster. (+info)
Predicting the level of herd infection for outbreaks of foot-and-mouth disease in vaccinated herds.
(5/437)
Foot-and-mouth disease (FMD) is a highly contagious virus infection of sheep, goats, cattle, pigs and other, non-domesticated species of artiodactyls, and causes both clinical and subclinical infection according to the natural or acquired immunity of the host. Within vaccinated dairy herds FMD may appear as an acute, mild or subclinical infection, dependent upon the immune status of the herd, the level of challenge and the efficacy of the vaccine used. In the large dairy herds of Saudi Arabia, sub-clinical FMD was on a number of occasions, found to have spread amongst the cattle before signs of disease were seen. Such undetected transmission resulted in a large incidence on the first day of diagnosis and curtailed the impact of post-outbreak vaccination (PoV). First day incidence (FDI) for these herds was found to correlate with the final cumulative incidence of clinical disease. Since FDI is available at the start of an outbreak it can be used as a predictive tool for the eventual outcome of an FMD outbreak. During the past 11 years 47 % of dairy herds examined in Saudi Arabia have experienced FMD initially as sub-clinical disease. For the remaining 53 %, waning vaccinal protection did not suppress clinical disease in the initially infected animals, and these showed severe rather than mild signs. Hence, in such herds there was a very low initial level of subclinical infection, so PoV was more effective, and the timing of PoV was found to give a good correlation with cumulative herd incidence: an early PoV resulted in low prevalence of clinically infected animals whilst late PoV permitted high prevalence. PoV timing can thereby be used in tandem with FDI as a predictive tool for future outbreaks, estimating the final cumulative incidence (or prevalence) of clinical FMD cases. (+info)
Development of replication-defective adenovirus serotype 5 containing the capsid and 3C protease coding regions of foot-and-mouth disease virus as a vaccine candidate.
(6/437)
A recombinant replication-defective human adenovirus serotype 5 vector containing FMDV capsid, P1-2A, and viral 3C protease coding regions was constructed. Two viral clones were isolated, Ad5-P12X3CWT, containing the wild-type (WT) 3C protease that processes capsid polyprotein precursor into mature capsid proteins, and Ad5-P12X3CMUT, containing a point mutation in the protease coding region that inhibits processing. In 293 cells infected with either virus, synthesis of the FMDV capsid polyprotein precursor occurred, but processing of the polyprotein into structural proteins VP0, VP3, and VP1 occurred only in 3CWT virus-infected cells. Immunoprecipitation with monospecific and monoclonal antibodies indicates possible higher order structure formation in Ad5-P12X3CWT virus-infected cells. The viruses were used to elicit immune responses in mice inoculated intramuscularly (im). Only virus containing the 3CWT elicited a neutralizing antibody response. After boosting, this neutralizing antibody response increased. Swine inoculated im with Ad5-P12X3CWT virus developed a neutralizing antibody response and were either completely or partially protected from contact challenge with an animal directly inoculated with virulent FMDV. This adenovirus vector may be an efficient system for the delivery of FMDV cDNA into animals, leading to a high level of neutralizing antibody production and protection from FMDV challenge. (+info)
Protection of mice against challenge with foot and mouth disease virus (FMDV) by immunization with foliar extracts from plants infected with recombinant tobacco mosaic virus expressing the FMDV structural protein VP1.
(7/437)
A tobacco mosaic virus (TMV)-based vector has been used to express in plants the complete open reading frame coding for VP1, the major immunogenic protein of foot and mouth disease virus (FMDV). In vitro RNA transcripts were inoculated into Nicotiana benthamiana plants and detectable amounts of recombinant VP1 were identified by Western blot as soon as 4 days postinfection. Foliar extracts prepared from infected leaves were injected intraperitoneally into mice and all of the immunized animals developed a specific antibody response to both the complete virus particle and the major immunogenic region as determined by ELISA and Western blot analysis. Most importantly, all immunized mice developed a protective immune response against experimental challenge with virulent FMDV. To our knowledge, this is the first report showing the expression of a complete open reading frame of an antigenic foreign protein in plants, using a recombinant plant virus, in sufficient quantity to permit use of the crude plant extract as an experimental immunogen to protect animals against virus challenge. (+info)
The evaluation of hypersensitivity tests in cattle after foot-and-mouth disease vaccination.
(8/437)
The response to passive cutaneous anaphylaxis, dermal hypersensitivity and intravenous provocation tests has been compared in 30, 40, 31 and 24 cattle injected with foot-and-mouth disease vaccine 0, 1, 2 and 3 times respectively, using vaccine components and other substances as test materials. Reaginic antibodies demonstrated by passive cutaneous anaphylaxis in goats, were directed against BHK 21 cell extracts (20), hydroxypropylmethylcellulose (3) and an unidentified vaccine component (3), and distributed in 0, 5, 19 and 75 per cent of the cattle vaccinated 0, 1, 2 and 3 times. None of the animals showed clinical signs of allergy after vaccination. When BHK 21 cell extract was injected intradermally a significant correlation was noted between the development of large weals and the presence of reagins although the size of the weals was not correlated with the reagin titres. In the case of hydroxypropylmethylcellulose a similar trend was evident. The majority of cattle with large dermal weals possessed reagins but the number of reactions was too small for statistical evaluation. Dermal reactions to sodium penicillin, sodium carboxymethylcellulose, saponin and whole vaccine occurred in both unvaccinated and vaccinated cattle but BHK 21 cell lysate and normal bovine serum provoked weals which increased in frequency according to the number of vaccinations experienced. Intravenous hydroxypropylmethylcellulose elicited a response in all the animals previously injected with certain batches of vaccine but cell extract intravenously produced a clinical response in half the tested animals which was uncorrelated with the results of the passive cutaneous anaphylaxis or dermal hypersensitivity tests. (+info)