Evaluation of Potency and Duration of Immunity Elicited by a Multivalent FMD Vaccine for Use in South Africa.

South Africa (SA) experiences sporadic foot and mouth disease (FMD) outbreaks irrespective of routine prophylactic vaccinations of cattle using imported commercial vaccines. The problem could be mitigated by preparation of vaccines from local virus strains related to those circulating in the endemically infected buffalo populations in the Kruger National Park (KNP). This study demonstrates the individual number of protective doses (PD) of five vaccine candidate strains after homologous virus challenge, as well as the vaccines safety and onset of humoral immunity in naïve cattle. Furthermore, the duration of post-vaccination immunity over a 12-month period is shown, when a multivalent vaccine prepared from the five strains is administered as a primary dose with or without booster vaccinations. The five monovalent vaccines were shown to contain a 50% PD between 4 and 32, elicit humoral immunity with antibody titers ≥2.0 log10 from day 7 post-vaccination, and cause no adverse reactions. Meanwhile, the multivalent vaccine elicited antibody titers ≥2.0 log10 and clinical protection up to 12 months when one or two booster vaccinations were administered within 6 months of the primary vaccination. An insignificant difference between the application of one or two booster vaccinations was revealed. Owing to the number of PDs, we anticipate that the multivalent vaccine could be used successfully for prophylactic and emergency vaccinations without adjustment of the antigen payloads. Furthermore, a prophylactic vaccination regimen comprising primary vaccination of naïve cattle followed by two booster vaccinations 1.5 and 6 months later could potentially maintain herd immunity over a period of 12 months.

Efficacy of a foot-and-mouth disease vaccine against a heterologous SAT1 virus challenge in goats.

Goats are susceptible to infection with foot-and-mouth disease virus (FMDV), but their role in the epidemiology of the disease and response to vaccination is poorly understood. In southern Africa, FMDV serotypes Southern African Territories (SAT) 1, 2 and 3 are known to be endemic. In this study, we evaluated the efficacy of a pentavalent FMD vaccine in goats against heterologous challenge with a pool of field SAT1 FMDV. Forty FMD sero-negative goats (6-12 months of age) of mixed sexes were randomly allocated to one of five treatment groups: full cattle dose (2 ml), 1/3rd (0.67 ml), 1/6th (0.33 ml), 1/12th (0.16 ml) or unvaccinated placebo control. Goats were vaccinated with an inactivated pentavalent FMD vaccine containing serotypes SAT1, SAT2 and SAT3 on day 0 and revaccinated at day 20 post vaccination. Thereafter, thirty-four goats were challenged by tongue inoculation at day 41 post-vaccination using 104.57 50% tissue culture infective dose (TCID50) FMDV SAT1 pool. Animals were examined daily and clinical signs were scored. Rectal temperatures were measured daily, with temperatures ≥40 °C defined as fever. Clinical specimens (nasal, oral and rectal swabs) were collected on days 0, 2, 4 and 6 post challenge. Viral shedding was determined using reverse-transcriptase real-time PCR. None of the goats vaccinated with the full cattle dose developed secondary lesions. All vaccinated groups had lower temperatures compared to the unvaccinated controls (P < 0.001). Based on RT-PCR results, goats in the unvaccinated control group shed more virus compared to all groups except for 1/12th (P < 0.05), while goats in the full dose group shed less virus than goats in the 1/12th and the unvaccinated control group (P < 0.05). The results suggest that the 1/3rd (0.67 ml) dose of the vaccine is sufficient to reduce viral shedding after heterologous challenge with a FMDV SAT1 pool.

A novel method for performing antigenic vaccine matching for foot-and-mouth disease in absence of the homologous virus.

Foot-and-mouth-disease (FMD) is a highly contagious transboundary animal disease that has negative consequences on regional and international trade. Vaccination is an important approach for FMD control and an essential consideration is the degree of cross-protection conferred by the vaccine against currently circulating field viruses. The objective of this study was to evaluate a new vaccine matching technique that does not require knowledge concerning the homologous vaccine virus. As a proof of concept, the vaccine-match was assessed for 41 FMD field viruses isolated from southern Africa over a 25-year period. A diverse group of 20 SAT1 and 21 SAT2 FMDV isolates collected from cattle and wildlife during 1991-2015 were selected for this study. Virus neutralization tests were performed against two sets of pooled sera for each serotype: vaccinated cattle sera (4-16 weeks post-vaccination) and convalescent cattle sera (3 weeks post-experimental challenge). Novel r1-values were calculated as the ratio of the titre of the vaccinated sera to the titre for convalescent cattle sera. A validation r1-value was calculated based on an assumption concerning the true homologous vaccine virus. There was a strong positive correlation between r1-values for the novel and the validation methods for SAT1 viruses (Spearman's rho = 0.84, P < 0.01) and a very strong correlation for SAT2 viruses (Spearman's rho = 0.90, P < 0.01). In addition, there was moderate to good agreement between the novel and validation methods for both serotypes based on a r1-value cut-off of 0.3, which is presumed to represent a good vaccine-match. The agreement between methods using prevalence-adjusted and bias-adjusted kappa (PABAK) was 0.67 and 0.84 for SAT1 and SAT2 viruses, respectively. The new r1-value method provides a feasible, alternative vaccine matching approach that could benefit FMD control in southern Africa.

Vaccine Potential of Two Previously Uncharacterized African Swine Fever Virus Isolates from Southern Africa and Heterologous Cross Protection of an Avirulent European Isolate.

African swine fever (ASF) is a mostly fatal viral infection of domestic pigs for which there is no vaccine available. The disease is endemic to most of sub-Saharan Africa, causes severe losses and threatens food security in large parts of the continent. Naturally occurring attenuated ASF viruses have been tested as vaccine candidates, but protection was variable depending on the challenge virus. In this study, the virulence of two African isolates, one from a tick vector and the other from an indigenous pig, was determined in domestic pigs to identify a potential vaccine strain for southern Africa. Neither isolate was suitable as the tick isolate was moderately virulent and the indigenous pig virus was highly virulent. The latter was subsequently used as heterologous challenge in pigs first vaccinated with a naturally attenuated isolate previously isolated in Portugal. Although a statistically significant reduction in death rate and virus load was observed compared with unvaccinated pigs post-challenge, all pigs succumbed to infection and died.

Foot-and-mouth disease marker vaccine: cattle protection with a partial VP1 G-H loop deleted virus antigen.

Contrary to the dogma that the VP1 G-H loop is essential for FMD vaccine efficacy, it has been previously shown that foot-and-mouth disease 146s antigen containing heterologous VP1 G-H loops confers complete protection in pigs and cattle. Moreover, serological evaluation of cattle vaccinated with an antigen lacking a large proportion of the VP1 G-H loop indicated that these animals should be protected against infection with FMD. Absence of this loop provides opportunity for the development of an FMD negative marker vaccine, allowing infection to be detected by antibodies against this missing region. Cattle vaccinated with this negative marker vaccine were fully protected following virus challenge 28 days post vaccination as determined by the absence of generalised lesions on their feet. Furthermore, use of our improved differentiation ELISA identified animals exposed to infection as early as 7 days post-challenge. We thus demonstrate, for the first time, the ability of this FMD negative marker vaccine to fully protect cattle from experimental challenge and rapidly distinguish animals that are subsequently exposed to infection.