Distinct Pathological Changes in Preweaning Mice Infected with Live-Attenuated Rift Valley Fever Virus Strains.

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Middle East. Live-attenuated RVF vaccines have been studied for both veterinary and human use due to their strong immunogenicity and cost-effective manufacturing. The live-attenuated MP-12 vaccine has been conditionally approved for veterinary use in the U.S.A., and next-generation live-attenuated RVF vaccine candidates are being actively researched. Assessing the virulence phenotype of vaccine seeds or lots is crucial for managing vaccine safety. Previously, preweaning 19-day-old outbred CD1 mice have been used to evaluate the MP-12 strain. This study aimed to characterize the relative virulence of three live-attenuated RVF vaccine strains in 19-day-old inbred C57BL/6 mice: the recombinant MP-12 (rMP-12), the RVax-1, and the ∆NSs-∆NSm-rZH501 strains. Although this mouse model did not show dose-dependent pathogenesis, mice that succumbed to the infection exhibited distinct brain pathology. Mice infected with ∆NSs-∆NSm-rZH501 showed an infiltration of inflammatory cells associated with infected neurons, and focal lesions formed around virus-infected cells. In contrast, mice infected with rMP-12 or RVax-1 showed a minimal association of inflammatory cells in the brain, yet the virus spread diffusely. The preweaning model is likely useful for evaluating host responses to attenuated RVFV strains, although further refinement may be necessary to quantitate the virulence among different RVFV strains or vaccine lots.

Antibodies targeting the glycan cap of Ebola virus glycoprotein are potent inducers of the complement.

Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. Both neutralization and some of the Fc-mediated effects are known to contribute the protection conferred by antibodies of various epitope specificities. At the same time, the role of the complement system remains unclear. Here, we compare complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of GP. Binding of GC-specific mAbs to GP induces complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs. In the mouse model of EBOV infection, depletion of the complement system leads to an impairment of protection exerted by one of the GC-specific, but not MPER-specific mAbs. Our data suggest that activation of the complement system represents an important mechanism of antiviral protection by GC antibodies.

Advancements in Rift Valley fever vaccines: a historical overview and prospects for next generation candidates.

Rift Valley fever (RVF) is a zoonotic viral disease transmitted by mosquitoes and causes abortion storms, fetal malformations, and newborn animal deaths in livestock ruminants. In humans, RVF can manifest as hemorrhagic fever, encephalitis, or retinitis. Outbreaks of RVF have been occurring in Africa since the early 20th century and continue to pose a threat to both humans and animals in various regions such as Africa, Madagascar, the Comoros, Saudi Arabia, and Yemen. The development of RVF vaccines is crucial in preventing mortality and morbidity and reducing the spread of the virus. While several veterinary vaccines have been licensed in endemic countries, there are currently no licensed RVF vaccines for human use. This review provides an overview of the existing RVF vaccines, as well as potential candidates for future studies on RVF vaccine development, including next-generation vaccines that show promise in combating the disease in both humans and animals.

Evaluations of rationally designed rift valley fever vaccine candidate RVax-1 in mosquito and rodent models.

Rift Valley fever (RVF) is a mosquito-borne zoonosis endemic to Africa and the Arabian Peninsula, which causes large outbreaks among humans and ruminants. Single dose vaccinations using live-attenuated RVF virus (RVFV) support effective prevention of viral spread in endemic countries. Due to the segmented nature of RVFV genomic RNA, segments of vaccine strain-derived genomic RNA could be incorporated into wild-type RVFV within co-infected mosquitoes or animals. Rationally designed vaccine candidate RVax-1 displays protective epitopes fully identical to the previously characterized MP-12 vaccine. Additionally, all genome segments of RVax-1 contribute to the attenuation phenotype, which prevents the formation of pathogenic reassortant strains. This study demonstrated that RVax-1 cannot replicate efficiently in orally fed Aedes aegypti mosquitoes, while retaining strong immunogenicity and protective efficacy in an inbred mouse model, which were indistinguishable from the MP-12 vaccine. These findings support further development of RVax-1 as the next generation MP-12-based vaccine for prevention of Rift Valley fever in humans and animals.

Evolución del virus dengue en el Ecuador: Período 2000 a 2015 / Evolution of dengue virus in Ecuador 2000-2015

Introducción. Actualmente la infección por virus dengue constituye una de las arbovirosis más importantes y de amplia distribución en las regiones tropicales y subtropicales del planeta. Objetivo. Determinar la evolución del virus dengue circulante en el Ecuador durante el periodo 2000 a 2015. Diseño. Estudio no experimental, transversal, de tipo descriptivo y correlacional; Lugar. Unidades de salud del Ecuador. Participantes. Muestras tomadas a sospechosos de dengue con menos de 5 días de iniciada su enfermedad. Resultados. En el año 2000 se tuvo la presencia de los 4 serotipos, con predominio del DEN3 durante 2001 al 2006, coincidentes con los incrementos de casos del 2000, 2001 y 2005; en el año 2004 reapareció el virus DEN1 y los años siguientes su presencia predominó entre 2007 y 2012, coincidiendo con el incremento de casos en el 2010. Del año 2011 al 2015 se presentaron 3 virus circulantes a la vez (DEN1, DEN2 y DEN4), en 2014 y 2015 hubo la presencia del virus DEN3, con predominio del virus DEN2 en 2013 y 2014 y virus DEN1 en 2015; y ha sido la provincia del Guayas la de mayor relación con los virus. Conclusiones. La presencia de varios serotipos de virus dengue circulando a la vez y su permanencia se debería a otros factores que están influenciando en el comportamiento del virus, con una variabilidad de los cuatro serotipos. Se debe fortalecer la vigilancia molecular de la circulación de serotipos, genotipos y linajes del virus dengue.

Introduction: Nowadays, the dengue virus infection is one of the most important arboviroses in the world's tropical and subtropical regions. Objective: To determine the evolution of the dengue virus circulating in Ecuador during the period 2000-2015. Design: Non-experimental, transversal, descriptive and correlational study. Setting: Health units of Ecuador. Participants: The samples were taken from dengue suspects with less than 5 days from the beginning of the disease. Results: In 2000, the four serotypes were present, with prevalence of DEN3 during 2001-2006 coinciding with the increase of cases in 2000, 2001 and 2005; in 2004, the DEN1 virus reappeared and, during the following years, its presence predominated between 2007 and 2012, coinciding with the increase of cases in 2010. From 2011 to 2015 three circulating viruses were present at the same time (DEN1, DEN2 and DEN4); in 2014 and 2015, the DEN3 virus predominated; the predominance of the DEN2 virus was in 2013 and 2014, and of the DEN1 virus in 2015. The province of Guayas had the greatest relation with the virus. Conclusions: The presence and permanence of several serotypes of dengue virus circulating at the same time is due to other factors influencing the virus behavior and variability of the four serotypes. The molecular surveillance of the circulating serotypes, genotypes and dengue virus lineages should be strengthened.