CHALLENGES IN FMDV STRAIN SELECTION AS AN INPUT TO ATTAIN BROAD VACCINE CROSS-PROTECTION

PEDEMONTE, A; MARADEI E; BERGMANN I.E.; GALDO NOVO, S.; MALIRAT V

Bangkok

Encuentro; 2019 GFRA: Global Foot-and-Mouth Disease Research Alliance. SCIENTFIC MEETING; 2019

Global Foot-and-Mouth Disease Research Alliance

Vaccination against foot and mouth disease virus (FMDV) is regarded as the most effective way to prevent infection. Selection of appropriate vaccine strains is rather challenging due to lack of cross protection between serotypes and incomplete protection between some strains within a serotype. Furthermore, effectiveness of a vaccine in the field can be affected by vaccine formulation and vaccination approaches, among others.Continuous monitoring of vaccine protection against circulating and emerging strains is a key input for decision making policies regarding maintenance and/or update of suitable vaccine strains and vaccination strategies. In this context, a successful outcome will strongly depend on a multifaceted approach comprising several actors that must work together effectively, including epidemiologists, field veterinarians, laboratory experts, vaccine producers and veterinary authorities. An ideal vaccine strain should be as immunogenic and cross reactive as possible. However, a strain that does not completely comply with these requirements can be effective considering that other determinants play an important role in the protection outcome, such as potency, (high potency vs. regular vaccines), booster doses of the vaccine and the effect of additional serotypes and strains. This has been demonstrated through field experience for some historical strains with proven protection against circulating viruses. Estimation of FMDV antigen cross protection is quite challenging, not only because of the multiple scenarios which need to be contemplated (different vaccine formulations, revaccination schemes, various objectives for application, etc.), but also because at present no in vitro test is available to reliably associate the cross-reactivity with cross-protection. This correlation may depend on the characteristics inherent to the vaccine strain, which by mechanisms not well understood can confer a good protection, even with low cross-reactivity. Moreover additional contributions of the vaccine/vaccination characteristics also need to be regarded. Taking into account the above, an approach including a test algorithm is recommended and the final evaluation must perform the gold standard test, which is the in vivo cross protection approach. This in vivo approach has many disadvantages from the standpoint of animal welfare and biosafety. Furthermore it is expensive, the number of challenge viruses that can be assessed is limited and results can only be obtained after more than a month. Here, the long-term existing South American vaccine strains O1 Campos and A24 Cruzeiro, with proven efficacy for a broad vaccine cross-protection, were assessed against currently viruses circulating in South East Asia. Challenge results are included.Taken together with previous studies, these results allow to identify, discuss, and, where possible, offer suggestions for dealing with the challenges arising when evaluating FMDV vaccine efficacy, such as different outcomes of interest against which vaccine efficacy is estimated, study designs used to assess vaccine efficacy, sources of bias and confounding, repeat vaccination, waning immunity, population level effects of vaccination, and vaccine cross-protection in at-risk populations.