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Development of Molecular and Nuclear Technologies for the Control of Foot-and-Mouth Disease (FMD)
Closed for proposals
Project Type
Project Code
D32028CRP
1697Approved Date
Status
Start Date
Expected End Date
Completed Date
7 September 2015Description
Foot-and-mouth disease (FMD) is one of the most important livestock diseases known to man due to its high infection rate (ease of spread) and and its effect on the limitation of livestock movement and trade. An outbreak of FMD will have a devastating effect on a country’s food security with direct impact on national and international trade. The confirmatory diagnosis of FMD and its effective control through prophylactic, quarantine or slaughter-out procedures are therefore of paramount importance as it have financial and trade implications. Vaccination with inactivated FMD virus is undertaken to control FMD in endemic countries or countries at risk. Vaccines, whilst widely available but which should match (i.e. should be of homologous serotype and strain isolate) with virulent FMD viruses circulating in the region of vaccine use, are of variable quality, not from the homologous outbreak serotype/strain isolate, and are often stored under inadequate temperature conditions and therefore might be not as effective in the field as determined in animal experiments. Due to insufficient knowledge on vaccine strength and antigenic match (antigenic cartography) between vaccine strain and outbreak virus, it is often not possible to pinpoint the weakness of the vaccination strategy and to take action on this weakness.
Vaccine effectiveness can be determined by animal challenge, but this is both costly and difficult. In-vitro systems have been developed in different countries since the 1980's, but these are not standardized for international use. Many countries now produce FMD vaccines but often without effective consideration of their effectiveness. This CRP will investigate methods and possibly provide internationally acceptable guidelines for procedures which test a vaccine’s ability to induce the production of protective antibodies in cattle without the need for animal challenge experiments.
In many developing countries, vaccination will continue to be an essential component for the progressive control of FMD. Maximising the effectiveness of current vaccines and supporting research to improve the effectiveness and quality of those and or new vaccines will be critical. Countries using locally produced vaccines need to assure trade partners that they are using quality assured vaccines in order to overcome the restrictive effects of endemic FMD. The provision of internationally accepted guidelines for quality assurance and alternatives to the present need for animal challenge vaccine trials would be a significant step forward. It is likely that control and eventual eradication in endemic areas with a low level resource base (much of Africa, parts of Asia and Latin America) will require the use of quality assured vaccine preparations, correct vaccine formulations (i.e. homologous strain or isolate vaccine to protect against outbreak, new generation vaccines with a broader protection base (i.e. cross protection between different strains and isolates) or alternative formulations of existing vaccines.
This CRP is proposed for five years with three RCMs.
Objectives
The CRP is linked to project to reduce the impact on transboundary animal diseases (2000012). To develop, evaluate and validate methods, guidelines and protocols for the more effective quality control of FMD vaccines (ie FMD characterization and FMD vaccine matching with FMD field virus outbreaks) and their application in endemic countries as part of the FAO program for the global progressive control and eventual eradication of FMD in domesticated animal reservoirs.
Specific objectives
Establish guidelines for optimum population vaccination intervals based on in vitro measurements of potency and duration of the antibody response to structural proteins, after vaccination of cattle and small ruminants with commercially available FMD vaccines, including evaluation of reduced dose options such as intradermal administration of FMD vaccine
Establish methods and develop internationally agreed protocols for measuring, and improving, the potency of FMD vaccines
Establish protocols and guidelines for application and interpretation of vaccine matching methods (antigenic cartography) to identify the extent of expected cross-protection of FMD virus types (type A or SAT)
Overall Assessment of Progress Towards Achieving the CRP Objectives
Provide further global co-ordination of current research into FMD vaccines for use in endemic settings
Impact
CRP D32028 Control of FMD had the following impacts:
(1) More than 50 SOPs and scientific publications came from this CRP (directly or associated). Several of these SOPs and procedures are being accepted or in process of being evaluated by OIE as recommended procedures.
(2) The project involved countries and laboratories both from endemic and regions free from FMD. The participating laboratories have different levels of expertise ranging from internationally acclaimed research facilities with numerous global collaborations to laboratories that presently cannot perform diagnostic assays due to various reasons. One aspect of the CRP was to make the expertise available to those laboratories that are in need, to set up the links and build capacities to better understand FMD epidemiology and spread and vaccine matching.
(3) Greater networking and communication. Participants were strongly encouraged to contact the agreement and contract holders for research inputs and other needs.
(4) The project covered a number of aspects related to vaccines and post vaccination monitoring. The sequence comparison between FMD vaccine and FMD field virus methodology relies on using only the sequence data once a new virus emerges and to apply that sequence to the bio-informatical model developed in this project to determine whether the current vaccine strains will provide protection (or level of protection). Since sequence data can be generated rapidly once a new variant FMD virus is detected, this method could significantly shorten the period between detection and decision on vaccine strains.
(5) The Southern African serotypes (SAT1, SAT2, SAT3) are distinct to the other serotypes (Type O, Type A, Asia 1), and their protection parameters are different. More validation for SAT2 is planned for the future. Typically, a SAT2 vaccinated animal is not protected from SAT2 infection and disease. This compliments the approach in South America where they are optimizing the Virus Neutralization Test (VNT) results to predict protection against the vaccine strains used in the region. The predictions are based on previous challenge data where the antibody titres were correlated to protection against live virus challenge. Once this baseline is available, decisions regarding protection can be based on VNT titres only. However, it is important that the tests are validated to ensure the correct decisions are reached.
(6) An important outcome is the statistical evaluation of factors that impact on the variability observed with VNT data. Two laboratories that use VNTs for vaccine matching purposes participated in this effort. Early reports indicated that most of the variability cannot be linked to any known factors, but increasing the data set used for evaluation across two different laboratories may provide more information that would be applicable to all laboratories performing these assays. One laboratory has established a multiplex PCR based diagnostic assay that both confirms disease and provide information on the FMD serotype. The challenge is to ensure the test is rolled out to all labs in that country performing FMD diagnostics, and then to the rest of the FMD community.
(7) The bio-informatics model developed and evaluated in this CRP proved to be a fast and confirmatory tool in the matching of available FMD vaccines to FMD field outbreaks. For all FMD serotypes, the matched vaccines provided more than 80% protection in field trials. For SAT2 vaccine matched to field virus, a best 50% was observed in field trials. This will be further investigated. The CRP developed bio-informatics model are being considered by OIE as recommended procedure.
Relevance
The CRP contributed to the understanding of FMD epidemiology. The main achievement of the CRP was to establish evaluated criteria for the matching of FMD vaccines with associated FMD field outbreaks - i.e. to ensure that a particular FMD vaccine is the best match to provide protection against threat of that FMD serotype virus. This is critical to ensure the timely and effective response to FMD outbreaks in different countries with different animal dynamics.