Development of Vaccines for Poultry Against H5 Avian Influenza Based on Turkey Herpesvirus Vector

Avian influenza (AI) remains a major threat to public health as well as to the poultry industry. AI vaccines are considered a suitable tool to support AI control programs in combination with other control measures such as good biosecurity and monitoring programs. We constructed recombinant turkey herpesvirus (HVT) vector vaccines expressing the hemagglutinin gene of AI virus H5 subtype (rHVT‐H5) and evaluated their characteristics and efficacy against AI. We found that the cytomegalovirus (CMV) promoter is the most suitable for expression of the hemagglutinin gene among three promoters we evaluated. The rHVT‐H5 vaccine did not cause any adverse reactions and did not revert to virulence after passages in chicken. Finally, efficacy of the rHVT‐H5 vaccine was evaluated. We demonstrated that it provided protection against diverse AI H5 viruses belonging to different clades and reduced virus shedding from the challenged chicken. We also proved that efficacy provided by the rHVT‐H5 vaccine was not significantly affected by presence of maternally derived antibodies (MDA) against AI virus. Furthermore, the rHVT‐H5 vaccine could be applicable to the differentiating infected from vaccinated animals (DIVA) strategy. In summary, we successfully developed a HVT vector AI vaccine that possesses features that could be beneficial to AI control

Recombinant Chimeric Transmissible Gastroenteritis Virus (TGEV)—Porcine Epidemic Diarrhea Virus (PEDV) Virus Provides Protection against Virulent PEDV

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus causing high morbidity and mortality in porcine herds worldwide. Although both inactivated and live attenuated vaccines have been extensively used, the emergence of highly virulent strains and the recurrent outbreaks even in vaccinated farms highlight the need of effective vaccines. Engineering of genetically defined live attenuated vaccines is a rational approach for novel vaccine development. In this line, we engineered an attenuated virus based on the transmissible gastroenteritis virus (TGEV) genome, expressing a chimeric spike protein from a virulent United States (US) PEDV strain. This virus (rTGEV-RS-SPEDV) was attenuated in highly-sensitive five-day-old piglets, as infected animals did not lose weight and none of them died. In addition, the virus caused very minor tissue damage compared with a virulent virus. The rTGEV-RS-SPEDV vaccine candidate was also attenuated in three-week-old animals that were used to evaluate the protection conferred by this virus, compared with the protection induced by infection with a virulent PEDV US strain (PEDV-NVSL). The rTGEV-RS-SPEDV virus protected against challenge with a virulent PEDV strain, reducing challenge virus titers in jejunum and leading to undetectable challenge virus RNA levels in feces. The rTGEV-RS-SPEDV virus induced a humoral immune response specific for PEDV, including neutralizing antibodies. Altogether, the data indicated that rTGEV-RS-SPEDV is a promising vaccine candidate against virulent PEDV infectionThis research was funded by grants from the Government of Spain (BIO2013-42869-R and BIO2016-75549-R AEI/FEDER, UE), Ceva Animal Health, the European Zoonotic Anticipation and Preparedness Initiative (ZAPI) (IMI_JU_115760), and the U.S. National Institutes of Health (NIH) (2P01AI060699 awarded to L.E. and I.S.).Peer reviewe

Clones y vectores infectivos derivados de coronavirus y sus aplicaciones

Referencia OEPM: P9902673.-- Fecha de solicitud: 03/12/1999.-- Titular: Consejo Superior de Investigaciones Científicas (CSIC).Clones y vectores infectivos derivados de coronavirus y sus aplicaciones. El clon infectivo derivado de un coronavirus comprende un cDNA que codifica el gRMA de un coronavirus clonado bajo una secuencia promotora de la transcripción. El vector viral recombinante comprende un clon infectivo modificado para contener un ácido nucleico heterólogo insertado en dicho clon infectivo bajo condiciones que permiten la expresión de dicho ácido nucleico heterólogo. Los clones y vectores infectivos son útiles tanto en investigación básica como aplicada, en el desarrollo de sistemas de expresión eficientes de productos de interés (proteínas, enzimas, anticuerpos, etc.), vectores vacunales y terapia génica.Peer reviewe

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo