Autor(es):
Borges, Maria Beatriz ; Marchevsky, Renato Sergio ; Mendes, Ygara S ; Mendes, Luiz Gustavo ; Duarte, Ana Claudia ; Cruz, Michael ; Filippis, Ana Maria Bispo de ; Vasconcelos, Pedro Fernando da Costa ; Freire, Marcos ; Homma, Akira ; Mossman, Sally ; Lepine, Edith ; Vanloubbeeck, Yannick ; Lorin, Clarisse ; Malice, Marie-Pierre ; Caride, Elena ; Warter, Lucile
Data: 2018
Origem: Oasisbr
Assunto(s): V?rus da Dengue / patogenicidade; Vacinas contra Dengue; Macaca mulatta / metabolismo; Sorotipagem / m?todos
Descrição
GlaxoSmithKline Biologicals S.A. (Rixensart, Belgium) under a Cooperative Research and Development Agreement with Fiocruz(Rio de Janeiro, Brazil). GlaxoSmithKline Biologicals S.A. was involved in the study design, data collection and analysis, decision to publish and preparation of the manuscript. PFCV was partially supported by MoH and CNPq (457664/2013-4 and 303999/ 2016-0)
Funda??o Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.
Funda??o Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.
Funda??o Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.
Funda??o Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.
Funda??o Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.
GSK. Rockville, Maryland, United States of America.
Funda??o Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Funda??o Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.
Funda??o Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.
GSK. Rockville, Maryland, United States of America.
GSK. Rockville, Maryland, United States of America.
GSK. Rixensart, Belgium.
GSK. Rixensart, Belgium.
GSK. Rixensart, Belgium.
Funda??o Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.
GSK. Rixensart, Belgium.
The macaque is widely accepted as a suitable model for preclinical characterization of dengue vaccine candidates. However, the only vaccine for which both preclinical and clinical efficacy results were reported so far showed efficacy levels that were substantially different between macaques and humans. We hypothesized that this model?s predictive capacity may be improved using recent and minimally passaged dengue virus isolates, and by assessing vaccine efficacy by characterizing not only the post-dengue virus challenge viremia/RNAemia but also the associated-cytokine profile. Ten recent and minimally passaged Brazilian clinical isolates from the four dengue virus serotypes were tested for their infectivity in rhesus macaques. For the strains showing robust replication capacity, the associated-changes in soluble mediator levels, and the elicited dengue virus-neutralizing antibody responses, were also characterized. Three isolates from dengue virus serotypes 1, 2 and 4 induced viremia of high magnitude and longer duration relative to previously reported viremia kinetics in this model, and robust dengue virus-neutralizing antibody responses. Consistent with observations in humans, increased MCP-1, IFN-? and VEGF-A levels, and transiently decreased IL-8 levels were detected after infection with the selected isolates. These results may contribute to establishing a dengue macaque model showing a higher predictability for vaccine efficacy in humans.
