Advanced Foot-And-Mouth Disease Vaccine Platform for Stimulation of Simultaneous Cellular and Humoral Immune Responses

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.

The HSP70-fused foot-and-mouth disease epitope elicits cellular and humoral immunity and drives broad-spectrum protective efficacy

“…Considering previous studies, we performed an intensive study that used PRR ligands and cytokines as new FMD vaccine adjuvants to simultaneously enhance cellular and humoral immune responses in target animal species (cattle and pigs) 14 . In addition, we inserted 3A, a universal T cell epitope, and HSP70, which acts as a linker for innate and adaptive immune responses as “chaperokines” to the FMDV VP1 region to develop immunopotent FMD vaccine strains that stimulate strong, simultaneous cellular and humoral immune responses in mice and pigs 15 . Based on these findings, we developed a new porcine recombinant protein, rpHSP70-AD (Fig.…”

“…Purified antigen (inactivated FMDV) was prepared in BHK-21 cells infected with FMDV O/TWN/97-R (GenBank AY593823), A22/IRAQ-R (GenBank AY593763), O/SKR/BE/2017 (GenBank MG983730), and A/SKR/YC/2017 (GenBank KY766148.1) as previously described 14 , 15 .…”

“…The housing room was set to a 12/12 h light/dark cycle, a temperature of about 22 °C, and relative air humidity of about 50%. Studies were performed according to institutional guidelines and with approval from the Ethics Committee of the Animal and Plant Quarantine Agency (Accreditation number IACUC-2019–185) 14 , 15 .…”

“…To evaluate the efficacy of the novel recombinant protein rpHSP70-AD as an FMD vaccine adjuvant, an oil emulsion-free test vaccine that included rpHSP70-AD as an adjuvant was produced, following the protocol published by Lee et al 15 . Then, early, mid-term, and long-term immunity and the induced immune memory response was observed in mice.…”

“…Meanwhile, we proposed novel adjuvants optimized for cattle and pigs, especially adjuvants and FMD vaccine compositions that simultaneously enhance cellular and humoral immune responses by selecting PRR ligands as immunostimulants 14 . We reported the development of a recombinant immunopotent FMD vaccine strain and an advanced FMD vaccine platform by spiking the active sites of the immune-enhancing molecules HSP70 and T cell epitope 3A onto the surface of FMDV 15 .…”