A Plant-Produced Porcine Parvovirus 1-82 VP2 Subunit Vaccine Protects Pregnant Sows against Challenge with a Genetically Heterologous PPV1 Strain.

Porcine parvovirus (PPV) causes reproductive failure in sows, and vaccination remains the most effective means of preventing infection. The NADL-2 strain has been used as a vaccine for ~50 years; however, it does not protect animals against genetically heterologous PPV strains. Thus, new effective and safe vaccines are needed. In this study, we aimed to identify novel PPV1 strains, and to develop PPV1 subunit vaccines. We isolated and sequenced PPV1 VP2 genes from 926 pigs and identified ten PPV1 strains (belonging to Groups C, D and E). We selected the Group D PPV1-82 strain as a vaccine candidate because it was close to the highly pathogenic 27a strain. The PPV1-82 VP2 protein was produced in Nicotiana benthamiana. It formed virus-like particles and exhibited a 211 agglutination value. The PPV1-190313 strain (Group E), isolated from an aborted fetus, was used as the challenging strain because it was pathogenic. The unvaccinated sow miscarried at 8 days postchallenge, and mummified fetuses were all PPV1-positive. By contrast, pregnant sows vaccinated with PPV1-82 VP2 had 9-11 Log2 antibody titers and produced normal fetuses after PPV1-190313 challenge. These results suggest the PPV1-82 VP2 subunit vaccine protects pregnant sows against a genetically heterologous PPV1 strain by inducing neutralizing antibodies.

Differential effects of dual antiplatelet therapy in patients presented with acute coronary syndrome vs. stable ischaemic heart disease after coronary artery bypass grafting.

AIMS: The current study sought to evaluate whether long-term clinical outcomes according to the use of dual antiplatelet therapy (DAPT) or single antiplatelet therapy (SAPT) differed between acute coronary syndrome (ACS) and stable ischaemic heart disease (SIHD) patients who underwent coronary artery bypass grafting surgery (CABG). METHODS AND RESULTS: Between January 2001 and December 2017, 3199 patients with ACS (55.3%) and 2583 with SIHD (44.7%) who underwent isolated CABG were enrolled. The study population was stratified using DAPT or SAPT in ACS patients and SIHD patients. The primary outcome was a cardiovascular death or myocardial infarction (MI) at 5 years. After CABG, DAPT was more frequently used in patients with ACS than in those with SIHD [n = 1960 (61.3%) vs. n = 1313 (50.8%), P < 0.001]. Among patients with ACS, the DAPT group showed a significantly lower risk of cardiovascular death or MI at 5 years than the SAPT group [DAPT vs. SAPT, 4.0% vs. 7.8%, hazard ratio (HR) 0.521, 95% confidence interval (CI) 0.339-0.799; P = 0.003]. In contrast, among patients with SIHD, there was no significant difference in the rate of cardiovascular death or MI at 5 years between the use of DAPT and SAPT (4.0% vs. 4.0%, HR 0.991, 95% CI 0.604-1.626; P = 0.971). These findings were robust to multiple sensitivity analyses and competing risk analysis. In the subgroup analysis, the use of DAPT was associated with a significantly lower risk of cardiovascular death or MI among SIHD patients with a previous percutaneous coronary intervention (PCI), with a significant interaction between the use of DAPT and PCI history (interaction P = 0.011). CONCLUSION: Among ACS patients who underwent CABG, the use of DAPT was associated with lower cardiovascular death or MI than the use of SAPT, but this was not the case in SIHD patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03870815.

2,3-Diarylbenzopyran derivatives as a novel class of selective cyclooxygenase-2 inhibitors.

A new series of cyclooxygenase-2(COX-2) inhibitors with naturally occurring flavone as the main skeleton has been synthesized and their biological activities were evaluated for cyclooxygenase inhibitory activity. Rational structural modifications were applied to potent COX-2 inhibitors to obtain the desired pharmacokinetic profiles for improved oral anti-inflammatory activity.