Key result
Inoculation with a low dose of codon-pair deoptimized FMDV serotype O caused no clinical disease but failed to induce protective immunity, whereas a higher dose resulted in clinical disease.
Why the study?
Control and prevention measures against FMDV, such as vaccines, are urgently needed, and codon pair deoptimization represents a novel strategy for viral attenuation.
Does codon-pair deoptimization of the P1 region attenuate FMDV serotype O and induce protective immunity in pigs?
Does codon-pair deoptimization of the P1 region attenuate FMDV serotype O and induce protective immunity in pigs?
Codon-pair deoptimization of FMDV serotype O successfully attenuates the virus but fails to elicit protective immunity at safe doses in swine.
Answers are grounded in this paper and cite their sources.
Codon-pair deoptimization attenuates FMDV in swine without protective immunity at safe doses; leaves open its vaccine potential pending further optimization.
Foot-and-mouth-disease (FMD), caused by the FMD virus, is a contagious disease affecting cloven-hoofed animals. Since outbreaks often cause significant economic impact, control and prevention measures against FMDV, such as vaccines, are urgently needed especially in endemic regions. The use of inactivated whole-virus vaccines has led to the eradication of FMD in many industrialized nations. Nonetheless, recent outbreaks in Europe have highlighted the virus’s potential for rapid spread and its capacity to inflict substantial economic losses. Codon pair deoptimization is a novel strategy for viral attenuation. In this study, we report the first application of this approach to the P1 capsid coding region of FMDV serotype O. A recombinant virus carrying the deoptimized P1 region was attenuated in vitro, as evidenced by reduced replication capacity in porcine LFBK-αvβ6 cells. In vivo evaluations further demonstrated that a substantially higher dose was required to induce clinical disease in pigs than with wild-type viruses. However, immunization with lower and innocuous doses did not result in protective immunity. These findings underscore both the potential and the challenges of utilizing codon pair deoptimization for developing safe and effective FMDV vaccine candidates, emphasizing that further optimization is necessary to achieve a desirable balance between attenuation and immunogenicity.
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Lorenz et al. (2026) studied Foot-and-mouth disease (n=6). OBUL-P1-CPD (codon-pair deoptimized FMDV serotype O) was evaluated on Clinical signs of FMD and protective immunity. Inoculation with a low dose of codon-pair deoptimized FMDV serotype O caused no clinical disease but failed to induce protective immunity, whereas a higher dose resulted in clinical disease.
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