Extract
two Merial vaccines for FMD are licensed for use in the UK. For these vaccines to be used, agreement from the EU must be gained, followed by a change of UK legislation to permit their use.

(The EEC acknowledges that the current epidemic in the UK is unlike any in Europe in the last 10 years. We are on our own and can propose to the EEC how we intend to manage it. The UK government can decide to vaccinate at any moment. No agreement from the NFU is necessary)
(verbatim from the Merial website)

MERIAL'S FOOT AND MOUTH DISEASE VACCINES

THE FACTS

The current outbreak of FMD in the United Kingdom is focusing attention on the role that vaccination could play in assisting the elimination of the disease. These fact sheets detail the technical issues surrounding the vaccine. They do not cover the issue of vaccination per se, as any decision to vaccinate will be based on veterinary, political, and economic decisions taken on National and European levels. Merial, the world's leading animal health company is an expert in vaccine manufacture and has a long history in the development of vaccines against FMD and its role in the debate on the merits of vaccination is solely confined to the provision of technical advice surrounding the vaccine.

Who is Merial?


The World's leading animal health care company, Merial maintains its position through continuous innovation and the launch of relevant new products for production and companion animals. The Merial product range includes pharmaceuticals and vaccines to meet the needs of three groups of animals: livestock, companion animals (pets) and wildlife. Annually Merial continues to introduce its hugely successful portfolio of products into markets around the world to help producers, veterinarians and pet owners enhance the health, well-being and performance of all animals. In 2000 alone, countries such as Australia, Bolivia, El Salvador, Italy, Japan and South Africa benefited from the introduction of products for cats, dogs, cattle, poultry, sheep and pigs. Each of Merial's therapeutic products has been developed to meet a specific health need - whether this is for parasites, foot and mouth disease, flea and tick control, the treatment of equine ulcers, or protecting household pets against deadly heartworm disease. And the search for solutions and cures is ongoing. With its commitment to research and development, Merial continues to invest considerable resources into vaccines which effect production in farm livestock and diseases of companion animals. As these products come to market they will benefit the lives of millions of animals - and their owners - world-wide.

Merial's track record in vaccine production and Foot and Mouth Disease Merial has been producing Foot and Mouth Disease vaccines for over half a century. It owns FMD vaccine production plants at Pirbright in the UK and Paulinia in Brazil, and works closely with the U.K's Ministry of Agriculture Fisheries and Food and other governments advising on disease prevention and the application of vaccine to protect against various strains of the disease. During that time it has provided millions of doses of vaccine to national governments and international organisations for use in the event of disease outbreaks. Vaccines are used all over the world as part of integrated disease control policies for FMD. These vaccines, like all vaccines, are primarily employed in preventative strategies. They have also formed an indispensable part of several successful eradication programmes, for example, continental Europe before the cessation of vaccination in the early 1990s and Uruguay before the cessation of vaccination in 1993. Vaccine is recognised as a key part of disease management by those countries in which an eradication policy is difficult or impossible to realise for socio-economic or other reasons

The Foot and Mouth Disease virus - Background Information Foot and Mouth

disease is an acute infectious viral disease causing fever, followed by the development of vesicles (blisters) chiefly in the mouth and on the feet. It is probably more infectious than any other disease affecting animals or man and spreads rapidly if uncontrolled. It affects cattle, sheep, pigs, and goats. Wild and domestic cloven-hooved animals are also susceptible, including a significant number of zoo animals and animals such as the hedgehog. The virus responsible for the current UK outbreak of FMD is known as Pan Asian O and is closely related to the Merial vaccine strain O1 Manisa.

The vaccines - what they are

Merial's FMD vaccines are based on a suspension of highly purified inactivated antigens of the FMD virus in an adjuvant base. Because there are seven serotypes and a large number of significant variants within some of the serotypes, Merial has a substantial library of vaccine strains to provide cover against new outbreak viruses as they occur. Thus Merial was in a position within a few days of the first case in the UK to confirm that several of its vaccine strains, including O Manisa, were appropriate to protect against the disease. Depending on the epidemiological situation, FMD vaccines may contain one or more strains and monovalent, bivalent and trivalent vaccines are commonplace where the valency refers to the numbers of serotypes in the vaccine. Vaccination is either by the subcutaneous route for aqueous vaccines for cattle, sheep and goats or the intramuscular route for oil adjuvanted products for these species plus pigs. No oral vaccines are available. Merial vaccines are licensed in the UK for use in cattle, pigs, sheep and goats and while not licensed for use in zoo animals would be expected to confer immunity.

Their efficacy

It is a common perception that FMD vaccines are unable to confer high quality, lasting immunity. This is untrue as evidenced by the European vaccination campaigns before 1990 when annual vaccination was the common policy following the establishment of immunity in young animals. Like all vaccines, their efficacy - or efficiency - at generating immunity to disease depends on several factors, for example: species vaccinated physiological state, such as pregnancy or lactation degree of maternal immunity the current health status of the animals, the disease challenge from naturally occurring pathogens, the animal's stress levels at treatment the vaccine's manufacturing standards, such as dose level of antigen, purity, adjuvant and virus strain used the storage conditions of the vaccine prior to use their administration route the level of skill of their administration, in terms of dose rate and technique and, particularly, the establishment of herd immunity by vaccination of the majority of livestock within a population.

What the vaccines will do:

Merial's FMD vaccines will provide the most effective immunity when administered to quiet, disease free animals that are in good health and relatively free from other disease challenges. When used in these circumstances, a high level of disease immunity is provided in all classes of stock. To be fully effective, any vaccination policy for any disease must be used in conjunction with an integrated control strategy to minimise the degree of viral challenge and the spread of the disease.

What the vaccines will not do:

The vaccines will not necessarily provide immunity to animals that have already been in contact with the virus, even if the animals are showing no symptoms. This means that the question of previous contact with infected livestock or their surroundings must be taken into consideration when considering any vaccination programme and vaccination teams need to exercise extreme care when moving between premises where there is the possibility of subclinical disease on some of those premises. Merial vaccines are prepared from 'killed' virus and the chemical inactivation conditions used (aziridines such as binary ethyleneimine or BEI) comply fully with European Union regulatory requirements. This ensures that there is no danger that using the vaccine can cause or spread the disease. Claims to the contrary are usually founded on a period, many years ago, when other less effective inactivants such as formaldehyde were commonly used.

Administration regime and recommendations

For maximum efficacy, Merial advises that the following recommendations and regime are adopted when using the vaccine: Adopt standard zoosanitary precautions to minimise the chances of contact between animals and virus Vaccinate only clean, dry, healthy, tranquil animals that are free of FMD symptoms Animals in low risk areas should receive two vaccinations four to five weeks apart, with a booster every six months. Those in heavily infected areas should also be initially vaccinated twice over the same four to five week period, but should receive the first booster four months later. Identify and record all animal treatments. (The specific vaccination regime will also be influenced by the requirements of the National Regulatory Authorities). In ideal vaccination conditions, immunity in cattle and sheep can develop as early as four days post vaccination but it may take longer in pigs.

Use of the vaccine during a FMD outbreak

Ideally a vaccination campaign during an outbreak should begin in populations known to be uninfected. The campaign should then extend in such a manner that animals which may be incubating the disease are vaccinated last. The recommended vaccination course depends on the animals to be covered, the level of maternal antibody cover, and the degree of risk of exposure to the virus.

There is no veterinary need to slaughter vaccinated animals.

Any requirement for vaccinated animals to be slaughtered is based on economical and political factors, and in particular the desire of a given country to return to an internationally recognised FMD disease-free status. This is largely because there is evidence to show that cattle which were incubating the disease at the time of vaccination or were subsequently challenged, but showed no symptoms, may become 'carriers' of the virus. This so-called carrier state is distinct from the short term mechanical carrying of disease and may last for several years in some cattle. The fact that it is possible to isolate infectious virus from 'carrier' animals raises very major concerns for all Veterinary Authorities because of the potential for an apparently healthy animal to transmit the disease to susceptible livestock. Sheep and goats also can become carrier animals but the duration of the state is of the order of 6 to 9 months. Pigs do not become carrier animals. Vaccinated animals that have not been exposed to live virus cannot become carriers. Although there are a number of serological tests which show considerable promise in discriminating between animals which have only received vaccine and those which have been exposed to FMD virus (including vaccinated animals), none of these tests are prescribed by the Office International des Epizooties (OIE) and are therefore not recognised in terms of International Trade. The only tests fully accepted by OIE are those used to diagnose the disease and measure antibody responses to the virus or vaccine.

Vaccine and Food safety

It is considered safe to consume milk and meat products from animals infected with FMD. Infected animals in an outbreak are slaughtered and disposed of to help prevent the spread of disease and not because of any risk of passing the infection to man. Similarly, there is no danger from consuming meat or milk from vaccinated animals. Milk from these animals can be drunk immediately, and no time period between treatment and selling the milk is necessary.

What is the current status of the vaccine in the UK?

The use of vaccines to prevent FMD is not permitted in any European Union member state. In the event of a disease outbreak the EU adopts an eradication slaughter policy. However, two Merial vaccines for FMD are licensed for use in the UK. For these vaccines to be used, agreement from the EU must be gained, followed by a change of UK legislation to permit their use. The UK has access to European Union antigen banks, where stocks of antigens are held. Useable vaccines can be manufactured from these antigens in about six days. It takes around ten weeks for antigens to be produced from raw materials. Merial to date, has been the exclusive supplier to the EU antigen bank and has already made vaccines from some of those antigens for emergency control measures on the periphery of the EU. The UK also has approximately 500,000 cattle vaccine doses of the relevant O strain of the FMD virus and this is available from a small vaccine bank at the Institute for Animal Health, Pirbright The decision on whether to vaccinate is taken by Government. Naturally, any input from Merial on that decision would relate solely to the supply of technical advice on the efficacy of the vaccines, and on their administration.

Technical Information - Modern vaccines without viral non structural proteins

During infection of animals or infection of cell cultures by viruses, two kind of proteins are synthesised : 1) the structural proteins constituting the virus particles and 2) the non-structural proteins, residues of the virus replication. Raw vaccines containing the two kind of proteins induce antibodies in the serum of injected animals which mimics the antibodies spectrum of the viral infection, directed against the two kind of proteins. Modern highly purified vaccines do not contain non-structural proteins and cannot induce antibodies against these proteins. Consequently vaccinated animals show antibodies only against the whole virus particles and not against non-structural proteins. Antibodies against non-structural proteins therefore identify contaminated animals. Merial thanks to a French process started to sell such vaccines from Lyon in 1989-90, then from Pirbright in the UK since 1997. Competitors are far behind Merial for this kind of vaccines.

FMD VACCINATION, USE & EFFECTS -

A European Perspective Progress in the control of foot and mouth disease in Europe during the last 25 years has been impressive. Programmes which limit the inadvertent importation of virus into the region, together with prophylactic vaccination campaigns, have been successful in reducing the incidence of the disease to very low levels and then to absence of outbreaks which lead to the ban of vaccination in 1992. Action by member countries has been encouraged and co-ordinated by OIE and FAO, resulting in the rapid dissemination of information on new outbreaks and collaborative measures to stop the spread of infection. International collaboration to provide vaccines and technical aid in the setting up of buffer zones, has, so far, prevented the serious incursion of exotic strains into Europe. The number of FMD outbreaks in five European countries in 1952 and 1975 show a very great improvement. The events in France will be taken as an example of what can, and has been, achieved in Europe.
Table I : Number of Outbreaks of Foot and Mouth Disease per annum in Various European Countries.
Year France Belgium Holland West Germany Italy
1952 320 016 8943 7054 54 572 28 579
1975 2 21 2 13 31

In common which much of Europe, FMD was present more or less continuously in France earlier this 20th century. It was soon realised that vaccination by itself would be insufficient and that more drastic measures to reduce the weight of infection would be necessary to complement the effect of widespread immunisation. Vaccine production was increased and compulsory vaccination of all cattle was begun in March 1960. By January 1962 both compulsory slaughter and vaccination applied to the entire country. The success of these measures can be judged from the figures given in Table II which show a significant drop in the number of outbreaks from 1961 onwards. It is worth noting that pigs were not vaccinated and from time to time figured prominently in outbreaks. This is still a problem not completely resolved. The Netherlands introduced a general vaccination policy in 1952 and a slaughter policy in 1955.

Table II : Number of Foot and Mouth Disease outbreaks in France
Year No.
1911 104 321
1937 164 116
1938 218 297
1952 320 016
1957 99 000

In France, following the start of compulsory vaccination in 1960 and the application of a slaughter policy to the whole country in 1962, there was a steady fall in outbreaks until the episode in Brittany in 1974 involving type C infection in pigs, when for the first time large-scale application of oil adjuvant vaccine (1.5 million doses) was made. The situation was rapidly under control. Compulsory vaccination as a part of federal policy was introduced in West Germany in 1965 and the trend towards control of the disease has been very significant.

Notes to Editors:

Merial is the world's leading animal health company dedicated to the research, development, manufacture and delivery of innovative pharmaceuticals and vaccines for use by veterinarians, farmers and pet owners to improve the health, well-being and performance of all animal species. The company is also market leader in the development and production of poultry breeding stock. With its worldwide headquarters in London, Merial employs around 6,500 people and operates in more than 150 countries. Total 1999 sales exceeded US$1.68 billion. Merial is jointly owned by Merck and Co. Inc. and Aventis S.A.

Merial Limited Registered in England and Wales (No. 3332751) with registered offices at Knightsbridge, London SW1X 7QT, England, and domesticated in Delaware, USA as Merial LLC