Scale-Up Production of Type O and A Foot-and-Mouth Disease Bivalent Vaccine and Its Protective Efficacy in Pigs

Abstract

South Korea has experienced FMD outbreaks almost every year since 2014. Therefore, a novel local vaccine that can cover various topotypes of viruses is required. Two virus strains, O/Boeun/SKR/2017 and A/Yeoncheon/SKR/2017, were cultured up to the pilot scale based on the optimized conditions set up on the flask scale. FMDV particles (146S) of 2 µg/mL or more were obtained from the virus culture supernatant using a 100 L bioreactor. The viruses were fully inactivated using binary ethylenimine within 16 h through two inactivation cycles and mixed with an adjuvant into a bivalent vaccine (types O and A) consisting of 15 µg viruses per strain. The experimental bivalent vaccine showed a broad spectrum of high neutralizing antibody titers against heterologous viruses, including type O Cathay strain and type A Asia topotypes, except for GVII. The 50% protective dose was determined as 12.5 for O/Boeun/SKR/2017 and 15.6 for A/Yeoncheon/SKR/2017. Collectively, we expect that the bivalent vaccine could protect against FMDV types O and A circulating in South Korea and neighboring countries. To our knowledge, this is the first report demonstrating that the vaccine strains could be successfully scaled-up to a 100 L bioreactor, with the determination of its protective efficacy in pigs.

Molecular Basis of Antigenic Drift in Serotype O Foot-and-Mouth Disease Viruses (2013–2018) from Southeast Asia

“…Currently, three topotypes of serotype O viruses (SEA, Cathay and ME-SA) are circulating in the region ( Table 1 ), although historically SEA countries were home to SEA and Cathay topotype viruses. The O/ME-SA/PanAsia strain spread to SEA countries in early 2000, causing devastating economic consequences [ 12 , 13 , 14 ]. One decade later, in early 2010, another ME-SA strain (O/Ind-2001) from the Indian subcontinent spread to these countries [ 22 ].…”

“…Thus, it appears that the existing v / s are broadly cross-reactive and can provide protection against the circulating topotypes, except Cathay viruses, as demonstrated previously using O 1 /Campos v / s [ 24 , 25 ]. Several studies, mainly from South Korea, have reported the suitability of new putative strains for use in both pigs and cattle in their control programs [ 13 , 14 , 26 ].…”

“…Therefore, although these v / s did not provide in vitro protection, it is possible that some protection could be observed in vivo, especially when high-antigen-payload vaccines are used. Indeed, a recent study involving a high-potency O/SKR/BOEUN/2017 vaccine (12.5 PD 50 ) exhibited in vitro protection against Cathay virus [ 13 , 14 ]. In addition, a better in vivo correlation protection has been established, combining both virus neutralization test results and the T-cell responses [ 34 ], which was out of the scope of this study.…”

“…Along with three usual strains O/SEA/Mya-98, O/Middle East-South Asia (ME-SA)/PanAsia and Cathay, a new O/ME-SA/Ind-2001 lineage, has been circulating in this region since 2015 and, have now spread to most of the SEA countries ( Table 1 ). Although vaccination is the key to controlling FMD, the available vaccines are not able to provide enough cross-protection as outbreaks have been still seen in South Korea since 2010 even with repeated vaccinations [ 12 , 13 , 14 ]. Therefore, a regular vaccine-matching test of circulating viruses with the existing vaccines in antigenic reserves is required, and if necessary, a broadly cross-reacting vaccine strain should be used in vaccination programs.…”

Molecular evolution, diversity, and adaptation of foot-and-mouth disease virus serotype O in Asia

“…Although vaccination is the key to control serotype O FMD, the available vaccines are not able to provide enough cross-protection as outbreaks still occurred despite repeated vaccinations ( Mahapatra et al, 2017 ; Lee et al, 2020 ; Park et al, 2021 ). The vaccines used showed a good match with the O/SEA and O/ME-SA viruses, whereas none of the recently circulating O/Cathay viruses were protected by any of the vaccine strains, including the existing O/Cathay vaccine, indicating an antigenic drift and the urgency to develop new vaccine strains ( Upadhyaya et al, 2021 ).…”