Abstract

Currently available commercial foot-and-mouth disease (FMD) vaccines have various limitations, such as the slow induction and short-term maintenance of antibody titers. Therefore, a novel FMD vaccine that can rapidly induce high neutralizing antibody titers to protect the host in early stages of an FMD virus infection, maintain high antibody titers for long periods after one vaccination dose, and confer full protection against clinical symptoms by simultaneously stimulating cellular and humoral immunity is needed. Here, we developed immunopotent FMD vaccine strains A-3A and A-HSP70, which elicit strong initial cellular immune response and induce humoral immune response, including long-lasting memory response. We purified the antigen (inactivated virus) derived from these immunopotent vaccine strains, and evaluated the immunogenicity and efficacy of the vaccines containing these antigens in mice and pigs. The immunopotent vaccine strains A-3A and A-HSP70 demonstrated superior immunogenicity compared with the A strain (backbone strain) in mice. The oil emulsion-free vaccine containing A-3A and A-HSP70 antigens effectively induced early, mid-term, and long-term immunity in mice and pigs by eliciting robust cellular and humoral immune responses through the activation of co-stimulatory molecules and the secretion of proinflammatory cytokines. We successfully derived an innovative FMD vaccine formulation to create more effective FMD vaccines.

Highlights

  • Foot-and-mouth disease (FMD) is a highly contagious viral disease that typically affects cloven-hoofed livestock and leads to huge economic losses in the livestock industry due to its rapid transmission, severe reduction in animal productivity, and high mortality in newborn animals caused by myocarditis [1]

  • Considering the time required for a B cell-mediated increase in antibody levels after vaccination, the universal T cell epitope 3A (15 a.a.) and the active site (20 a.a) of the 70-kDa heat shock protein (HSP70) were selected as the immunopotent candidate materials for simultaneous induction of cellular and humoral immune responses

  • The universal T cell epitope 3A can increase the initial T-cell-mediated cellular immune response after vaccination, and HSP70 serves as a linker between innate and adaptive immune responses, as well as induces long-term immunity and memory response [17,18,19]

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Summary

Introduction

Foot-and-mouth disease (FMD) is a highly contagious viral disease that typically affects cloven-hoofed livestock and leads to huge economic losses in the livestock industry due to its rapid transmission, severe reduction in animal productivity, and high mortality in newborn animals caused by myocarditis [1]. FMD is categorized as a category I livestock epidemic by the Act on the Prevention of Livestock Epidemics in the Republic of Korea and is managed by the World Organization for Animal Health (Office International des Épizooties; OIE). Susceptible species include domestic ruminants, including cattle, water buffaloes, camels, sheep, goats, and pigs, and about 70 or more wild animal species. This disease is accompanied by a high fever and causes vesicle formation on the mouth, tongue, snout, nose, teats, hooves, and other hairless parts of the skin [3].

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