Commercialization of a Synthetic, Live-attenuated FMDV Vaccine

Foot and mouth disease is distributed world-wide in over 100 countries, and has proven to be devastating to livestock of cloven-hoofed animals such as cattle, goats, sheep, pigs, and buffaloes. Similar to other members of the Picornaviridae family, there is considerable natural genetic variation in the FMDV population found in nature. There are seven serotypes of the foot and mouth disease virus, and many antigenically variable viral sub-types. The serotypes are not evenly distributed throughout the world, necessitating different vaccine cocktails for each region (Doel 2003; Li et al, 2012). From endemic transmission, approximately 24 million cattle are affected each year and over 3 million pigs are affected by FMD every year throughout the world. Outbreaks in FMD-free countries, of which there were 10 in 2011 and 2012, cost approximately $1.5 billion each year (Knight-Jones, 2013). This represents a huge market potential. FMDV-free countries seek to maintain stockpiles of vaccine to protect from a potential outbreak. There are many countries seeking to regain FMDV-free status that would be interested in an effective new FMDV vaccine.The current FMDV vaccine is an inactivated virus formulation combined with an adjuvant to improve immunity. It requires an expensive manufacturing process in a high biosafety containment facility and confers only temporary immunity in vaccinated animals. Because in part of the inefficacy of vaccines produced using conventional technology, countries sometimes elect to control outbreaks without the use of vaccination programs. The current inactivated vaccine uses technology dating back to 1937 that has not been significantly refined since the 1970s. The current vaccine also has a short shelf life and requires continuous cold storage, contraindicating its use in developing tropical countries where FMDV is a severe problem (Rodriguez and Grubman, 2009).Codagenix Inc. core technology is based on rational, computer-aided gene design, and is termed Synthetic Attenuated Virus Engineering (SAVE). SAVE generates live-attenuated viruses that are 100% antigenically identical to wildtype virus (Mueller et al., 2009). SAVE was developed in the poliovirus (Mueller et al. 2006) (Coleman et al., 2008), validated for live attenuated Influenza A vaccine candidates (Mueller et al., 2010), and shown to yield an Influenza A vaccine capable of an ultra-low, cross-protective vaccinating dose in mice (Yang et al., 2013). Our approach would use a highly attenuated live virus, which could require less production because of greater efficacy (Large amounts of live FMDV need to be grown to make the currentvaccine formulation). Inactivated vaccines use wild-type viruses; if the inactivation step is unsuccessful then fully virulent FMDV would be unleashed on a herd, creating a new outbreak instead of preventing one. An attenuated, stable, live vaccine does not have this risk. We have previously succeeded in making vaccines that require no adjuvant and that are efficacious with a single dose (Coleman et al, 2008; Yang et al, 2013).A successful live attenuated FMDV vaccine should fulfill a set of essential criteria. The vaccine should be rapidly effective to help halt the spread of an outbreak; this means that the vaccine should be effective at inducing immunity after single dose and preventing the shedding of infectious virus, ideally within a week as FMDV infection requires 3-5 days to become infectious (Sanson et al., 2011). Additional factors are important for broad application and distribution of a vaccine candidate; the vaccine should be effective against a spectrum of different serotypes and sub-types, it should prevent a carrier state from developing in an infected animals, and the vaccine formulation should be highly stable. For safety, the vaccine candidate should be capable of being manufactured without the use of a wild-type, virulent virus. To assist in eradication, the immunity induced by vaccination should be long