Abstract
Classical swine fever virus (CSFV) is a highly contagious pathogen, which pose continuous threat to the swine industry. Though most attenuated vaccines are effective, they fail to serologically distinguish between infected and vaccinated animals, hindering CSFV eradication. Beneficially, nanoparticles (NPs)-based vaccines resemble natural viruses in size and antigen structure, and offer an alternative tool to circumvent these limitations. Using self-assembling NPs as multimerization platforms provides a safe and immunogenic tool against infectious diseases. This study presented a novel strategy to display CSFV E2 glycoprotein on the surface of genetically engineered self-assembling NPs. Eukaryotic E2-fused protein (SP-E2-mi3) could self-assemble into uniform NPs as indicated in transmission electron microscope (TEM) and dynamic light scattering (DLS). SP-E2-mi3 NPs showed high stability at room temperature. This NP-based immunization resulted in enhanced antigen uptake and up-regulated production of immunostimulatory cytokines in antigen presenting cells (APCs). Moreover, the protective efficacy of SP-E2-mi3 NPs was evaluated in pigs. SP-E2-mi3 NPs significantly improved both humoral and cellular immunity, especially as indicated by the elevated CSFV-specific IFN-γ cellular immunity and >10-fold neutralizing antibodies as compared to monomeric E2. These observations were consistent to in vivo protection against CSFV lethal virus challenge in prime-boost immunization schedule. Further results revealed single dose of 10 μg of SP-E2-mi3 NPs provided considerable clinical protection against lethal virus challenge. In conclusion, these findings demonstrated that this NP-based technology has potential to enhance the potency of subunit vaccine, paving ways for nanovaccine development.
Highlights
Classical swine fever (CSF), characterized by typical clinical symptoms including fever, anorexia, ataxia and respiratory problems, can result in high morbidity and mortality in pigs [1, 2]
The results showed that fusion protein signal peptide (SP)-E2-mi3 could self-assemble into uniform NPs, which had an approximate diameter of 25–35 nm (Figure 1C)
The widespread application of C-strain attenuated vaccine has suppressed the endemic outbreak to a great extent, Classical swine fever virus (CSFV) is still spreading and circulating in many countries including China
Summary
Classical swine fever (CSF), characterized by typical clinical symptoms including fever, anorexia, ataxia and respiratory problems, can result in high morbidity and mortality in pigs [1, 2]. Outbreaks of CSF led to significant economic losses in the pig industry worldwide, including Central and South America, Africa and Asia. C-strain vaccine does not allow serological differentiation between infected and vaccinated animals (DIVA), which severely hinder the control and eradication of CSFV [6, 8]. As the main protective antigen of CSFV, E2-based subunit vaccine can induce protective neutralizing antibodies, and it allows DIVA by monitoring anti-CSFV Erns antibodies [9]. It is the preferred target for the development of subunit vaccines [10, 11]
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