[Source: PLoS One, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques
Maria Beatriz Borges, Renato Sergio Marchevsky, Ygara S. Mendes, Luiz Gustavo Mendes, Ana Claudia Duarte, Michael Cruz, Ana Maria Bispo de Filippis, Pedro Fernando C. Vasconcelos, Marcos Freire, Akira Homma, Sally Mossman, Edith Lepine, Yannick Vanloubbeeck, [ … ], Lucile Warter
Published: April 25, 2018 / DOI: https://doi.org/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.
Citation: Borges MB, Marchevsky RS, Mendes YS, Mendes LG, Duarte AC, Cruz M, et al. (2018) Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques. PLoS ONE 13(4): e0196311. https://doi.org/10.1371/journal.pone.0196311
Editor: Pierre Roques, CEA, FRANCE
Received: January 10, 2018; Accepted: April 10, 2018; Published: April 25, 2018
Copyright: © 2018 Borges et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: This work was funded by 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) grants.
Competing interests: The authors declare the following conflicts: MC, SM, YV, CL and LW are employees of the GSK group of companies. EL was an employee of the GSK group of companies at the time of the study. MPM is a freelancer doing business for GSK. SM, YV, CL and LW report owning shares and/or restricted shares in GSK. MBB, RSM, YSM, LGM, ACD, MF, AH and EC are employees of Fiocruz which was contracted by GSK in the context of this study. The other authors declare no conflict of interest. These do not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.
Keywords: Dengue Fever; Vaccines; Animal Models.