A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa.

The 2014-2015 Ebola epidemic affected several African countries, claiming more than 11,000 lives and leaving thousands with ongoing sequelae. Safe and effective vaccines could prevent or limit future outbreaks. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSV-ZEBOV) vaccine has shown marked immunogenicity and efficacy in humans but is reactogenic at higher doses. To understand its effects, we examined plasma samples from 115 healthy volunteers from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo. Fifteen plasma chemokines/cytokines were assessed at baseline and on days 1, 2 to 3, and 7 after injection. Significant increases in monocyte-mediated MCP-1/CCL2, MIP-1β/CCL4, IL-6, TNF-α, IL-1Ra, and IL-10 occurred on day 1. A signature explaining 68% of cytokine/chemokine vaccine-response variability was identified. Its score was higher in HD versus LD vaccinees and was associated positively with vaccine viremia and negatively with cytopenia. It was higher in vaccinees with injection-site pain, fever, myalgia, chills, and headache; higher scores reflected increasing severity. In contrast, HD vaccinees who subsequently developed arthritis had lower day 1 scores than other HD vaccinees. Vaccine dose did not influence the signature despite its influence on specific outcomes. The Geneva-derived signature associated strongly (ρ = 0.97) with that of a cohort of 75 vaccinees from a parallel trial in Lambaréné, Gabon. Its score in Geneva HD vaccinees with subsequent arthritis was significantly lower than that in Lambaréné HD vaccinees, none of whom experienced arthritis. This signature, which reveals monocytes' critical role in rVSV-ZEBOV immunogenicity and safety across doses and continents, should prove useful in assessments of other vaccines

A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa

The 2014-2015 Ebola epidemic affected several African countries, claiming more than 11,000 lives and leaving thousands with ongoing sequelae. Safe and effective vaccines could prevent or limit future outbreaks. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSV-ZEBOV) vaccine has shown marked immunogenicity and efficacy in humans but is reactogenic at higher doses. To understand its effects, we examined plasma samples from 115 healthy volunteers from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo. Fifteen plasma chemokines/cytokines were assessed at baseline and on days 1, 2 to 3, and 7 after injection. Significant increases in monocyte-mediated MCP-1/CCL2, MIP-1b/CCL4, IL-6, TNF-A, IL-1Ra, and IL-10 occurred on day 1. A signature explaining 68% of cytokine/chemokine vaccine-response variabilitywas identified. Its scorewas higher inHD versus LD vaccinees and was associated positively with vaccine viremia and negatively with cytopenia. It was higher in vaccinees with injection-site pain, fever, myalgia, chills, and headache; higher scores reflected increasing severity. In contrast, HD vaccinees who subsequently developed arthritis had lower day 1 scores than other HD vaccinees. Vaccine dose did not influence the signature despite its influence on specific outcomes. The Geneva-derived signature associated strongly (r = 0.97) with that of a cohort of 75 vaccinees from a parallel trial in Lambaréné, Gabon. Its score in Geneva HD vaccinees with subsequent arthritis was significantly lower than that in Lambaréné HD vaccinees, none of whom experienced arthritis. This signature, which reveals monocytes' critical role in rVSV-ZEBOV immunogenicity and safety across doses and continents, should prove useful in assessments of other vaccines. © 2017 The Authors, some rights reserve

El poder de los gobernadores. Conceptualización y medición en los ejecutivos locales mexicanos

Mexican governors have had great capabilities for action, before and after the transition, although in different degrees. The literature holds measurements of the power of governors; however, most lack an abstract conceptualization or do not consider the influence that local executives have beyond the territory they govern. In this work we establish a conceptualization to identify what is the basis of the power of governors. Based on the above, we formulate the Governor's Power Index and a couple of typologies to capture and measure the power that local executives have in Mexico. Methodology: The research is based on the multilevel nature of the structuring of a concept. On the first level we establish an abstract conceptualization of a governor's power. In the second level we identify the constituent dimensions that point to the presence or absence of the concept. On the third level, we determine empirical indicators (based on the constituent dimensions) to identify the concept in reality. These indicators are the basis of the index and the typologies. Conclusions: The governor of the state of Mexico, for the year 2015, has greater capabilities with respect to the rest; the above, both in the general index and in the typologies built. He is very closely followed by Jalisco and Chiapas, although this is not constant, as it is in the state of Mexico. On the other hand, the local executive of the state of Morelos is the weakest and is closely followed by the one in Querétaro. Originality: The conceptual framework established allows the formulation of a quantitative instrument, which is practical in comparative research. With this conceptual basis, the development of typologies is also possible, which is useful for research that needs to delve into specific aspects of the power of local executives.Os governadores mexicanos têm tido grandes capacidades de ação antes e depois da transição, embora em diferentes graus. Na literatura, há medições do poder dos governadores, mas a maioria carece de uma conceituação abstrata ou não considera a influência que os executivos locais têm mais além do território que governam. Neste trabalho, estabelecemos uma conceituação para identificar o que fundamenta o poder dos governadores. Com base nisso, formulamos o Índice de Poder do Governador e algumas tipologias para capturar e dimensionar o poder que os executivos locais têm no México. Metodologia: Esta pesquisa está baseada na natureza multinível da conformação de um conceito. No primeiro nível, estabelecemos uma conceituação abstrata do poder do governador. No segundo nível, identificamos as dimensões constitutivas que nos indicam quando está presente o conceito e quando não. No terceiro nível, determinamos indicadores empíricos (com base nas dimensões constitutivas) para identificar o conceito na realidade. Esses indicadores são a base do índice e das tipologias. Conclusões: O governador do estado de México, em 2015, teve maiores capacidades a respeito dos demais, tanto no índice geral quanto nas tipologias construídas. Os de Jalisco e Chiapas não estão longe disso, embora isso não seja constante, como acontece no estado de México. Em compensação, o executivo local do estado de Morelos é o mais fraco, e o segue muito de perto o de Querétaro. Originalidade: O referente conceitual constituído permite a formulação de um instrumento quantitativo, o que é prático em pesquisas comparativas; com essa base conceitual, também é possível desenvolver tipologias; isso é útil para pesquisas que exijam aprofundar em aspectos específicos sobre o poder dos executivos locais.Los gobernadores mexicanos han tenido grandes capacidades de acción, antes y después de la transición, aunque en diferentes grados. En la literatura existen mediciones del poder de los gobernadores; no obstante, la mayoría carecen de una conceptualización abstracta o no toman en cuenta la influencia que los ejecutivos locales tienen más allá del territorio que gobiernan. En este trabajo establecemos una conceptualización para identificar qué fundamenta el poder de los gobernadores. Basándonos en lo anterior, formulamos el Índice de Poder del Gobernador y un par de tipologías para capturar y dimensionar el poder que tienen los ejecutivos locales en México. Metodología: La investigación está basada en la naturaleza multinivel de la conformación de un concepto. En el primer nivel establecemos una conceptualización abstracta del poder del gobernador. En el segundo nivel identificamos las dimensiones constitutivas que nos señalan cuando está presente el concepto y cuando no. En el tercer nivel, determinamos indicadores empíricos (basándonos en las dimensiones constitutivas) para identificar el concepto en la realidad. Esos indicadores son la base del índice y las tipologías. Conclusiones: El gobernador del estado de México, para el año 2015, tiene mayores capacidades respecto al resto; lo anterior, tanto en el índice general como en las tipologías construidas. Muy de cerca lo siguen Jalisco y Chiapas, aunque esto no es constante, como sí lo es en el estado de México. En contrapartida, el ejecutivo local del estado de Morelos es el más débil, y lo sigue muy de cerca el de Querétaro. Originalidad: El marco conceptual constituido permite la formulación de un instrumento cuantitativo, lo cual es práctico en investigaciones comparativas; con esta base conceptual también es posible el desarrollo de tipologías, esto es útil para investigaciones que requieren profundizar en aspectos específicos sobre el poder de los ejecutivos locales