Foot-and-mouth disease. Challenge of cattle after multiple vaccinations

Four groups of six cattle were vaccinated from two to five times at 6 month intervals with two different trivalent FMD vaccines licensed in the given year. The FMDV type A strains in the vaccines designated A5F and A5B were closely related. Three months after the last vaccination the cattle were challenged by contact with animals inoculated with the original field strain A5B. The inoculated animals developed typical FMD symptoms with vesicles in the mouth and on the feet. Those cattle which had received vaccines that did not contain strain A5B also became severely sick, even after five vaccinations. Animals vaccinated twice with type B containing vaccine were also not completely protected. A safe protection can obviously only be achieved for fairly short periods of time if vaccine and challenge strain are homologous. It is proposed to change the rules of licensing, to speed up the procedure to vaccinate in cases of outbreaks. The need for further research, especially into improving vaccines, is stressed.     

Endurance of immunity against foot-and-mouth disease in cattle after three consecutive annual vaccinations

Protection against foot-and-mouth disease (FMD) and ability to transmit FMD virus to susceptible contact animals were studied in cattle vaccinated three times in annual field campaigns with the Dutch trivalent vaccine. Eighty vaccinated cattle and 16 susceptible controls were intranasally exposed to an aerosol containing a homologous FMD challenge virus (O1 BFS, A10 Holland or C1 Detmold) or a heterologous virus (A5 Modena or C1 Modena). The day after exposure, vaccinated cattle were stabled individually with an FMD-susceptible contact. All cattle challenged with an homologous virus strain at one year (20 head), at two years (10 head) and at three years (30 head) after the last vaccination were protected against the development of clinical signs of disease; one, zero and five cattle of these groups, respectively, transmitted virus to their contacts. In each group, approximately two out of three exposed cattle had virus-positive oropharyngeal fluid samples and seroconverted. The amount of virus recovered from probang samples increased with the time since the last vaccination. Mean antibody titres of cattle that had not been vaccinated for three consecutive years did not change significantly over the last two-year period. All 10 cattle challenged with the vaccine strain-related C1 Modena virus were protected against clinical disease, whereas three out of 10 challenged with the heterologous A5 Modena strain virus one year after the last vaccination contracted FMD and transmitted the virus. Five others (four in the C1 group and one in the A5 group) spread the virus to their contacts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of different adjuvants for foot-and-mouth disease vaccine containing all the SAT serotypes

Foot-and-mouth disease (FMD) is an economically important disease of cloven-hoofed animals that is primarily controlled by vaccination of susceptible animals and movement restrictions for animals and animal-derived products in South Africa. Vaccination using aluminium hydroxide gel-saponin (AS) adjuvanted vaccines containing the South African Territories (SAT) serotypes has been shown to be effective both in ensuring that disease does not spread from the endemic to the free zone and in controlling outbreaks in the free zone. Various vaccine formulations containing antigens derived from the SAT serotypes were tested in cattle that were challenged 1 year later. Both the AS and ISA 206B vaccines adjuvanted with saponin protected cattle against virulent virus challenge. The oil-based ISA 206B-adjuvanted vaccine with and without stimulators was evaluated in a field trial and both elicited antibody responses that lasted for 1 year. Furthermore, the ISA 206 adjuvanted FMD vaccine protected groups of cattle against homologous virus challenge at very low payloads, while pigs vaccinated with an emergency ISA 206B-based FMD vaccine containing the SAT 1 vaccine strains were protected against the heterologous SAT 1 outbreak strain.     

Transmission of foot-and-mouth disease by vaccinated cattle following natural challenge

Cattle vaccinated with a conventional monovalent type O1 foot-and-mouth disease (FMD) vaccine were challenged between four and 21 days after vaccination by short-term exposure to homologous airborne virus produced by pigs. Transmission was then assessed by housing susceptible cattle with the vaccinated animals and testing and observing all the animals for signs of infection and clinical disease. All 18 cattle vaccinated three weeks before challenge resisted clinical disease and although four contracted subclinical infection, there was no transmission to susceptible cattle in contact. One of the two groups of cattle vaccinated two weeks previously transmitted subclinical infection, but not disease, to susceptible animals housed with them from day 0 after challenge. Subclinical infection was manifested by a transient viraemia which was not followed by a detectable circulating antibody response. Shorter periods (seven or four days) from vaccination to challenge resulted in transmission of disease from clinically normal vaccinated to in-contact animals in one of two experiments. The severe challenge presented by the diseased in-contact animals than overwhelmed the immunity of the vaccinated animals. The results indicate that during emergency vaccination programmes it is advisable to vaccinate all FMD-susceptible animals within the vaccination zone and that at the outer boundary of the zone vaccinated animals should be kept separated from unvaccinated animals for at least three weeks.     

Detection of foot-and-mouth disease virus infection in vaccinated cattle

The aim of this study was to evaluate the value of commercially available kits for the detection of foot-and-mouth disease (FMD) virus infection in vaccinated cattle. The cattle were vaccinated with a commercial aqueous FMD vaccine type A24 and subsequently challenged 28 days post vaccination with homologous FMD virus. Seven of eight animals were protected from clinical disease and all became carriers. They were bled sequentially for up to 130 days post infection and samples of sera were tested with three ELISA kits: CHEKIT FMD-3ABC, Ceditest FMDV-NS and SVANOIR FMDV 3ABC-Ab ELISA. The Ceditest kit appears to be relatively higher sensitive than the others. When examined with this ELISA, all cattle developed of FMDV nonstructural proteins (NSPs) antibodies and remained positive throughout the period of the experiment. The response of antibodies against 3ABC antigen delayed in two cattle challenged with FMDV A24 virus. One of the cattle reacted negatively in Svanoir ELISA kit and sera from two animals were found negative in CHEKIT ELISA. It can be concluded that all tested kits can be a promising tool for FMD control and eradication campaigns in situation where emergency vaccination was applied.     

Effectiveness of vaccines and vaccination programs for the control of foot-and-mouth disease in Uganda, 2001–2010

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. In Uganda, FMD outbreaks are mainly controlled by ring vaccination and restriction of animal movements. Vaccination stimulates immunity and prevents animals from developing clinical signs which include lameness, inappetence, and decreased production. Ring vaccination and restriction of animal movements have, however, not successfully controlled FMD in Uganda and outbreaks reoccur annually. The objective of this study was to review the use of FMD virus (FMDV) vaccines and assess the effectiveness of vaccination programs for controlling FMD in Uganda (2001–2010), using retrospective data. FMD vaccine distribution patterns in Uganda (2001–2010) matched occurrence of outbreaks with districts reporting the highest number of outbreaks also receiving the largest quantity of vaccines. This was possibly due to “fire brigade” response of vaccinating animals after outbreaks have been reported. On average, only 10.3 % of cattle within districts that reported outbreaks during the study period were vaccinated. The average minimum time between onset of outbreaks and vaccination was 7.5 weeks, while the annual cost of FMDV vaccines used ranged from US $58,000 to 1,088,820. Between 2001 and 2010, serotyping of FMD virus was done in only 9/121 FMD outbreaks, and there is no evidence that vaccine matching or vaccine potency tests have been done in Uganda. The probability of FMDV vaccine and outbreak mismatch, the delayed response to outbreaks through vaccination, and the high costs associated with importation of FMDV vaccines could be reduced if virus serotyping and subtyping as well as vaccine matching were regularly done, and the results were considered for vaccine manufacture.     

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.     

Developments in diagnostic techniques for differentiating infection from vaccination in foot-and-mouth disease

Foot-and-mouth disease (FMD) is a highly contagious and economically significant disease of cattle, pigs, sheep, goats and wild ruminant species. The FMD virus genome encodes a unique polyprotein from which the different viral polypeptides are cleaved by viral proteases, including eight different non-structural proteins (NSPs). Both structural and non-structural antigens induce the production of antibodies in infected animals. In contrast, vaccinated animals which have not been exposed to replicating virus will develop antibodies only to the viral antigens in the inactivated material. Vaccination against FMD is a key element in the control of the disease in addition to slaughter and movement restrictions. However, countries that vaccinate in the event of an outbreak will have to re-establish their FMD free status to the satisfaction of their trading partners.Because currently available vaccines stimulate the production of antibodies indistinguishable from those produced by infected animals in response to live virus and because vaccinated animals can be infected and become carriers of FMD virus, efforts have been made to develop diagnostic test that can differentiate vaccinated animals from those that are convalescent and from those that have been vaccinated and become carriers following subsequent contact with live virus. Currently the detection of antibodies to non-structural protein's (NSPs) is the preferred diagnostic method to distinguish virus infected, carrier, animals from vaccinated animals. However this is currently only possible at the herd level because of the great variability in the initiation, specificity and duration of the immune response in individual animals to the NSPs shown in many studies. Considerable effort and attention is now being directed toward the development of new methods and techniques for the rapid and accurate detection of anti-NSP antibodies, harmonization and standardization of current diagnostic techniques, as well as the production of defined reagents.     

Cedivac-FMD can be used according to a marker vaccine principle

In this study, we investigated whether Cedivac-FMD, an emergency vaccine against foot-and-mouth disease (FMD), is suitable for use conjointly with a screening program intended to confirm freedom from disease in vaccinated herds based on evidence of virus replication in vaccinates. Different sets of sera were tested using the Ceditest FMDV-NS ELISA for the detection of antibodies against non-structural proteins (NSPs) of FMD virus. During a vaccine safety study, serum samples were collected from 10 calves, 10 lambs and 10 piglets following administration of a double dose and a repeat dose of high payload trivalent Cedivac-FMD vaccine. All serum samples collected both 2 weeks following the administration of a double dose as well as those collected 2 weeks after the single dose booster (given 2 weeks after the double dose) were negative in the Ceditest FMDV-NS ELISA. In a series of vaccine potency experiments, serum samples were collected from 70 vaccinated cattle prior to and following exposure to infectious, homologous FMD virus. When testing cattle sera collected 4 weeks after vaccination with a regular dose of monovalent >6 PD(50) vaccines, 1 of 70 animals tested positive in the NSP antibody ELISA. After infection with FMD virus, antibodies to NSP were detected in 59 of 70 vaccinated cattle and 27 of 28 non-vaccinated control animals within 7 days. Cedivac-FMD vaccines do not induce NSP antibodies in cattle, pigs or sheep following administration of a double dose or a repeat dose. FMD-exposed animals can be detected in a vaccinated group within 7-14 days. Because Cedivac-FMD does not induce NSP antibodies, the principle of 'marker vaccine' applies.     

Response of Bali cattle (Bos javanicus) to vaccination with Brucella abortus strain 19 in West Timor

A trial was conducted in two villages (one containing cattle infected with brucellosis and one not containing infected cattle) in Timor, Indonesia to determine the serological response to vaccination with Brucella abortus strain 19 in Bali cattle (Bos javanicus) (n = 599). Mature female cattle were immunised with low-dose strain 19 (2x10(8)-6x10(8) colony forming units) and calves (6-12 months) with high-dose strain 19 (4x10(10)-12x10(10) colony forming units). Other mature females and calves were inoculated with sterile vaccine diluent and formed a non-vaccinated in-contact control group. The seroprevalence and mean titres were highest in the vaccinated cattle 3 months after vaccination. These then receded, however, 1% of vaccinated calves and 1.9% of vaccinated cows from the village without infected cattle were still seropositive on the complement-fixation test (CFT) 24 months after vaccination. Non-vaccinated seropositive animals were more likely to have aborted or had a stillbirth and were less likely to have produced a calf than were seronegative cows from the village containing infected animals. We concluded that strain 19 vaccine induced protection in Bali cattle and that this vaccine might play an important role in the control of bovine brucellosis in Timor.     

The effectiveness of foot-and-mouth disease vaccines in Switzerland. II. Stability problems

One of the vaccines that were used in 1988 to immunize the Swiss national cattle population against foot-and mouth disease (FMD) was apparently not stable. Data, provided by the manufacturer, indicated a high initial antigenic content for serotype O. Protection experiments at the end of the vaccination campaign, however, indicated a substantial loss of serotype O antigen in the vaccine. Serological data, obtained during the campaign indicated that only 12% of the primovaccinated animals and 63% of previously vaccinated animals received an amount of FMD viral antigen sufficient to induce protective immunity. The primovaccinated animals were revaccinated in fall 1988 with a new batch provided by the same manufacturer. The new vaccine induced high titers of neutralizing antibodies in primo- and an anamnestic response in revaccinated cattle.     

Association of the time that elapsed from last vaccination with protective effectiveness against foot-and-mouth disease in small ruminants

Routine and emergency vaccination of small ruminants against foot-and-mouth disease (FMD) is mandatory in many endemic countries, yet data on the field effectiveness of the vaccines used is scarce. We conducted an investigation of a serotype O FMD outbreak that took place in a sheep and goat pen, and estimated the effectiveness of various routine vaccination statuses. We also evaluated the protection provided by colostrum administration and emergency vaccination. Animals which were routinely vaccinated twice were not clinically affected while disease incidence was observed among animals routinely vaccinated only once (p = 0.004 according to a two-sided Fisher''s exact test). In groups vaccinated only once, there was a significant association between the average time that elapsed since last vaccination and the disease incidence (n = 5; Spearman correlation coefficient: r_s = 1.0, p < 0.01). In addition, non-vaccinated lambs fed colostrum from dams vaccinated more than 2 months before parturition had a mortality rate of 33%. Administration of emergency vaccination 2 days after the occurrence of the index case was the probable reason for the rapid blocking of the FMD spread within 6 days from its onset in the pen.     

The effects of Brucella strain 19 vaccination on titers in the tube agglutination test: a case control study.

The degree of agglutination in the tube agglutination test of the sera of 373 "reactor" cattle was compared to that of 800 "non-reactor" cattle from multiple reactor herds in southwestern Ontario. Vaccinated cattle had lower titers than did nonvaccinated cattle. Thus, vaccinated cattle were less likely to be classified as positive than nonvaccinated cattle irrespective of the method of interpreting the results of the tube test. When the full allowance for vaccination was used, vaccinated cattle were less likely to be classified as suspicious than nonvaccinated cattle. The extent of herd vaccination did not appear to markedly influence the effects of vaccination or the prevalence of reactors. Thus, it appeared that vaccination with strain 19 produced a small protective effect (inferred from the lower titers in vaccinated animals), but that the magnitude of this effect was markedly dependent on the appropriateness of the vaccine allowance for classifying cattle. Further work is needed on this aspect of vaccination with strain 19.     

The foot-and-mouth disease epidemic in The Netherlands in 2001

An outbreak of foot-and-mouth disease (FMD) in Great Britain was reported on 21 February 2001, followed by an outbreak of FMD in The Netherlands a month later. This Dutch index outbreak occurred on a mixed, veal-calf/dairy-goat farm in Oene, in the central part of The Netherlands. The most-likely route of infection was the import of Irish veal-calves to this Dutch herd via an FMD-contaminated staging point in France. With hindsight, more herds seemed to be infected by the time the index outbreak was confirmed. The regular EU control measures were implemented, in combination with pre-emptive culling of herds within 1km of each outbreak. Nevertheless, more outbreaks of FMD occurred. Most of the virus infections on those farms were "neighborhood infections". Because the situation seemed out of control locally and the destruction capacity became insufficient, it was decided to implement an emergency vaccination strategy for all biungulates in a large area around Oene to stop further spread of the virus. All susceptible animals on approximately 1800 farms in this area were vaccinated. All farms subsequently were depopulated, starting from 2 weeks after vaccination. In total, 26 outbreaks were detected (the last outbreak on 22 April 2001). In total, approximately 260,000 animals were killed.     

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.     

Prevalence of seroreagents to FMDV in the cattle population in Poland: results of 9-year monitoring studies

The aim of this study was to evaluate the occurrence of antibodies to foot-and-mouth disease virus (FMDV) in sera of cattle in Poland. The examinations were performed using the virus neutralization (VN) test and ELISA methods: liquid-phase blocking ELISA (LPBE) and 3ABC-ELISA. During 1993-2001, about 681,000 samples of sera collected from animals held on the territory of Poland were tested. Of about 600,000 sera taken from animals exported to the European Union, 963 samples (0.16%) were found to be positive to FMDV types A, O and/or C. During 1996-2001 out of 85,000 sera tested as part of the national serological surveillance program for FMD, the FMDV antibodies were recorded in 51 (0.06%) samples. Persistence of FMD antibodies was observed in sera of cattle from the region around Zduńska Wola, which had been vaccinated annually during 1985-1985 with trivalent FMD vaccine. The results of the serological studies of 550 animals from this region indicates the presence of FMDV antibodies in sera of 240 (44%) cattle. A half-life of maternal antibodies in sera of calves born to seropositive dams was estimated; the highest level of FMDV antibodies was detected in sera taken from new-born calves aged 5-10 days. The level of FMDV antibodies in beestings of dams was highest during the first 10 hours after parturition; after 24 hours a significant decrease (3-5 times) was found and in two weeks post parturition FMDV antibodies were undetectable in the milk. It was established that all LPBE/VN positive sera of cattle exported from Poland, from the vaccination zone around Zduńska Wola as well as those tested as part of the national serological surveillance program for FMD, were taken exclusively from vaccinated animals or calves born to vaccinated dams.     

A complex-trapping-blocking (CTB) ELISA, using monoclonal antibodies and detecting specifically antibodies directed against foot-and-mouth disease types A, O and C. II. Application

The complex-trapping-blocking (CTB) enzyme-linked immunosorbent assay (ELISA) was evaluated to detect antibodies directed against foot-and-mouth disease virus (FMDV) strains A10 Holland, O1 BFS, and C1 Detmold. Log10 serum titres of uninfected, unvaccinated cattle (n = 100) were less than 1.80 in the CTB-ELISA. Sera from cattle vaccinated with either monovalent or trivalent vaccines were tested in both the CTB-ELISA and the serum neutralisation test (SNT); titres in both tests correlated positively (P less than 0.001). Titres of sera from cattle, sheep, and pigs vaccinated twice with FMDV A10 Holland also correlated positively in both tests. In another experiment, cattle vaccinated with FMDV strain C1 Detmold were intradermolingually challenged 3 weeks after primary vaccination; at the same time two controls were challenged. At 8 days after challenge, serum titres of the controls were distinctly higher in the CTB-ELISA than in the SNT, whereas serum titres of the vaccinated cattle were equally high in both tests. In potency tests for monovalent vaccines against FMDV strains A10 Holland, O1 BFS or C1 Detmold, serum titres correlated strongly in both tests with protection against the homologous FMDV strain. We concluded that the CTB-ELISA is not only sensitive, but easier to perform and more rapid and reproducible than the SNT. The CTB-ELISA may be useful in evaluating the immune response in cattle during FMD vaccine potency tests.     

Characteristics of foot and mouth disease virus in Taiwan

Since March 1997 two strains of foot and mouth disease (FMD) virus have found their way into Taiwan, causing severe outbreaks in pigs and in Chinese yellow cattle. Outbreaks occurred in March 1997 were caused by a pig-adapted virus strain (O/Taiwan/97) which did not infect other species of cloven-hoofed animals by natural route. The epidemic spread over the whole region of Taiwan within two months and the aftermath was 6,147 pig farms infected and 3,850,746 pigs destroyed. In June 1999, the second strain of FMD virus (O/Taiwan/99) was isolated from the Chinese yellow cattle in the Kinmen Prefecture and in the western part of Taiwan. By the end of 1999, Chinese yellow cattle were the only species infected and those infected cattle did not develop pathological lesions. Seroconversions of serum neutralization antibody and on non-structural protein (NSP) antibodies were the best indicators for infection in non-vaccinated herds. The infected animals, however, excreted infectious levels of virus to infect new hosts. Based on the detection of the specific antibody to FMD virus, and virus isolation from oesophageal-pharyngeal (OP) fluid samples, ten herds of Chinese yellow cattle located in Kinmen and Taiwan were declared to have been infected. During the period of January to March 2000, however, five outbreaks caused by FMD virus similar to the O/Taiwan/99 virus occurred in four prefectures of Taiwan. The infected species included goats, Chinese yellow cattle and dairy cattle. Those outbreaks have caused high mortality in goat kids under two weeks old and also developed typical clinical signs of infection in dairy cattle.     

Dose-response evaluation of a genetically engineered foot-and-mouth disease virus polypeptide immunogen in cattle

Four groups of 9 cattle each were vaccinated with 10, 50, 250, or 1,250 micrograms of foot-and-mouth disease (FMD) virus A12 VP1 fusion protein that was produced in Escherichia coli and emulsified in an oil adjuvant. The groups given the 10 and 50 micrograms of antigen were revaccinated at 15 weeks and were challenge exposed at 30 weeks; 5 of 9 and 7 of 9 cattle, respectively, were protected from FMD virus infection. The remaining 2 groups, vaccinated with 250 or 1,250 micrograms of antigen, were revaccinated at 32 weeks and were challenge exposed at 45 weeks; 8 of 9 and 9 of 9 cattle, respectively, were protected. The results indicated that the biosynthetic polypeptide FMD vaccine was effective using vaccination intervals frequently followed with conventional whole-virus vaccines.     

Field trial of a quadrivalent vaccine against calf respiratory disease

A quadrivalent vaccine containing the killed antigens of respiratory syncytial virus, parainfluenza virus type 3, Mycoplasma dispar and M bovis, emulsified with an oil adjuvant, was tested for efficacy against naturally occurring calf respiratory disease. Three batches of beef cattle aged 12, seven and three weeks at the time of first vaccination were used. Within each batch of approximately 100 animals, half were vaccinated subcutaneously on three occasions, three weeks apart and half served as unvaccinated controls. Over the trial period, from November 1981 to May 1982, 27 per cent of the control calves were treated for respiratory disease compared with 16.3 per cent of the vaccinated animals. This reduction of non-fatal disease in the vaccinated animals represented a protection rate of almost 40 per cent and was statistically significant (P less than 0.05). Mortality was also reduced from 3.4 per cent in the control calves to 1.9 per cent in the vaccinated animals but this difference was not statistically significant. During a major outbreak of disease associated with respiratory syncytial virus, the protection rate increased to 69 per cent (P less than 0.01). Furthermore, in the batch of cattle aged seven weeks at first vaccination there was significantly less pneumonic consolidation at death in the vaccinated animals than in the control animals (P less than 0.05).