Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques

• Published in: PloS one Vol. 13; no. 4; p. e0196311
• Main Authors: Borges, Maria Beatriz, Marchevsky, Renato Sergio, Mendes, Ygara S, Mendes, Luiz Gustavo, Duarte, Ana Claudia, Cruz, Michael, de Filippis, Ana Maria Bispo, Vasconcelos, Pedro Fernando C, Freire, Marcos, Homma, Akira, Mossman, Sally, Lepine, Edith, Vanloubbeeck, Yannick, Lorin, Clarisse, Malice, Marie-Pierre, Caride, Elena, Warter, Lucile
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.04.2018; Public Library of Science (PLoS)
• Subjects: Animal research models; Biology and life sciences; Cell culture; Clinical isolates; Cytokines; Dengue; Dengue fever; Dengue virus; Development and progression; Effectiveness; Gene expression; Genetic aspects; Growth factors; Health aspects; Infections; Infectivity; Interleukin 8; Kinetics; Mathematical models; Medical research; Medicine and Health Sciences; Monocyte chemoattractant protein 1; Neutralizing; Proteins; Research and Analysis Methods; Robustness; Serotypes; Tumor necrosis factor-TNF; Vaccine efficacy; Vaccines; Vascular endothelial growth factor; Vector-borne diseases; Viral diseases; Viremia; Viruses; γ-Interferon; Brazil; Rio de Janeiro Brazil; Belgium; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0196311

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-γ 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.