Research

QA prime-boost vaccination strategy in prevent serotype O FMDV infection using a "single-cycle" alphavirus vector and empty capsid particles

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Abstract

Introduction Foot-and-mouth disease (FMD) remains one of the most economically important infectious diseases of production animals globally. Vaccination can help to control this disease, however, current vaccines based on chemically inactivated FMDV, are imperfect and there is a need for new, safe and effective vaccines to control FMD. There is no cross protection between the 7 serotypes but serotype O is the most abundant globally. Material and methods The FMDV capsid protein precursor (P1-2A) of strain O1 Manisa has been expressed with the FMDV 3C protease (3Cpro) using a “single cycle” packaged alphavirus self-replicating RNA based on Semliki Forest virus (SFV). Purified O1 Manisa empty capsid particles (ECs) have been prepared using a recombinant vaccinia virus expression system. Cattle have been vaccinated with the SFV-FMDV vectors and boosted subsequently with the ECs and then challenged with serotype O FMDV. The immune response against FMDV achieved by vaccination and infection status following challenge has been determined. Results In cattle vaccinated once with these rSFV-FMDV vectors alone, anti-FMDV antibodies were elicited but the immune response was insufficient to give protection against FMDV challenge. However, the vaccination with these vectors resulted in a much stronger immune response against FMDV post-challenge than in naïve animals. In subsequent experiments, cattle were sequentially vaccinated with the rSFV-FMDV followed by recombinant FMDV empty capsid particles prior to challenge. Animals given a primary vaccination with the rSFV-FMDV vector and then boosted with FMDV empty capsids showed a strong anti-FMDV antibody response prior to challenge. Following challenge with serotype O FMDV, the cattle were protected against disease and no FMDV RNA was detected in their sera. Discussion This prime-boost system, using reagents that can be generated outside of high-containment facilities, offers significant advantages to achieve control of FMD by vaccination.