Modified Vaccinia Virus Ankara as a Viral Vector for Vaccine Candidates against Chikungunya Virus

There is a need to develop a highly effective vaccine against the emerging chikungunya virus (CHIKV), a mosquito-borne Alphavirus that causes severe disease in humans consisting of acute febrile illness, followed by chronic debilitating polyarthralgia and polyarthritis. In this review, we provide a brief history of the development of the first poxvirus vaccines that led to smallpox eradication and its implications for further vaccine development. As an example, we summarize the development of vaccine candidates based on the modified vaccinia virus Ankara (MVA) vector expressing different CHIKV structural proteins, paying special attention to MVA-CHIKV expressing all of the CHIKV structural proteins: C, E3, E2, 6K and E1. We review the characterization of innate and adaptive immune responses induced in mice and nonhuman primates by the MVA-CHIKV vaccine candidate and examine its efficacy in animal models, with promising preclinical findings needed prior to the approval of human clinical trials.This research was supported by the ICRES (Integrated Chikungunya Research), a collaborative project supported by the European Union under the Health Cooperation Work Program of the 7th Framework Program (grant agreement 261202), a grant from the Spanish Ministerio de Ciencia e Innovación (SAF2008-02036), and a grant from Acción Estratégica en Salud from the ISCIII, grant MPY 388/18.S

A segmented form of foot-and-mouth disease virus interferes with standard virus: A link between interference and competitive fitness

AbstractSerial passage of foot-and-mouth disease virus (FMDV) in BHK-21 cells at high multiplicity of infection resulted in dominance of particles containing defective RNAs that were infectious by complementation in the absence of standard viral RNA. In the present study, we show that the defective FMDV particles interfere with replication of the cognate standard virus. Coinfections of defective FMDV with standard FMDV mutants that differ up to 151-fold in relative fitness have documented that the degree of interference is higher for low fitness than for high fitness standard virus. These comparisons suggest a likely overlap between those mechanisms of intracellular competition that underlie viral interference and those expressed as fitness differences between two viruses when they coinfect the same cells. Interference may contribute to the selective pressures that help maintain dominance of segmented defective RNAs over the standard FMDV genome

Auxiliary Companies of the Horticultural Sector as a Competitiveness Element: The Case of Almeria (Spain)

The horticultural model of Almeria (Spain) based on the operation of greenhouses is an international reference and has been considered as an economic miracle. Alongside this agricultural development has been the deployment of the diverse productive activity of auxiliary companies. The objective of this article is to understand how these companies operate and analyze their factors of competitiveness, competing needs, and future competitive improvements, taking as reference four of the most important subsectors (machinery, greenhouse infrastructure, plastics, and seeds). The Delphi method was used and through a panel of experts the conditioning factors of each of the variables to be analyzed (factors, needs, and competitiveness improvements) was chosen. Of the 120 companies that were sent questionnaires, 72 participated. The sectors that make up the auxiliary companies are heterogeneous and therefore the results obtained have differed among them. The synergies between the greenhouse crops and the auxiliary companies are an example of diversification of productive activity that can be extrapolated to other production areas worldwide. The future of the auxiliary companies is linked to that of the intensive agriculture and the key variables must be underscored by competitiveness and sustainability

Viral Genome Segmentation Can Result from a Trade-Off between Genetic Content and Particle Stability

The evolutionary benefit of viral genome segmentation is a classical, yet unsolved question in evolutionary biology and RNA genetics. Theoretical studies anticipated that replication of shorter RNA segments could provide a replicative advantage over standard size genomes. However, this question has remained elusive to experimentalists because of the lack of a proper viral model system. Here we present a study with a stable segmented bipartite RNA virus and its ancestor non-segmented counterpart, in an identical genomic nucleotide sequence context. Results of RNA replication, protein expression, competition experiments, and inactivation of infectious particles point to a non-replicative trait, the particle stability, as the main driver of fitness gain of segmented genomes. Accordingly, measurements of the volume occupation of the genome inside viral capsids indicate that packaging shorter genomes involves a relaxation of the packaging density that is energetically favourable. The empirical observations are used to design a computational model that predicts the existence of a critical multiplicity of infection for domination of segmented over standard types. Our experiments suggest that viral segmented genomes may have arisen as a molecular solution for the trade-off between genome length and particle stability. Genome segmentation allows maximizing the genetic content without the detrimental effect in stability derived from incresing genome length

The use of Polar Coordinates in the analysis of motor interaction in football according to the result.

The interactions of a Spanish football team of the Second A (10 official games) are analyzed, evaluating possible behavioral patterns that appear in a regular way in high level football. Observational methodology was used, by Polar Coordinates Analysis, to discover and evaluate the relationships generated between a considered focal behavior and the different conditioned categories, describing behavioral masses among the players. The matches were observed and recorded with an ad hoc observation instrument. The relations of dual character between the players taken as (focal behaviors) right midfielder and forward and the other players (conditioned conducts) were analyzed. The results show differences in the relationship established based on the outcome of the match. Matches that end with a favorable result, the right midfielder takes center stage, as a node of intermediation between the right centre back, left center back, left midfielder, and second striker. In these, the forward is clear receiver in the actions of completion. With the result of the unfavorable match, the connection networks change, generating a network of reciprocal interaction wider and different between the aforementioned player, right midfielder and the rest of the components, with special relation in the players that occupy the right back, left back, right centre back, right winger, left winger, second striker and forward. In these games the striker acquires a role of greater collaboration in the creation in offensive phases, participating as a node in the game network with intermediation functions

¿Qué hace diferentes a las grandes ligas profesionales?

Elite professional sport leagues are a global social-eco-nomical phenomenon. The fact that only few leagues achieve the elite category does not occur by chance. Four leagues from North America and five are European (NFL, MLB, NHL, NBA, EPL, Bundesliga, LaLiga, Serie A y Ligue 1) were evaluated. In order to demonstrate that are these leagues, and no other, the most signifi-cant ones, we have utilised non-linear methodologies (Power Laws, Entropy and probability of success) which allow us to go deep in the aspects that we understand as the most relevant ones: access to economic resources, competitive format, and competitive balance. All these nine leagues have access to more economical resources (Total Revenue: €45.712 M mill/season 2015) than the rest of the leagues in the world, constitute huge social transcendence, accumulate the best players worldwide and their components are confronted under different competition formats (closed or open leagues), but are highly competitive (Normalised Entropy: 0.976-0.998 – Performance Differential: 0.0159-0.0611). We can affirm that the main professional sport leagues present specific profiles, compared to the rest of the leagues in the world. The availability of economical resources, the competition format, and the uncertainty related to the match and league results are the factors that determine if a professional sport leagues can obtain global rele-vance, attracting millions of supporters worldwide and significant economical resourcesLas ligas deportivas profesionales son un fenómeno socioeconómico global. El hecho de que solo unas pocas ligas alcancen la categoría de élite no ocurre por casualidad. Se evaluaron cuatro ligas de Norteamérica y cinco europeas (NFL, MLB, NHL, NBA, EPL, Bundesliga, LaLiga, Serie A y Ligue 1). Para demostrar que son estas ligas, y no otras, las más importantes, se han utilizado metodologías no lineales (Leyes de potencia, Entropía y probabilidad de éxito) que nos permiten profundizar en los aspectos más relevantes: acceso a recursos económicos, formato competitivo y equilibrio competitivo. Todas ligas analizadas tienen acceso a recursos más económicos (ingresos totales: 45.712 millones de euros/temporada 2015) que el resto de las ligas del mundo, tienen una gran trascendencia social, acumulan a los mejores jugadores del mundo y sus componentes se enfrentan en diferentes formatos de competición (ligas cerradas o abiertas), pero son altamente competitivos (Entropía normalizada: 0.976-0.998-Diferencial de rendimiento: 0.0159-0.0611). Podemos afirmar que las principales ligas deportivas profesionales presentan perfiles específicos en comparación con el resto de las ligas del mundo. La disponibilidad de recursos económicos, el formato de competición y la incertidumbre relacionada con los resultados del partido y la liga son los factores que determinan si las ligas deportivas profesionales pueden obtener relevancia global, atrayendo a millones de seguidores en todo el mundo y recursos económicos significativosActividad Física y Deport

New vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines

Background: New vaccine designs are needed to control diseases associated with antigenically variable RNA viruses. Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that inflicts severe economic losses. Although the current whole-virus chemically inactivated vaccine has proven effective, it has led to new outbreaks of FMD because of incomplete inactivation of the virus or the escape of infectious virus from vaccine production premises. We have previously shown that serial passages of FMD virus (FMDV) C-S8c1 at high multiplicity of infection in cell culture resulted in virus populations consisting of defective genomes that are infectious by complementation (termed C-S8p260). Principal Finding: Here we evaluate the immunogenicity of C-S8p260, first in a mouse model system to establish a proof of principle, and second, in swine, the natural host of FMDV C-S8c1. Mice were completely protected against a lethal challenge with FMDV C-S8c1, after vaccination with a single dose of C-S8p260. Pigs immunized with different C-S8p260 doses and challenged with FMDV C-S8c1 either did not develop any clinical signs or showed delayed and mild disease symptoms. C-S8p260 induced high titers of both FMDV-specific, neutralizing antibodies and activated FMDV-specific T cells in swine, that correlated with solid protection against FMDV. Conclusions: The defective virus-based vaccine did not produce detectable levels of transmissible FMDV. Therefore, a segmented, replication-competent form of a virus, such as FMDV C-S8p260, can provide the basis of a new generation of attenuated antiviral vaccines with two safety barriers. The design can be extended to any viral pathogen that encodes trans-acting gene products, allowing complementation between replication-competent, defective forms. © 2010 Rodríguez-Calvo et al.Ministerio de Ciencia e Innovación, Spain, and European Union, Network of Excellence, EPIZONE (Contract # FOOD-CT-2006-016236). CIBERehd (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas) is funded by Instituto de Salud Carlos III. Work at Centro de Biología Molecular ‘‘Severo Ochoa’’ (CISC-UAM) was supported by an institutional grant from Fundación Ramón Arece

New Vaccine Design Based on Defective Genomes That Combines Features of Attenuated and Inactivated Vaccines

[Background] New vaccine designs are needed to control diseases associated with antigenically variable RNA viruses. Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that inflicts severe economic losses. Although the current whole-virus chemically inactivated vaccine has proven effective, it has led to new outbreaks of FMD because of incomplete inactivation of the virus or the escape of infectious virus from vaccine production premises. We have previously shown that serial passages of FMD virus (FMDV) C-S8c1 at high multiplicity of infection in cell culture resulted in virus populations consisting of defective genomes that are infectious by complementation (termed C-S8p260).[Principal Finding] Here we evaluate the immunogenicity of C-S8p260, first in a mouse model system to establish a proof of principle, and second, in swine, the natural host of FMDV C-S8c1. Mice were completely protected against a lethal challenge with FMDV C-S8c1, after vaccination with a single dose of C-S8p260. Pigs immunized with different C-S8p260 doses and challenged with FMDV C-S8c1 either did not develop any clinical signs or showed delayed and mild disease symptoms. C-S8p260 induced high titers of both FMDV-specific, neutralizing antibodies and activated FMDV-specific T cells in swine, that correlated with solid protection against FMDV.[Conclusions] The defective virus-based vaccine did not produce detectable levels of transmissible FMDV. Therefore, a segmented, replication-competent form of a virus, such as FMDV C-S8p260, can provide the basis of a new generation of attenuated antiviral vaccines with two safety barriers. The design can be extended to any viral pathogen that encodes trans-acting gene products, allowing complementation between replication-competent, defective forms.This research was supported by grants AGL2004-0049, AGL2007-61374, CSD2006-07 and BFU2008-02816/BMC from Ministerio de Ciencia e Innovación, Spain, and European Union, Network of Excellence, EPIZONE (Contract # FOOD-CT-2006-016236). CIBERehd (Centro de Investigacio´n Biome´dica en Red de Enfermedades Hepa´ticas y Digestivas) is funded by Instituto de Salud Carlos III. Work at Centro de Biologı´a Molecular ‘‘Severo Ochoa’’ (CISC-UAM) was supported by an institutional grant from Fundacio´n Ramo´n Areces. T.R-C. was supported by a contract from Comunidad Auto´noma de Madrid; S.O. and M.S-R were supported by a predoctoral fellowship from the Ministerio de Educacio´n y Ciencia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Immunoproteomic analysis of a Chikungunya poxvirus-based vaccine reveals high HLA class II immunoprevalence

BACKGROUND: Efficient adaptive antiviral cellular and humoral immune responses require previous recognition of viral antigenic peptides bound to human leukocyte antigen (HLA) class I and II molecules, which are exposed on the surface of infected and antigen presenting cells, respectively. The HLA-restricted immune response to Chikungunya virus (CHIKV), a mosquito-borne Alphavirus of the Togaviridae family responsible for severe chronic polyarthralgia and polyarthritis, is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a high-throughput mass spectrometry analysis of complex HLA-bound peptide pools isolated from large amounts of human cells infected with a vaccinia virus (VACV) recombinant expressing CHIKV structural proteins was carried out. Twelve viral ligands from the CHIKV polyprotein naturally presented by different HLA-A, -B, and -C class I, and HLA-DR and -DP class II molecules were identified. CONCLUSIONS/SIGNIFICANCE: The immunoprevalence of the HLA class II but not the HLA class I-restricted cellular immune response against the CHIKV structural polyprotein was greater than that against the VACV vector itself. In addition, most of the CHIKV HLA class I and II ligands detected by mass spectrometry are not conserved compared to its closely related O'nyong-nyong virus. These findings have clear implications for analysis of both cytotoxic and helper immune responses against CHIKV as well as for the future studies focused in the exacerbated T helper response linked to chronic musculoskeletal disorders in CHIKV patients.This work was supported by the Spanish Ministry of Economy grants SAF2014-58052 and “Acción Estratégica en Salud” 2018 to DL, SAF-2013-45232-R and SAF-2017-88089-R to ME, and by Israel Science Foundation, grant No. 1435/16 to AA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Efectos de un entrenamiento concurrente de fuerza y resistencia sobre carreras de media distancia

The aim of this study was to assess the effects of concurrent strength and endurance training on middle distance races in young athletes with moderate levels of performance. An organized work divided into different strength phases, also known as bloc periodization, was applied. Fifteen healthy and physically active university participants volunteered for the study. Individuals were randomly organized into two groups: resistance training group (RG: Age=21.3±2.3 years; Body Mass=66.8±1.9 kg; Height=172.0±2.3 cm; Fat Mass=10.8±1.1%) and strength training group (SG: Age=20.9±1.2 years; Body Mass=69.8±1.3 kg; Height=172.8±3.9 cm, Fat Mass=11.4±0.6%) who performed a strength protocol during 9 weeks (2 days/week). No significant differences were observed at the end of the nine weeks training. Both groups improved significantly their performance in the medium and long distance races, strength, resistance strength and their aerobic capacity (VO2max). Few changes were appreciable in the rest of the evaluated tests (60 and 300 meters). The greatest benefits were observed in the 2000 meters race. These improvements were detected from the first mesocycle and were especially evident at the end of the nine weeks. However, no significant differences were detected between groups (6.5±3.7 vs. 3.7±2.1 ml/kg/min; F=0.534; CI95%= -0.198, 5.932; p=0.65; ES=0.434). In conclusion, we can affirm that in this sample, incorporating strength training does not lead to greater benefits in comparison to just training the running performanceEl objetivo de este estudio fue evaluar los efectos del entrenamiento concurrente (fuerza y resistencia) sobre las carreras de media distancia en sujetos jóvenes de moderado nivel de rendimiento. Se aplicó un trabajo organizado en fases de diferente orientación de fuerza, lo que se conoce como periodización por bloques. Quin-ce universitarios sanos y físicamente activos participa-ron voluntariamente en el estudio. Fueron organizados aleatoriamente en dos grupos: uno que entrenaba solo resistencia (Grupo Resistencia: GR): Edad=21.3±2.3 años; Peso Corporal=66.8±1.9 kg; Estatura=172.0±2.3 cm; Gra-sa Corporal=10.8±1.1%) y otro (Grupo Fuerza-Resisten-cia: GFR): Edad=20.9±1.2 años; Peso Corporal=69.8±1.3 kg; Estatura=172.8±3.9 cm, Grasa Corporal=11.4±0.6%) al que se le añadió un protocolo de entrenamiento de fuerza de 9 semanas (2 días/semana) de duración. No se detectaron grandes diferencias en los cambios observa-dos en ambos grupos al final de las nueve semanas. Los dos grupos mejoraron significativamente su rendimien-to en las carreras de media y larga duración, la fuerza, la resistencia de fuerza y su capacidad aeróbica (VO2max). Los cambios fueron poco apreciables en el resto de las pruebas evaluadas (60 y 300 metros). Los mayores be-neficios se encontraron en la carrera de 2000 metros. Dichas mejoras se detectaron desde el primer mesociclo de entrenamiento y fueron especialmente evidentes al final de las nueve semanas. No obstante, no se detecta-ron diferencias relevantes entre ambos grupos (6.5±3.7 vs. 3.7±2.1 ml/kg/min; F=0.534; IC95%= -0.198, 5.932; p=0.65; ES=0.434). En conclusión, podemos afirmar que en esta muestra incorporar un trabajo de fuerza no con-lleva mayores beneficios que entrenar solo la carreraActividad Física y Deport