Vacunas para SARS-CoV-2: diferentes estrategias de los desarrollos en curso / Vaccines for SARS-CoV-2: different strategies of ongoing developments

El objetivo de este artículo es proporcionar una guía que sirva para la interpretación y seguimiento de los esfuerzos que se están desarrollando en todo el mundo con el objetivo de obtener una vacuna que pueda generar inmunidad contra el nuevo coronavirus SARS-CoV-2 de 2019, el agente causante de la enfermedad por coronavirus denominada COVID-19. Cinco meses después de haber sido detectada la enfermedad, ya hay 102 vacunas en distintos estadios de desarrollo, registradas por la Organización Mundial de la Salud (OMS), correspondientes a 8 plataformas vacunales con diferentes estrategias, y todos los días aparecen nuevas. Esto representará un enorme desafío de organismos internacionales, para la evaluación, comparación y selección de aquellas que cumplan con los criterios regulatorios indispensables de seguridad y eficacia y que, por otro lado, puedan ser producidas en cantidades suficientes para abastecer la demanda mundial. (AU)

The objective of this article is to provide a guide to help the interpretation and monitoring the efforts that are being carried out worldwide to obtain a vaccine that will be able to generate immunity against the new 2019 SARS-CoV-2 coronavirus, the viral agent causes the disease named COVID-19. Five months after the disease was detected, there are already 102 vaccines at different stages of development, registered by World Health Organization (WHO), corresponding to 8 vaccination platforms base on different strategies, and every day new ones appear. This will represent a huge challenge for international organizations, to evaluate, compare and selects those that will meet the essential regulatory criteria of safety and efficacy and that, would be able to be produced in enough quantities to supply the worldwide demand. Key words: SARS-Cov-2 vaccine, vaccine platform, COVID-19 strategy, attenuated virus, viral vector, viral proteins, viral DNA, viral RNA, nucleic acids, viral like particles, WHO. (AU)

Impact of double-stranded RNA characteristics on the activation of human 2'-5'-oligoadenylate synthetase 2 (OAS2).

Human 2'-5' oligoadenylate synthetases (OAS) are a family of interferon-inducible proteins that, upon activation by double-stranded RNA, polymerize ATP into 2'-5' linked oligoadenylates. In this study, we probed the RNA cofactor specificity of the two smallest isozymes, OAS1 and OAS2. First, we developed a strategy for the expression and purification of recombinant human OAS2 from eukaryotic cells and quantified the activity of the enzyme relative to OAS1 in vitro. We then confirmed that both OAS2 domains, as opposed to only the domain containing the canonical catalytic aspartic acid triad, are required for enzymatic activity. Enzyme kinetics of both OAS1 and OAS2 in the presence of a variety of RNA binding partners enabled characterization of the maximum reaction velocity and apparent RNA-protein affinity of activating RNAs. While in this study OAS1 can be catalytically activated by dsRNA of any length greater than 19 bp, OAS2 showed a marked increase in activity with increasing dsRNA length with a minimum requirement of 35 bp. Interestingly, activation of OAS2 was also more efficient when the dsRNA contained 3'-overhangs, despite no significant impact on binding affinity. Highly structured viral RNAs that are established OAS1 activators were not able to activate OAS2 enzymatic activity based on the lack of extended stretches of dsRNA of greater than 35 bp. Together these results may highlight distinct subsets of biological RNAs to which different human OAS isozymes respond.

Microcefalia e Zika Vírus: características e associações / Microcephaly and Zika Virus: clinical features and associations / Microcefalia y Virus Zika: características y asociaciones

Objetivo: Discutir a associação entre microcefalia e a infecção materna por Zika Vírus. A microcefalia é o tamanho da cabeça menor do que o esperado em comparação com bebês do mesmo sexo e idade. Entre as causas conhecidas, estão as infecções congênitas. O aumento de casos entre outubro e novembro de 2015 no nordeste brasileiro, que coincidiu com a presença da circulação de novo vírus no país, em maio do mesmo ano, criou a hipótese de associação entre a microcefalia e a infecção materna durante a gravidez. O Zika Vírus é um arbovírus similar ao da Febre Amarela e da Dengue, transmitido principalmente através da picada do Aedes aegypti. A provável transmissão por relação sexual e transfusão de sangue, além de outros vetores como o Aedes albopictus e possivelmente até o pernilongo (Culex sp) aumentam a necessidade de cuidados preventivos em relação à infecção. O exame para detecção viral idealmente é realizado até o quinto dia após o início dos sintomas. Sorologias ainda não são amplamente disponíveis no Brasil. Métodos: Revisão narrativa da literatura. Conclusão: A associação entre casos de microcefalia e o Zika Vírus é embasada nos relatos de relação têmporo-espacial, padrão de alterações neurológicas associado a malformações congênitas, presença do RNA viral no líquido amniótico e nos tecidos de fetos. As respostas definitivas de causalidade serão possíveis após pesquisas e disponibilidade de exames laboratoriais. As evidências até agora apoiam fortemente esta hipótese e todas as medidas preventivas devem ser estimuladas.

Objective: To discuss the association between microcephaly and intrauterine infection by Zika virus. Microcephaly occurs when a child is born with a head smaller than expected when compared to babies of the same sex and age. Known causes of microcephaly include congenital infections. The increase in the number of microcephaly cases in Northeast Brazil between October and November 2015, which coincided with the emergence of Zika virus in the country in May of the same year, led to the hypothesis of an association between microcephaly and intrauterine Zika virus infection. Zika is an arbovirus that is closely related to yellow fever and dengue viruses. Aedes aegypti mosquitoes are the primary vector of transmission. Possible transmission through sexual contact and blood transfusion, as well as the implication of other vectors, such as Aedes albopictus and even Culex sp increases the need for preventive action. The test for viral detection is ideally performed before the 5th day following the onset of symptoms. Serology tests are not yet widely available in Brazil. Methods: We performed a narrative literature review. Conclusion: The hypothesis of an association between microcephaly and Zika virus is based on reports of spatial/temporal relationship, pattern of neurologic alterations associated with congenital malformations, and findings of viral RNA in amniotic fluid and fetal tissue. Definitive conclusions about the causality can only be reached after further research and availability of laboratory tests. The current evidence strongly supports the association between microcephaly and Zika infection, and all preventive measures must be stimulated.

Objetivo: Discutir las asociaciones entre microcefalia e infección materna por Virus Zika. La microcefalia es el tamaño de la cabeza menor de lo esperado en comparación con los bebés del mismo sexo y edad. Entre las causas conocidas están las infecciones congénitas. El aumento de casos entre octubre y noviembre de 2015 en el nordeste de Brasil, que coincidió con la presencia de la nueva circulación del virus en el país en mayo del mismo año, creó la hipótesis de asociación entre la microcefalia y la infección de la madre por Virus Zika durante el embarazo. El virus Zika es un arbovirus similar al dengue y la fiebre amarilla. El virus se transmite a través de la picadura del mosquito Aedes aegypti. La probable transmisión por vía sexual y por la transfusión de sangre - además de otros vectores como el Aedes albopictus y posiblemente el mosquito Culex sp - aumentan la necesidad de atención preventiva contra la infección. El cuadro clínico es benigno, autolimitado, caracterizado por erupción maculopapular asociado con otros síntomas tales como conjuntivitis, artralgia y la inflamación de las articulaciones. El examen para la detección del virus se realiza idealmente por el quinto día después de la aparición de los síntomas. Las pruebas serológicas no están ampliamente disponibles en Brasil. Métodos: Revisión de literatura. Conclusión: La asociación entre los casos de microcefalia y el virus Zika se basa en informes de patrón de relación temporo-espacial de los trastornos neurológicos asociados con malformaciones congénitas, el ARN viral presente en el líquido amniótico y tejidos de fetos. Las respuestas definitivas de causalidad serán posibles después de la investigación y la disponibilidad de pruebas de laboratorio. Hasta ahora, las evidencias apoyan firmemente esta hipótesis y todas las medidas preventivas deben ser estimuladas.

Caracterización intratípica de Poliovirus por la técnica de reacción en cadena de la polimerasa

Se introdujo la técnica de la reacción en cadena de la polimerasa para la caracterización intratípica de Poliovirus. Se usaron cebadores que sólo promueven la ampliación de las cepas vacunales de Sabin, comprobada por corrida electroforética de los productos de ADN amplificados (Sabin 1-97 pb, Sabin 2-71 pb, Sabin 3-44 pb) y cuya especificidad se verificó satisfactoriamente. Se estudiaron por esta técnica 23 cepas cubanas de Poliovirus aisladas e identificadas en el Laboratorio de Enterovirus del Instituto de Medicina Tropical "Pedro Kourí" de 1993 a 1994, y todas resultaron ser del tipo vacunal. Se observó cómo el Poliovirus vacunal de Sabin puede ser causa de meningoencefalitis viral como complicación neurológica más leve. Este estudio aportó una evidencia más a favor de la no circulación del Poliovirus salvaje en Cuba.

The polimerase chain reaction techniques was introduced for the intratypic characterization of Poliovirus. Primers were used only to promote the amplification of the Sabin vaccine strains proved by electrophoretic run of the amplified DNA products (Sabin 1 - 97 pb, Sabin 2 - 71 pb, Sabin 3 - 44 pb) and whose specificity was satisfactorily verified. 23 Cuban poliovirus strains isolated and identified at the Laboratory of Enterovirus of the "Pedro Kourí" Tropical Medicine Institute from 1993 to 1994 were studied by this technique. All of them were of the vaccine type. It was observed how the Sabin vaccine poliovirus may be the cause of viral meningoencephalitis as a milder neurological complication. Tghis study provided one more evidence about the non circulation of the wild poliovirus in Cuba.