THE INTERNATIONAL VACCINE BANK FOR FOOT-AND-MOUTH DISEASE
Established in 1985 the International Vaccine Bank for Foot-and-mouth disease offers its members a dedicated facility for the storage, rapid formulation, bottling and despatch of 'emergency' FMD vaccine.
Situated at: Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Surrey GU24 ONF, England.
The International Vaccine Bank (IVB) was established in 1985 by an agreement signed by the seven original members - Australia, Finland, Ireland, New Zealand, Norway, Sweden and the United Kingdom. Malta joined the IVB as an Associate member in 1995. All member countries are free from foot-and-mouth disease (FMD) and would apply a 'stamping out' policy in the first instance for the eradication of FMD following any future outbreak. However, if an outbreak threatened to become extensive or affect particularly valuable livestock, consideration would be given to 'emergency' vaccination as an additional control measure. If vaccine were to be requested by one of the member countries, IVB staff would rapidly formulate, bottle and despatch the vaccine. It is the responsibility of the receiving country to subsequently replace the used antigen from an approved commercial source.
Since the establishment of the IVB, the bank has been maintained at the Pirbright Laboratory of the Institute for Animal Health (IAH). The IVB comprises a unique facility for the storage of all components required for high potency FMD vaccine production, combined with a UK VMD licensed manufacturing suite dedicated to the emergency manufacture of FMD vaccine. Concentrated, inactivated FMDV antigen is bought from approved commercial sources and stored over liquid nitrogen. Under such storage conditions FMDV antigen has an unlimited lifespan. 'Emergency' vaccine can be formulated for use in ruminants and pigs as aqueous or oil formulations. The selection of FMDV antigens held by the IVB is determined by the perceived risk to member countries. Advice upon this and other technical matters is given to the IVB by a Technical Advisory Group which comprises world experts on FMD.
Facts and Figures
Each FMDV antigen batch held by the IVB has a nominal size of 500,000 cattle doses following reconstitution. The manufacturing facility can produce and bottle 175,000 cattle doses of aqueous vaccine in a 24 hour period under GMP (Good Manufacturing Practice) conditions. As of 1996 the FMD antigens held by the IVB include three type A strains, two type O strains, one Asia 1 strain and one type C strain. Vaccines formulated by the IVB are highly potent, which enhances early and broad spectrum protection. The acceptance criteria for all antigens is that they should produce a vaccine with a minimum PD50 value of 10 upon reformulation. The relationships of the antigens stored by the IVB to emergent field strains is continuously monitored through close links with the FAO/OIE World Reference Laboratory for FMD, which is also sited at the Pirbright Laboratory of the IAH.
The executive body of the IVB is the Commission, which meets annually and comprises the Chief Veterinary Officers (CVO's) of member countries. The Commission is chaired by the UK CVO and is empowered to take decisions relating to the activities of the IVB. According to the agreement between the member countries, the administering authority of the IVB is the UK Ministry of Agriculture, Fisheries and Food (MAFF) acting in the capacity of the Secretariat. Scientific staff of IAH, Pirbright Laboratory manage the IVB on a day-to-day basis, the Director of the IVB is the Head of Pirbright Laboratory.
Emergency vaccination can play an important supporting role in the control of outbreaks of foot-and-mouth disease (FMD) in disease-free countries. The storage of conventional formulated FMD vaccines in a strategic reserve for such eventualities is an expensive practice because the vaccine must be replaced every 18 months due to its limited shelf-life. An alternative to this costly practice is the well-established indefinite storage of concentrated, inactivated FMDV antigen at ultralow temperatures over liquid nitrogen which can be formulated rapidly into vaccine when required. Utilising this approach a seven-nation bank for FMD vaccine was established at the initiation of the United Kingdom in 1985. This concept is not unique to the IVB, notably Denmark has held reserves of FMD antigens over liquid nitrogen for many years and as early as 1980 the USA established an antigen reserve to which Canada and Mexico later subscribed. The recent establishment of a third international FMD antigen reserve for the European Community and other examples of individual countries establishing their own FMD reserves underline the increasing popularity of this approach. However, the IVB is unique in that it also houses its own dedicated manufacturing facility for the emergency formulation of FMD vaccine, which can be despatched within days of receiving a request. The IVB is located within easy reach of London's Heathrow and Gatwick Airports.
Description of Facilities
The IVB is situated within the security cordon of the Pirbright Laboratory of the BBSRC Institute for Animal Health in Surrey, England. The facility comprises two single storey buildings. One building is dedicated to the storage of bottles, packing materials and frozen oil adjuvant, whilst the other houses a +40C cold room for the storage of alhydrogel adjuvant, a liquid nitrogen storage facility for the antigen concentrates, and a manufacturing plant which consists of three blending vessels and positive pressure sterile suites that allow the preparation and bottling of approximately 175,000 bovine doses of vaccine within a 24 hour period. The facility operates according to the principles of Good Manufacturing Practice and currently holds licences from the Department of Health and the Veterinary Medicines Directorate (VMD) of the United Kingdom for the production of FMD vaccines adjuvanted with alhydrogel and saponin. The IVB has recently upgraded its facility by installing 2 x 500 litre capacity stainless steel vessels, filtration equipment and a low shear propeller mixer for the formulation of oil emulsified vaccines. To fulfil the manufacturing license obligations and maintain the IVB in a state of readiness, a routine of regular checks and maintenance work has been established which is undertaken by Bank staff on both the equipment and reagents.
Concentrated, inactivated FMD antigens are only obtained from commercial sources that offer the highest standards in vaccine manufacture and quality control. Supply of the antigens in a highly concentrated form offers the advantage of reduced storage volume. The IVB uses 330 litre liquid nitrogen refrigerators, each of which can hold 2-3 million bovine doses of antigen. The other advantages of this approach are :
a) The antigens have an almost indefinite 'shelf-life' at ultra-low temperatures, ensuring vaccine of the highest quality possible when needed.
b) The antigens can be formulated in the most suitable adjuvant for field application i.e.) oil adjuvant for pigs, aqueous vaccine for ruminants.
c) The antigens can be regularly monitored and tested for quality.
The IVB currently holds 500,000 bovine doses of A15 Thailand, A22 Iraq, A24 Cruzeiro, Asia 1 India, C1 Oberbayern, O1 Lausanne and O1 Manisa. Chosen on epidemiological grounds, the antigens reflect the field strains most likely to threaten any individual member country and have been accepted into the Bank following the demonstration of their high potency (greater than 10 PD50) in cattle when formulated with A1(OH)3 and saponin. All of the antigens held by the IVB produce vaccines of extremely high potency ( see Table 1). High potency vaccines are essential where the primary aim of the emergency programme is to prevent the amplification of an heterogeneous field strain of FMDV in a susceptible population as soon as possible after vaccination. In this respect, we have reported on the rate of development of protection in cattle following vaccination with some of these emergency vaccines and shown protection against natural infection by pig challenge at 4 days after immunization using our standard formulation and as early as 2 days post immunization using an oil adiuvanted preparation.
All of the stored antigens are tested annually for stability and efficacy by in vivo and in vitro methods including guinea pig potency tests, SDG centrifugation and SDS-PAGE analysis. The antigens are therefore unique in respect of the number of quality control tests they have undergone. This allows a high degree of confidence in both their stability and potency. In addition, the efficacy of these strains with regard to the ever changing epidemiological situation is monitored serologically and, where necessary, by in vivo methods.