INFORMES DE LA DIRECCIÓN DE EDUCACIÓN SUPERIOR

Vaccine banks (also known as antigenic banks or strategic reserves) store a variety of FMDV serotypes and strains, which can be used if an outbreak occurs. Banks may contain either ready-to-use vaccines or vaccine antigens that will be formulated, if needed, into complete vaccines. The earliest FMD vaccine banks stockpiled fully formulated, inactivated vaccines; however, these vaccines have a relatively short shelf-life and must be discarded periodically, making such banks expensive [152;201]. Currently, they usually store concentrated antigens, which are kept at ultra-low temperatures. FMD vaccine banks could also be used to stockpile other types of vaccines, such as hAd5-vectored constructs, in a ready-to- use form.

Non-commercial FMD vaccine banks are maintained in some individual countries, either in national institutes or by commercial vaccine producers. There are also two multinational cooperative banks: the North American Vaccine Bank (NAFMDVB) at the PIADC for the United States, Canada and Mexico, and the European Union Vaccine Bank (EUVB), which stores antigens in France and Italy for the E.U. These banks were uncommonly used in the past, but activation has become somewhat more frequent in recent years [109;201]. As of 2015, the NAFMDVB has never been activated. The first activation of the EUVB was for an outbreak in the Balkans in 1996 [109]. The EUVB also supplied vaccines to Japan (which did not use the vaccine) and the Republic of Korea in 2000, to Turkey in 2000 and 2006, and to Iraq in 2009 [109;152;201;221]. The International Vaccine Bank (IVB) (disbanded in 2003) was located in the UK. It was unusual in having its own independent, non-commercial facility to formulate vaccines; other vaccine banks may have contracts with manufacturers to formulate any vaccines needed [201]. The IVB had only one large-scale activation, for the 2001 epizootic in the U.K., and the vaccine was not used [109]. Some vaccine banks in individual countries are relatively active. The Argentinean FMD Vaccine

and Antigen Bank provided more than 187 million doses of vaccine between October 2000 and May 2002, to help control an epizootic in Argentina [222]. It also supplied vaccine to Uruguay [201]. A new regional FMD antigen bank, which would contain strains exotic to the region and could coordinate with the NAFMDVB, has been recommended for South and Central America [8].

Vaccine banks can store only a limited number of serotypes and strains of FMDV. Vaccine strains held in banks are generally those which are felt to have the greatest risk of introduction, based on the worldwide epidemiological situation [1]. These stocks are under continual review; important new strains are added periodically, and some stored antigens become obsolete. Strain selection is complex. The OIE/Food and Agriculture Organization (FAO) World Reference Laboratory periodically recommends and prioritizes FMDV vaccine strains for banking in FMD-free areas (in addition to separate regional recommendations for vaccines in endemic areas) [8;109]. A number of factors play a role in these recommendations, including the strains causing recent FMD outbreaks, the ability of vaccines to protect animals from other strains within that serotype, and the availability of vaccine strains within the portfolios of manufacturers that can fulfill the quality requirements for use in FMD-free regions [8]. More vaccine strains may be recommended for some serotypes than others. Serotype O is genetically diverse, but antigenically restricted, and animals can be protected from most currently circulating viruses with a small number of vaccine strains [8;223]. Serotype A and SAT viruses are genetically and antigenically diverse, and multiple vaccine strains are needed for immunization as they must closely match the outbreak strain [8;22;223]. Serotype Asia-1 has tended to be antigenically homogeneous, and only one strain was recommended for immunization and vaccine banking as recently as 2013 [8;223]. However, new Asia-1 variants that are poorly matched with the Asia-1 Shamir vaccine strain have been recognized during recent outbreaks, and additional (or other) strains may be recommended for banking in the future [8]. One vaccine strain is also recommended for serotype C, which has not been reported since 2004 [8].

FMDV antigen concentrates can be stored in vaccine banks for many years [16;152;217]. The integrity of the antigens must be maintained while they are frozen, stored, thawed and diluted [152]. During storage, some virus particles rupture or aggregate [152]. There is little information on this phenomenon, partly because the data are proprietary and are not readily published by manufacturers; however, it is considered to be normal by manufacturers if, with highly purified antigens, 10% of the initial virus particles are lost within the first five years of storage [152]. After 14 years, as much as 40% of the antigen mass may be lost in some cases [152]. The stability of FMDV antigens seems to be strain- dependent [152]. The OIE recommends testing samples for the integrity of the antigens or acceptable potency of the final product at appropriate intervals, currently recommended to be every 5 years [16]. Some tests that may be used include 146S quantification, vaccination serology or challenge studies.

In an outbreak, stored antigens from banks can be formulated rapidly into complete vaccines. These vaccines can be tailored to the epidemiology of the outbreak [109;152]. Banks are usually able to make either monovalent or polyvalent vaccines that contain oil or aluminum hydroxide/ saponin as the

adjuvant. It is possible to adjust the potency of the vaccine according to need and to the relatedness of the field and vaccine strains. The time between receipt of the order and vaccine delivery has been estimated to be 4 to 13 days, depending on the distance the antigens and/or vaccine must be shipped, the daily finishing and filling capacity of the manufacturer, and the availability of flights [152]. At an international conference for representatives of vaccine banks, manufacturers’ estimates for vaccine formulation were 3- 7 days, with the period between ordering and application in the field likely to be at least 6-10 days [223]. Noncommercial vaccine banks usually operate on a relatively small scale, and a bank may be able only to meet the initial needs during an outbreak [109]. The number of vaccine doses available should be

expressed in relation to the expected potency; it will vary with the amount of antigen per dose in the final vaccine. Because some stocks are duplicated in different banks, it might be possible to obtain additional vaccine supplies from other countries [1;109]. Cooperative agreements or formal reciprocal supply

agreements with other banks would facilitate such planning. However, vaccine banks must also consider whether to hold antigens in reserve for their own member countries if an outbreak were to spread [109]. In 2006, representatives of FMD vaccine banks approved the creation of an international FMD vaccine bank network, to operate under the auspices of the OIE [221;223]. Some of the goals of the network include addressing sudden increases in the demand for vaccine and establishing a global vaccine reserve for FMD, as well as harmonizing vaccine and test standardization and certification.