Eficacia y seguridad de la vacuna contra el dengue / Efficacy and safety of dengue vaccine

El dengue es un problema creciente para la salud pública mundial. En Argentina, los casos se han ido incrementado en los últimos años. La vacuna Dengvaxia (CYD-TDV) fue aprobada por la Agencia Nacional de Medicamentos, Alimentos y Tecnología (ANMAT) en 2017, y actualmente está indicada para personas entre los 9 y 45 años de edad que residan enzonas endémicas. A partir de la consulta de una paciente sobre la posibilidad de vacunarse contra el dengue, la autora se plantea la pertinencia de su indicación, teniendo en cuenta la eficacia y seguridad de la vacuna. Luego de una búsqueda rápida se encontró evidencia que señala que la vacuna contra el dengue CYD-TDV mostró poca eficacia en comparación con otras vacunas disponibles en el mercado, siendo más segura y eficaz en personas que ya han sido infectadas anteriormente por el virus del dengue (sujetos seropositivos). En cambio, se observó un aumento del riesgo de dengue grave en los infectados por vez primera tras la vacunación (sujetos seronegativos). Se concluye que la estrategia recomendada consiste en vacunar únicamente a las personas que hayan tenido infección por dengue con anterioridad, consistiendo en una buena práctica la toma de decisiones compartidas con cada paciente. (AU)

Dengue is a growing problem for global public health. In Argentina, cases have been increasing in recent years. The Dengvaxia vaccine (CYD-TDV) was approved by the National Agency for Medicines, Food and Technology in 2017, and it is currently indicated for people between 9 and 45 years of age who reside in endemic areas. Based on the consultation of a patient about the possibility of being vaccinated against dengue, the author considers the relevance of its indication, taking into account the efficacy and safety of the vaccine. After a quick search, evidence was found that indicates that the CYD-TDV dengue vaccine showed little efficacy compared to other vaccines available on the market, being safer and more effective in people who have already been previously infected by the dengue virus (seropositive subjects). In contrast, an increased risk of severe dengue was observed in those infected for the first time after vaccination (seronegative subjects). It is concluded that the recommended strategy consists of vaccinating only people who have had dengue infection before, making shared decisions with each patient a good practice. (AU)

Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles

Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs) are targets for dengue virus (DENV) and yellow fever virus (YF) replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681), a YF vaccine (YF17DD) and a chimeric YF17D/DENV2 vaccine in monocyte-derived DCs in vitro with regard to cell maturation, activation and cytokine production. Higher viral antigen positive cell frequencies were observed for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures exhibited dendritic cell activation and maturation molecules. CD38 expression on DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was decreased as compared to mock-stimulated cells, suggesting that a T helper 1 profile is favoured. Tumor necrosis factor (TNF)-α production in cell cultures was significantly higher in DENV2-infected cultures than in cultures infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN-α levels than DENV2. The differential cytokine production indicates that DENV2 results in TNF induction, which discriminates it from vaccine viruses that preferentially stimulate interferon expression. These differential response profiles may influence the pathogenic infection outcome.

Limited replication of yellow fever 17DD and 17D-Dengue recombinant viruses in rhesus monkeys

For the development of safe live attenuated flavivirus vaccines one of the main properties to be established is viral replication. We have used real-time reverse transcriptase-polymerase chain reaction and virus titration by plaque assay to determine the replication of yellow fever 17DD virus (YFV 17DD) and recombinant yellow fever 17D viruses expressing envelope proteins of dengue virus serotypes 2 and 4 (17D-DENV-2 and 17D-DENV-4). Serum samples from rhesus monkeys inoculated with YFV 17DD and 17D-DENV chimeras by intracerebral or subcutaneous route were used to determine and compare the viremia induced by these viruses. Viral load quantification in samples from monkeys inoculated by either route with YFV 17DD virus suggested a restricted capability of the virus to replicate reaching not more than 2.0 log10 PFU mL-1 or 3.29 log10 copies mL-1. Recombinant 17D-dengue viruses were shown by plaquing and real-time PCR to be as attenuated as YF 17DD virus with the highest mean peak titer of 1.97 log10 PFU mL-1 or 3.53 log10 copies mL-1. These data serve as a comparative basis for the characterization of other 17D-based live attenuated candidate vaccines against other diseases.

Uma das principais propriedades a serem estabelecidas para o desenvolvimento de vacinas seguras e atenuadas de flavivirus,é a taxa de replicação viral. Neste trabalho, aplicamos a metodologia de amplificação pela reação em cadeia da polimerase em tempo real e titulação viral por plaqueamento para determinação da replicação do vírus 17DD (FA 17DD) e recombinantes, expressando proteínas do envelope de dengue sorotipos 2 e 4 (17D-DENV-2 e 17D-DENV-4). As amostras de soros de macacos inoculados por via intracerebral ou subcutânea com FA 17DD ou 17D-DENV foram usadas para determinar e comparar a viremia induzida por estes vírus. A quantificação da carga viral em amostras de macacos inoculados por ambas as vias com FA 17DD sugere restrita capacidade de replicação com taxa não superior a 2,0 log10 PFU mL-1 ou 3,29 log10 cópias/mL-1. Os vírus recombinantes 17D-DENV mostraram-se tão atenuados quanto o vírus 17DD, tanto porRT-PCR em tempo real quanto por plaqueamento, com título médio máximo de 1,97 log10 PFU mL-1 ou 3,53 log10 cópias/mL-1. Estes dados servem como base comparativapara caracterização de outros vírus vivos atenuados, derivados do vírus 17D, candidatos a vacinas contra outras doenças.

Vacinas em desenvolvimento: estreptococo do grupo B, herpes-zóster, HIV, malária e dengue / Vaccines under development: group B streptococcus, herpes-zoster, HIV, malaria and dengue

OBJETIVOS: As vacinas contra o estreptococo B, o herpes-zóster, o HIV, a malária e a dengue, selecionadas por critérios de comercialização iminente ou devido a problemas específicos para sua obtenção, foram objeto de uma revisão sobre o estado atual do seu desenvolvimento. FONTE DOS DADOS:Foi realizada revisão da literatura através da MEDLINE no período de 1996 a 2006, sobre a epidemiologia e imunologia das doenças, analisando tanto os maiores problemas para a obtenção de uma vacina como o estado atual dos estudos, com ênfase para os que estavam em fase mais adiantada. SíNTESE DOS DADOS: Cada uma das cinco doenças escolhidas apresenta problemas específicos para o desenvolvimento de uma vacina. No entanto, a maioria deles já foi ou está em vias de ser resolvido, permitindo prever que uma vacina - ou vacinas - eficaz e segura estará disponível em futuro próximo. CONCLUSÕES:Apesar dos problemas enfrentados para o desenvolvimento dessas vacinas, os avanços da biologia molecular e da imunologia permitiram superar a maioria deles, abrindo a perspectiva para a obtenção de novas vacinas.