No abstract

As PCV2d infection has been continuously reported in swine farms in which pigs were vaccinated with PCV2a- or 2d-based vaccines, we attempted to develop a novel vaccine using a PCV2d-based capsid to enhance its protective efficacy. In this study, recombinant virus-like particles (VLPs) of rPCV2a, rPCV2b and rPCV2d were synthesized from the capsid proteins of PCV2a, PCV2b and PCV2d field isolates, respectively. A cross-neutralization assay between the VLPs induced antisera and the field isolates demonstrated the broad cross-neutralizing activities of the rPCV2d-induced antisera. Then, the protective efficacy of rPCV2d as a vaccine candidate was investigated in commercial pigs by rPCV2d vaccination and a single- or dual-challenge infection using a PCV2d strain and a type 1 PRRSV strain. High levels of anti-PCV2d IgG and neutralizing antibodies were induced 3 weeks after vaccination. After the challenge infection, the average ADWG values of the vaccinated group were higher than those of the unvaccinated group. None or a significantly low amount of (p < 0.05) reduced PCV2 genomic DNA was found in the blood, saliva and tissues of the vaccinated pigs, when compared to the unvaccinated group. Moreover, macroscopic and microscopic lesions in the tissues were significantly (p < 0.05) reduced in the vaccinated groups. This study therefore suggests that rPCV2d may be highly useful for the control of diverse field genotypes.

Background Porcine circovirus type 2 (PCV2) is a small single-stranded DNA virus and a primary cause of PCV-associated diseases (PCVAD) that result insubstantial economic loss for swine farms. Between 2016 and 2018, PCV2 field viruses were isolated from PCVAD-affected swine farms in South Korea and investigated for genetic and antigenic heterogeneity. Results The genetic analysis of ORF2 showed that the genotype of the Korean PCV2 field isolates has been rapidly shifted from PCV2a or 2b to mutant PCV2b known as PCV2d with 82.6 to 100% amino acid sequence similarity. PCV2-specific monoclonal antibodies (mAbs) demonstrated variable antigen-binding activity to four representative Korean PCV2 field isolates [QIA215 (PCV2a), QIA418 (PCV2b), QIA169 (PCV2d), and QIA244 (PCV2d)] without genotype specificity, and one mAb showed neutralization activity to QIA215. In a cross-virus neutralization assay using anti-PCV2 sera of pigs and guinea pigs injected with a commercial vaccine and the Korean PCV2 field isolates, the anti-porcine sera of a commercial vaccine had high neutralization activity against QIA215 and QIA418 with statistically lower activity against PCV2d viruses. Anti-guinea pig sera of QIA215, QIA418, QIA169, and a commercial vaccine had high neutralization activity against all of the viruses with significantly lower activity against QIA244. Importantly, anti-guinea pig sera of QIA244 had high neutralization activity against all of the viruses. Conclusions This study confirmed genetic and antigenic diversity among recent PCV2 field isolates in Korean swine farms, and the strain-based difference in virus neutralization capability should be considered for more effective control by vaccination.

On December 3, 2014, a type O foot-and-mouth disease (FMD) outbreak began in Korea. Although vaccinations were administered, FMD cases increased steadily for five months, and reached 185 cases by April 2015. Most of the affected animals were pigs, which are vulnerable to vaccination. The FMD virus belonged to the South-East Asia (SEA) topotype that had been observed three times in Korea between April 2010 and July 2014. However, the FMD virus isolated in December 2014 had a unique feature; that is, partial deletion of the 5′ non-coding region, a deletion not seen in previous SEA topotype isolates identified in Korea. We conclude that this outbreak included the introduction of a new FMD strain to Korea, and that Korea was now affected by genetically similar FMD virus strains that are related to those from neighboring countries.

Because the currently available vaccines against foot-and-mouth disease (FMD) provide no protection until 4 to 7 days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is the application of antiviral agents. Combination treatment strategies have been used to enhance the efficacy of antiviral agents, and such strategies may be advantageous in overcoming viral mechanisms of resistance to antiviral treatments. We have developed recombinant adenoviruses (Ads) for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-␣␥) as well as 3 small interfering RNAs (Ad-3siRNA) targeting FMDV mRNAs encoding nonstructural proteins. The antiviral effects of Ad-porcine IFN-␣␥ and Ad-3siRNA expression were tested in combination in porcine cells, suckling mice, and swine. We observed enhanced antiviral effects in porcine cells and mice as well as robust protection against the highly pathogenic strain O/Andong/ SKR/2010 and increased expression of cytokines in swine following combination treatment. In addition, we showed that combination treatment was effective against all serotypes of FMDV. Therefore, we suggest that the combined treatment with Adporcine IFN-␣␥ and Ad-3siRNA may offer fast-acting antiviral protection and be used with a vaccine during the period that the vaccine does not provide protection against FMD. IMPORTANCEThe use of current foot-and-mouth disease (FMD) vaccines to induce rapid protection provides limited effectiveness because the protection does not become effective until a minimum of 4 days after vaccination. Therefore, during outbreaks antiviral agents remain the only available treatment to confer rapid protection and reduce the spread of foot-and-mouth disease virus (FMDV) in livestock until vaccine-induced protective immunity can become effective. Interferons (IFNs) and small interfering RNAs (siRNAs) have been reported to be effective antiviral agents against FMDV, although the virus has associated mechanisms of resistance to type I interferons and siRNAs. We have developed recombinant adenoviruses for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-␣␥) as well as 3 small interfering RNAs (Ad-3siRNA) to enhance the inhibitory effects of these antiviral agents observed in previous studies. Here, we show enhanced antiviral effects against FMDV by combination treatment with Ad-porcine IFN-␣␥ and Ad-3siRNA to overcome the mechanisms of resistance of FMDV in swine.