Evaluation of the Cross-Protective Efficacy of a Chimeric PRRSV Vaccine against Two Genetically Diverse PRRSV2 Field Strains in a Reproductive Model

Abstract

Despite the routine use of porcine reproductive and respiratory syndrome (PRRS)-modified live vaccines, serious concerns are currently being raised due to their quick reversion to virulence and limited cross-protection against divergent PRRS virus (PRRSV) strains circulating in the field. Therefore, a PRRS chimeric vaccine (JB1) was produced using a DNA-launched infectious clone by replacing open reading frames (ORFs) 3–6 with those from a mixture of two genetically different PRRSV2 strains (K07–2273 and K08–1054) and ORF1a with that from a mutation-resistant PRRSV strain (RVRp22) exhibiting an attenuated phenotype. To evaluate the safety and cross-protective efficacy of JB1 in a reproductive model, eight PRRS-negative pregnant sows were purchased and divided into four groups. Four sows in two of the groups were vaccinated with JB1, and the other 4 sows were untreated at gestational day 60. At gestational day 93, one vaccinated group and one nonvaccinated group each were challenged with either K07–2273 or K08–1054. All of the sows aborted or delivered until gestation day 115 (24 days post challenge), and the newborn piglets were observed up to the 28th day after birth, which was the end of the experiment. Overall, pregnant sows of the JB1-vaccinated groups showed no meaningful viremia after vaccination and significant reductions in viremia with K07–2273 and K08–1054, exhibiting significantly higher levels of serum virus-neutralizing antibodies than non-vaccinated sows. Moreover, the JB1-vaccinated groups did not exhibit any abortion due to vaccination and showed improved piglet viability and birth weight. The piglets from JB1-vaccinated sows displayed lower viral concentrations in serum and fewer lung lesions compared with those of the piglets from the nonvaccinated sows. Therefore, JB1 is a safe and effective vaccine candidate that confers simultaneous protection against two genetically different PRRSV strains.

Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody

“…On the other hand, the neutralizing antibody titers against vCSL1-GP5-wt were measured as low, at 1.00 ± 2.00 (log 2 ) at 42 dpi and 4.00 ± 2.83 (log 2 ) at 19 dpc, compared to those for the homologous virus. This phenomenon is consistent with other studies on glycosylation alteration of PRRSV GP5, and is still noticeably meaningful, inducing an increase of at least 3 (log 2 ) post-challenge [ 20 , 42 , 43 , 44 ].…”

“…The backbone virus used in this study, vCSL1-GP5-wt, was prepared by replacing the ectodomain of vCSL1, belonging to lineage-5, with the lineage-1 strain [ 8 ]. A report on chimeric vaccine candidates made by different lineage viruses, similar to our candidate, suggested a defense against a heterogenous challenge [ 43 , 45 ]. We expect that vCSL1-GP5-N44S can defend against lineage-1 and -5 simultaneously, but further testing is needed [ 8 ].…”

“…In a study in which neutralizing antibodies were transferred and then challenged using a young piglet model, it was suggested that neutralizing antibodies in blood at 3 (log 2 ) or higher could clear viremia [ 42 ]. Other studies found that high levels of neutralizing antibodies were associated with a low viral load in the blood post-challenge [ 25 , 43 ]. In this study, neutralizing antibodies to homologous strain in pigs inoculated with vCSL1-GP5-N44S reached a maximum of 4.50 ± 3.0 (log 2 ) at 42 dpi and reached 8.25 ± 0.96 (log 2 ) post-challenge.…”

“…In a study, a synthetic PRRS vaccine candidate showed high levels (8–9 log genome copies/mL) of viremia, similar to the pathogenic wild-type virus, subsequently showing protection in a challenge test [ 39 ]. In other studies, vaccine candidate strains showed protective ability in a challenge infection after a lower level of viremia than that of the highly pathogenic control virus [ 25 , 40 , 43 , 45 ]. Meanwhile, in another study, half of the vaccinated pigs were induced with viremia, while the others were not, and neutralizing antibodies appeared in all animals [ 23 ].…”

“…Developing a vaccine against PRRSV is challenged by the genetic variability associated with viral replication properties [ 15 ]. PRRS-2 is divided into nine lineages based on the genome, and the defense against different lineages is partial, depending on the vaccine candidate strain [ 43 ]. Even with two vaccine candidates of the same lineage, one study showed different protective abilities against the same challenge strain [ 45 ].…”