Evolutionary and Ecological Drivers Shape the Emergence and Extinction of Foot-and-Mouth Disease Virus Lineages.

Livestock farming across the world is constantly threatened by the evolutionary turnover of foot-and-mouth disease virus (FMDV) strains in endemic systems, the underlying dynamics of which remain to be elucidated. Here, we map the eco-evolutionary landscape of cocirculating FMDV lineages within an important endemic virus pool encompassing Western, Central, and parts of Southern Asia, reconstructing the evolutionary history and spatial dynamics over the last 20 years that shape the current epidemiological situation. We demonstrate that new FMDV variants periodically emerge from Southern Asia, precipitating waves of virus incursions that systematically travel in a westerly direction. We evidence how metapopulation dynamics drive the emergence and extinction of spatially structured virus populations, and how transmission in different host species regulates the evolutionary space of virus serotypes. Our work provides the first integrative framework that defines coevolutionary signatures of FMDV in regional contexts to help understand the complex interplay between virus phenotypes, host characteristics, and key epidemiological determinants of transmission that drive FMDV evolution in endemic settings.

Booster administration can make a difference in the antibody response to intradermal foot-and-mouth disease vaccination in cattle.

Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals. Routine vaccination is one of the preferred methods of protection against this disease in endemic countries. For protective immunity against FMD, repeated immunizations with frequent administration are required. Intradermal immunization has many advantages over intramuscular administration of vaccines. In this study, a commercial tetravalent FMD vaccine adjuvanted with Montanide ISA 206 was administered to cattle via the intramuscular (2 mL [n = 10] and 0.5 mL [n = 9]) and intradermal (0.5 mL [n = 11]) routes. Booster doses were administered 28 days later using the same vaccine and routes. Serum samples were collected on days 0, 7, 14, and 28 post-vaccination (pv) and at 30 and 60 days post-booster. Homologous and heterologous virus neutralization tests and liquid-phase blocking and isotype ELISAs were used to measure the antibody response. The results showed that intradermal administration of quarter doses of the vaccine provides an equal or better virus neutralization antibody response than intramuscular administration of the same dose of vaccine after booster administration in cattle. This means that four times more cattle can be immunized with the same amount of vaccine using the intradermal route without compromising immunity.

Evaluation of Quil-A, E. coli DNA and Montanide™ ISA 206 adjuvant combination on the antibody response to foot-and-mouth disease vaccine in sheep.

Vaccination is one of the basic strategies in the fight against foot-and-mouth disease (FMD) in endemic regions. Today, commercially available FMD vaccines are prepared with inactive whole virion, which has low immunogenicity. Therefore, considerable effort has been devoted to finding novel adjuvants. Although mineral oils are among the most common adjuvants, it is still difficult to provide a long-term and robust immune response. Combined adjuvant systems are currently being studied to solve the problem. Saponins and CpG-ODNs have been shown to increase the immune response to vaccines individually in various studies. In this study, the effect of different adjuvants and their combinations (Quil-A, E. coli DNA, and MontanideTM ISA 206) on total and neutralizing antibody response in sheep was investigated. According to the results, the Quil-A group induced the highest antibody level, followed by the combination of Quil-A and the E. coli DNA group. The group containing E. coli DNA also caused a higher antibody response than the group containing only MontanideTM ISA 206 for certain days of sampling. These affordable alternatives of saponin and CpG sources can be used individually to increase the potency of the FMD vaccine for mass vaccinations of sheep. Keywords: foot-and-mouth disease; vaccine; adjuvant; Quil-A; E. coli DNA; combination of adjuvants.

The role of herpesviruses (BoHV-1 and BoHV-4) and pestiviruses (BVDV and BDV) in ruminant abortion cases in western Turkey.

The economic impact of abortions in ruminant breeders is one of the biggest problems in livestock. Of the infectious agents, viruses, especially herpesviruses and pestiviruses, are the most important causative agents of abortion in ruminants. In the present study, the role of herpesviruses (bovine herpesvirus-1 (BoHV-1), bovine herpesvirus-4 (BoHV-4)) and pestiviruses (bovine viral diarrhea virus (BVDV), border disease virus (BDV)) was investigated in cases of ruminant abortion between 2007 and 2015 in western Turkey. Out of 81 aborted fetal samples (60 calves, 19 lambs, and 2 kids), 42 were positive, which included 31 calves, 9 lambs, and 2 goats; 39 aborted fetal samples were negative for the pestivirus antigen ELISA. BoHV-1 antigen ELISA was positive in 3 cases which included 2 calves and 1 lamb; the remainder 78 cases were negative. Pestivirus and BoHV-1 were positive in 51.85 and 3.70 %, respectively, of the samples. According to PCR analysis, BoHV-4 was not encountered in any of the tested samples. In one of the calf fetus samples, both BVDV and BoHV-1 were positive; in one of the lamb fetus samples, BoHV-1 was positive. There was a much higher level of pestivirus antigen than the other viral agents evaluated in the study (p < 0.0001). The results of this study indicate that pestiviruses are a common viral cause of ruminant abortions in the examined area.

Implementing an Organizational Culture of Biosafety and Biosecurity in the SAP Institute.

An organizational culture of biosafety and biosecurity is critical for effective management of transboundary animal diseases. One essential aspect of this work is keeping important pathogens studied in veterinary laboratories under control. Türkiye is among the countries that are both endemic and disease-free for foot-and-mouth disease (FMD) virus, and it has a unique institute dedicated to FMD diagnosis, control, and vaccine production. To build an organizational safety culture within this institute and strengthen awareness of the importance of safe and secure handling of FMD, 4 staff members previously trained in biorisk management developed and provided trainings to all institute staff. The institute's 173 personnel were divided into 3 groups by job description based on direct or indirect work with FMD virus. All 3 groups received training that addressed biosecurity, biosafety, biorisk awareness, and insider threat; the trainings varied in length by group. Three-quarters (n=130, 75%) of all institute staff completed their training and were asked to complete knowledge surveys using a Likert scale survey before and after their training. A majority (n=104, 80%) of those participants completed both the pretraining and posttraining surveys. All 3 training groups' posttraining surveys showed improved awareness above baseline scores, and all 3 groups scores reached the targeted threshold goal. Group 2 demonstrated a realization that some of the knowledge and habits they had acquired through experience were incorrect. Scores for several individual questions decreased at posttraining, and these results will need further evaluation. The overall training results prompted the institute to provide periodic updates to employees to sustain the organizational safety culture. With this study, the institute now has a dedicated group of biorisk management representatives. This work serves as a wake-up call for established institutions that rely on staff experience to foster an organizational culture of biosafety and biosecurity.

The effects of simultaneous foot-and-mouth disease and Escherichia coli vaccination on the immunity of pregnant cows and their calves.

Fighting against infectious diseases with almost 18 million cattle spread over a wide geographical area is troublesome economically and physically. The administration of different vaccines simultaneously during the foot-and-mouth disease (FMD) vaccination campaign will help reduce both the vaccine stress of animals and the field veterinarians' workload. Diarrhea due to Escherichia coli (E. coli) is a significant problem and a major cause of mortality in calves, and thus, simultaneous application of FMD and E. coli vaccines to dams would prove efficient in field conditions. This study aimed to investigate the effect of simultaneous administration of four different locally produced gel and oil adjuvant inactivated E. coli vaccines with locally produced oil adjuvant inactivated FMD vaccine on neutralizing antibody levels and the properties of the antibodies in late-term pregnant dams and their calves. For this purpose, seven to eight-month-old pregnant dams (n = 146) were divided into two main groups to receive two doses (single and booster), or only single dose (no booster). FMD neutralizing antibody titers were evaluated by a virus neutralization test against serotype A, O, and Asia1. In addition, the properties of antibodies against serotype A were assessed by isotype and avidity ELISAs. E. coli antibodies were measured by the hemagglutination inhibition test. Results of the study revealed no safety problems in any dams after the vaccinations. On day 42, calves of the dams vaccinated simultaneously had higher neutralizing antibody titers against three serotypes than the calves of only FMD vaccinated dams. IgG1/IgG2 ratio was higher in single-dose groups than booster-dose groups against serotype A in calves. The avidity index was detected over the threshold value (24.5%). A positive correlation was found in the transmission of maternal antibodies from mothers to calves in simultaneous administration groups. In conclusion, during the FMD vaccine campaigns, FMD and E. coli vaccines can be simultaneously applied to dams in the 7th and 8th months of gestation. Results of this study has led to the inclusion of simultaneous application of FMD and E. coli vaccines in the 'Animal Disease and Animal Movement Control Program-2018' and these two vaccines have been applied in the field ever since as a solution for field veterinarians to save time and labor during vaccination.

Monitoring the performance of foot-and-mouth disease vaccines prepared against local strains in the face of antigenic evolution in the field.

National programs for foot-and-mouth disease (FMD) eradication includes the use of vaccination; Turkey which is endemic to FMD virus (FMDV) (except for the Thrace region) and there is a risk of incursion of exotic strains from eastern borders. In 2015, a devastating outbreak was caused by the A/ASIA/G-VII (G-VII) lineage, which led to the inclusion of a new vaccine strain (A/TUR/15) derived from this lineage in 3 months. Although most of the cattle population in Turkey was then immunized with A/TUR/15 (vaccine coverage: 92.8%), the G-VII lineage continued to cause outbreaks in the field despite the evidence of protection observed with A/TUR/15 in in vivo and in vitro tests. When G-VII field strains were examined, changes in their genomes were detected. As the lineage appeared to be evolving, an unconventional vaccination strategy was adapted which changed the vaccine strain with new variants of G-VII according to antigenic evolution. To assess the suitability of candidate vaccine strains derived from the variants of the G-VII lineage, three viral candidates were assessed (A/TUR/15, A/TUR/16 and A/TUR/17) by in vitro virus neutralization tests for r1 vaccine matching and in vivo heterologous challenge tests. Although all three vaccine strains were antigenically well matched with each other and other G-VII field viruses, due to continues outbreaks the vaccine strain was changed three times in 20 months from A/TUR/15 (Dec 2015) to A/TUR/16 (Dec 2016) and then to A/TUR/17 (Aug 2017). With this strategy serotype A has not been observed in the field since January 2018. This study highlights the importance of adapting the vaccine strains according to antigenic evolution as this could be a valuable combat strategy in endemic countries, rather than using well-known vaccine strain and relying only on the relationship coefficient (r1 ) value.

Effect of simultaneous administration of foot-and-mouth disease (FMD) and anthrax vaccines on antibody response to FMD in sheep.

PURPOSE: Foot-and-mouth disease (FMD) and anthrax are important diseases in sheep. Vaccination is a favorable strategy against both infections. Simultaneous administration of vaccines does generally not impede the immune responses of each other, although there are some exceptions, and it may help reduce the labor and costs of vaccination as well as distress on animals. Although oil adjuvant FMD vaccine has been tried with live anthrax vaccine in cattle, there are no reports on the simultaneous use of both vaccines in sheep. MATERIALS AND METHODS: In this study, FMD seronegative sheep were used to investigate the impact of the simultaneous vaccination of FMD and anthrax on FMD antibody titers of sheep. Virus neutralization test and liquid phase blocking enzyme-linked immunosorbent assay were used to determine the antibody response to the FMD vaccine. RESULTS: The results demonstrated that both vaccines can be used simultaneously without any interference with the FMD response. Moreover, the simultaneous administration with anthrax vaccine had a stimulating effect on the early (day 7 post-vaccination) virus neutralization antibody response to the FMD vaccine. CONCLUSION: The simultaneous use of the FMD and anthrax vaccines did not hinder the response to the FMD vaccine in sheep.