The Vaccine Differentiation Group carries out applied research that will help to control foot-and-mouth disease (FMD) and Peste des petits ruminants (PPR). The focus within the group is the development and validation of marker vaccines and associated diagnostics for both diseases. In particular we work on vaccines and companion tests that would differentiate infected from vaccinated animals (DIVA). It is possible that vaccinated animals can subsequently become infected with FMD virus. Although these animals would be protected against the clinical disease, the virus would replicate in them sub-clinically and be present persistently for a long time, posing a risk for disease spread to other susceptible animals. In addition the group is working towards PPR eradication by improving the understanding of epidemiology of PPR, early pathogenesis and developing DIVA vaccines.
Having such validated marker vaccines and associated diagnostic tests (DIVA) would enable animals to be effectively vaccinated without precluding the possibility of detecting vaccinated animals that had subsequently become infected. We have four lines of investigation:
- improving our understanding of what aspects of the immune response are important in protection of vaccinated animals against acute and persistent infection
- developing alternative means of detecting infection in vaccinated animals
- developing and evaluating improved marker vaccines (DIVA vaccines) for FMD and PPR
- Improving understanding of epidemiology and early pathogenesis of PPR
Following the UK epidemic of FMD in 2001 there has been a growing desire to develop vaccination policies for FMD that would reduce reliance on large scale slaughtering of animals. However, vaccinated animals may sometimes become infected without showing signs of disease and pose a risk of starting new outbreaks later on if the virus persists in these animals. Therefore, we are developing more effective vaccines that are needed to better block virus establishment and that do not induce antibodies against some of the immunogenic viral proteins produced during a wild-type infection that help to differentiate infection in vaccinated animals (marker vaccine and DIVA tests).
Our work has shown that the present conventional vaccines are effective in terms of clinical protection, but do not give sterile immunity. Also the vaccines have deficiencies in speed of onset and duration of protection. To strengthen the immune response to vaccination, we are involved in investigating the efficacy of conventional, inactivated FMD vaccines with addition of new generation adjuvants. We are also developing viral vectored FMD vaccines to elicit better cell mediated and mucosal immunity. These viral vectors (Sendai virus, adenovirus and vaccinia virus) expressing FMD empty capsids are being evaluated as intranasal as well as parenteral vaccines to raise specific humoral and local mucosal and cell mediated immunity on the surface of the oro-nasal mucosa to prevent the entry of FMD virus by its usual route.
Since 2010 the Vaccine Differentiation Group is working towards PPR eradication by improving the understanding of epidemiology of PPR, early pathogenesis and developing DIVA vaccines.
In diagnostics, the group is developing and validating tests that differentiate infection from vaccination for both PPR and FMD including a test for FMD-specific IgA in saliva/nasal fluid, and alternative format NSP tests (e.g. multiplexed NS assay) that detect antibodies against non-structural FMDV proteins; such antibodies are indicative of infection, as they are not produced in response to vaccination with killed FMD vaccines or vectored vaccines. The presence of high levels of IgA in the saliva of vaccinated infected cattle indicates the oro-pharyngeal replication of virus.
For supporting PPR control and eradication programme of OIE and FAO, our group is involved in developing and evaluating live attenuated DIVA vaccines and DIVA tests using reverse genetics technique and carrying out epidemiological investigations using new generation sequencing and phylogenetic analysis. Marker vaccines allow differentiation between infected and vaccinated subjects, which is particularly important for the control of disease epidemics affecting livestock. Establishment of a reverse genetics system for PPR virus using reverse genetics technique is one major achievement of this group. Development of whole blood CD4+ assay for the measurement of IFN-γ in response to FMDV antigen and salivary IgA assay for the detection of FMD carrier animals are another two major achievements for FMD. In addition the group has validated several FMD NSP and SP assays which are used in world wise for evaluation of vaccine as well as outbreak surveillance and commercialise by ID Vet, France.