Viral dynamics and immune responses to foot-and-mouth disease virus in African buffalo (Syncerus caffer).

Foot-and-mouth disease (FMD) is one of the most important livestock diseases restricting international trade. While it is clear that African buffalo (Syncerus caffer) act as the main wildlife reservoir, viral and immune response dynamics during FMD virus acute infection have not been described before in this species. We used experimental needle inoculation and contact infections with three Southern African Territories serotypes to assess clinical, virological and immunological dynamics for thirty days post infection. Clinical FMD in the needle inoculated buffaloes was mild and characterised by pyrexia. Despite the absence of generalised vesicles, all contact animals were readily infected with their respective serotypes within the first 2-9 days after being mixed with needle challenged buffaloes. Irrespective of the route of infection or serotype there were positive associations between the viral loads in blood and the induction of host innate pro-inflammatory cytokines and acute phase proteins. Viral loads in blood and tonsils were tightly correlated during the acute phase of the infection, however, viraemia significantly declined after a peak at 4 days post infection (dpi), which correlated with the presence of detectable neutralising antibodies. In contrast, infectious virus was isolated in the tonsils until the last sampling point (30 dpi) in most animals. The pattern of virus detection in serum and tonsil swabs was similar for all three serotypes in the direct challenged and contact challenged animals. We have demonstrated for the first time, that African buffalo are indeed systemically affected by FMD virus and clinical FMD in buffalo is characterized by a transient pyrexia. Despite the lack of FMD lesions, infection of African buffalo was characterised by high viral loads in blood and oropharynx, rapid and strong host innate and adaptive immune responses and high transmissibility.

Emergency FMD Serotype O Vaccines Protect Cattle against Heterologous Challenge with a Variant Foot-and-Mouth Disease Virus from the O/ME-SA/Ind2001 Lineage

Vaccination is one of the best approaches to control and eradicate foot-and-mouth disease (FMD). To achieve this goal, vaccines with inactivated FMD virus antigen in suitable adjuvants are being used in addition to other control measures. However, only a limited number of vaccine strains are commercially available, which often have a restricted spectrum of activity against the different FMD virus strains in circulation. As a result, when new strains emerge, it is important to measure the efficacy of the current vaccine strains against these new variants. This is important for countries where FMD is endemic but also for countries that hold an FMD vaccine bank, to ensure they are prepared for emergency vaccination. The emergence and spread of the O/ME-SA/Ind-2001 lineage of viruses posed a serious threat to countries with OIE-endorsed FMD control plans who had not reported FMD for many years. In vitro vaccine-matching results showed a poor match (r1-value < 0.3) with the more widely used vaccine strain O1 Manisa and less protection in a challenge test. This paper describes the use of the O3039 vaccine strain as an alternative, either alone or in combination with the O1 Manisa vaccine strain with virulent challenge by a O/ME-SA/Ind-2001d sub-lineage virus from Algeria (O/ALG/3/2014). The experiment included challenge at 7 days post-vaccination (to study protection and emergency use) and 21 days post-vaccination (as in standard potency studies). The results indicated that the O3039 vaccine strain alone, as well as the combination with O1 Manisa, is effective against this strain of the O/ME-SA/Ind/2001d lineage, offering protection from clinical disease even after 7 days post-vaccination with a reduction in viraemia and virus excretion.

Antibody Response of Buffalo Calves to Different Levels of Foot and Mouth Disease Virus Immunogen

Antibody response of buffalo calves to different levels of Foot and Mouth Disease (FMD) virus immunogen was investigated. Vaccine containing 106.2 units of immunogen/TCID50 of FMD virus (O, A and Asia-1) serotypes induced log2 (1.3± 0.4) units of anti-FMD O Complement Fixing Geometric Mean antibody (FMD O CFT-CGM) titer, log2 (1.4±0.3) units of anti-FMD A CFT-CGM titer and log2 (2.0±0.7) units of anti-FMD Asia-1 CFT-CGM titer. The vaccine containing 2x106.2 units of immunogen of each of the virus serotypes induced log2 (2.2±0.2) units of anti- FMD O CFT-CGM titer, log2 (2.1±0.25) units of anti- FMD A CFT-CGM titer and log2 (3.4±0.8) units of anti-FMD Asia-1 CFT-CGM titer. The vaccine containing 3x106.2 units of TCID50 of each of the virus serotypes induced log2 (5.3 ± 2.0) units of anti-FMD O CFT-CGM titer, log2 (4.6±1.9) units of anti-FMD A CFT-CGM titer and log2 (5.0±2.2) units of anti- FMD Asia-1 CFT-CGM titer. Moreover, buffalo calves (n=3) which were primed and boosted with 60 days interval using vaccine containing 2x106.2 units of immunogen of each of the virus serotype, showed log25.0 and log26.3 units of anti FMD O CFT-GMT antibody titer, log24.6 and log26.0 units of anti FMD A CFT GMT antibody titer, log25.6 and log26.0 units of anti FMD Asia-1 CFT GMT antibody titer, on 30 and 120 days post boosting. Antibody response of buffalo calves was directly proportional to amount of FMD virus immunogen serotypes in the vaccine.

Sero-epidemiology of Foot-and-Mouth Disease in Darfur area, Western Sudan

A total of 367 bovine sera positive to antibodies against non-structural proteins (NSPs) of foot-and-mouth disease (FMD) virus were screened for serotype O, A and SAT2 antibodies using the virus neutralization test (VNT). Sera had been collected in 2016 from North (228) and South (139) Darfur States in Western Sudan, where high and low circulation of FMD virus, respectively, prevailed. Tested sera represented the positive-NSPs lot in a random sample of 669 sera collected from both States. According to standard statistical methods, calculations for serial testing (NSPs ELISA and VNT) were applied to estimate prevalence rates of serotype specific antibodies in the two States. In each State, around 20% of NSPs positive sera failed typing. Prevalence's detected were 49%±5% (O), 27%±5% (A) and 14%±4% (SAT2) in North Darfur State and 27%±5% (O), 17%±4% (A) and 8.0%±3% (SAT2) in South Darfur State. In both States, prevalence rates were significantly higher for serotype O, followed by A then SAT2; the same order that was known in most parts of Sudan. Consistently, estimated prevalence's were statistically significantly higher (P < 0.05) in North Darfur than in South Darfur State. Apart from serotype SAT2, detected prevalence rates were lower or similar to those inside the country in previous occasions. Frequency and pattern of distribution of serotype O prevalence were consistent with its suggested pattern of circulation from the Nile valley to other parts in Sudan and significant within the country's circulation. Alternatively, serotype SAT2 prevalence and distribution in Darfur area were suggestive of sporadic occurrence. However, slightly higher prevalence rates of SAT2 antibodies in Darfur than in neighbouring Kordofan areas in 2013 reflected the wide dissemination of SAT2 (http://www.wrlfmd.org) in Sudan in early 2014. Risk of FMD in Darfur seemed to be associated with the movement of animals to the North in the wet season as part of the pastoral system, and with movement related to trade into urban centers more than with pastoralism across the Western borders. Generally, the result presented little evidence to suggest presence of FMD primary endemic foci in Darfur area.

Production of a Foot-and-Mouth Disease Vaccine Antigen Using Suspension-Adapted BHK-21 Cells in a Bioreactor

The baby hamster kidney-21 (BHK-21) cell line is a continuous cell line used to propagate foot-and-mouth disease (FMD) virus for vaccine manufacturing. BHK-21 cells are anchorage-dependent, although suspension cultures would enable rapid growth in bioreactors, large-scale virus propagation, and cost-effective vaccine production with serum-free medium. Here, we report the successful adaptation of adherent BHK-21 cells to growth in suspension to a viable cell density of 7.65 × 106 cells/mL on day 3 in serum-free culture medium. The suspension-adapted BHK-21 cells showed lower adhesion to five types of extracellular matrix proteins than adherent BHK-21 cells, which contributed to the suspension culture. In addition, a chemically defined medium (selected by screening various prototype media) led to increased FMD virus production yields in the batch culture, even at a cell density of only 3.5 × 106 cells/mL. The suspension BHK-21 cell culture could be expanded to a 200 L bioreactor from a 20 mL flask, which resulted in a comparable FMD virus titer. This platform technology improved virus productivity, indicating its potential for enhancing FMD vaccine production.

Seroepidemiology of Foot and Mouth Disease using passive surveillance techniques in selected provinces of Lao PDR

Foot and Mouth Disease (FMD) is a high-impact, contagious transboundary animal disease that is endemic in Southeast Asia. Abattoir samples were routinely collected in six selected provinces between March and December 2019. A total of 1280 samples of abattoir animals were tested for FMD Non-Structural Protein (NSP) antibodies to indicate natural infections. Overall, 22.8% were seropositive for FMD NSP antibodies while seroprevalence of cattle (n = 469), buffalo (n = 214), and pigs (n = 597) were 44.6%, 35.0%, and 1.3%, respectively. The highest seroprevalence destination province was Xiengkhouang (35.3% of 272 samples), followed by Savannakhet (27.0% of 244 samples). Risk factors for evidence of natural infection identified by a multivariate logistic regression model included age groups (p-value = 0.02) and origin provinces (p-value = 2.8 × 10−5) of the animals. There were significant differences of FMD NSP seroprevalence between age groups and origin provinces of the animals. The odds ratio of a seropositive result in the less than 1 year old group was 2.5 (95% CI; 1.4, 4.4) when compared to the 3–4 years old group, while the odds ratios for animals that originated from Khammouane and Xiengkhouang provinces were 4.5 (95% CI; 1.1, 18.7) and 2.4 (95% CI; 1.4, 4.1), respectively, when compared to Champasak province. Serotype-specific antibody ELISA for 44 NSP antibody–positive samples revealed evidence of FMD serotypes O and A virus circulation in some provinces. Despite the passive abattoir survey providing useful information on FMD virus previous exposure and geographic locations of the animals, timely information on FMD virus circulation and distribution is also crucial to an effective control program. Alternative approaches to increase the cost-effectiveness of the surveillance network are also discussed.

Therapeutic and Prophylactic Potential of FMD Virus-specific Polyvalent Immunoglobulins during an FMD Outbreak in Cattle

Foot and mouth disease (FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals worldwide. In the present study the therapeutic and prophylactic potential of polyclonal, polyvalent FMD virus-specific bovine antibodies has been investigated as a possible approach for rapid control, lessening of the severity of clinical signs and prophylactic protection of susceptible animals during FMD outbreaks. The prepared FMD virus-specific polyvalent immunoglobulins were concentrated, purified, filter sterilized (0.22nm) and its titer against the FMD virus serotypes, A, O and SAT2, was adjusted to 2.15, 2.25 and 2.10 log10 TCID50/ml, respectively. In an experimental FMDV induced infection, the immunoglobulin therapy was given 4 days post experimental infection. The effect of different doses of immunoglobulins (4, 6 and 8ml) the severity of the clinical signs, healing of lesions and virus shedding was determined. A dose of 8 ml (2.0 log10 TCID50/ml) of the prepared FMD virus-specific antibodies proved highly effective in reducing the severity of the clinical signs and inducing recovery within 48 - 96hrs post therapy, as compared with the control non-treated infected calves. A dose related recovery rate was recorded. Field trial was conducted and evaluated during the FMD outbreak in Egypt during 2016/2017. Significant reduction of the morbidity of the disease and 100% reduction of mortality were recorded. The prepared FMD virus-specific bovine polyvalent antibodies proved to be a drug of choice during FMD outbreaks protecting susceptible animals and inducing rapid recovery of diseased one associated with reducing clinical signs severity and reducing virus shedding.

The role of meat and meat products in the spread of foot and mouth disease

The analysis of the results of epizootic investigations carried out in the foci of foot and mouth disease and data from the study of the role of meat, meat products, meat processing waste and non-neutralized kitchen waste in the spread of the foot and mouth disease virus in a number of European countries (England, Belgium, Greece, Italy, Germany and Switzerland), the Soviet Union (Kyrgyz SSR, Latvian SSR, Magadan, Sakhalin, Leningrad and Kamchatka regions), Russian Federation (1995). Outbreaks of foot and mouth disease in Mongolia in February - March were caused by the transport of susceptible animals infected with foot and mouth disease virus and their slaughter products on the eve of the religious New Year holiday [1, 10]. Recently, the Russian Federation is free from foot and mouth disease. However, cases of the introduction of the FMD virus from neighboring countries unfavorable for this infection are recorded [8]. The greatest danger is posed by meat obtained from the slaughter of animals during the incubation period, as well as from vaccinated cattle infected with the FMD virus [2830]. The article presents the results of the indication of the FMD virus in samples from different organs and tissues infected with the FMD virus of animals. Information about the modes of disinfection of meat and meat products is presented.