Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques.
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 huma...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5919018?pdf=render |
| _version_ | 1818469569632665600 |
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| author | 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 Clarisse Lorin Marie-Pierre Malice Elena Caride Lucile Warter |
| author_facet | 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 Clarisse Lorin Marie-Pierre Malice Elena Caride Lucile Warter |
| author_sort | Maria Beatriz Borges |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T21:25:18Z |
| format | Article |
| id | doaj.art-be4fe456209a47ed8979b30afe367e49 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T21:25:18Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-be4fe456209a47ed8979b30afe367e492022-12-22T02:29:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01134e019631110.1371/journal.pone.0196311Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques.Maria Beatriz BorgesRenato Sergio MarchevskyYgara S MendesLuiz Gustavo MendesAna Claudia DuarteMichael CruzAna Maria Bispo de FilippisPedro Fernando C VasconcelosMarcos FreireAkira HommaSally MossmanEdith LepineYannick VanloubbeeckClarisse LorinMarie-Pierre MaliceElena CarideLucile WarterThe 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.http://europepmc.org/articles/PMC5919018?pdf=render |
| spellingShingle | 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 Clarisse Lorin Marie-Pierre Malice Elena Caride Lucile Warter Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques. PLoS ONE |
| title | Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques. |
| title_full | Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques. |
| title_fullStr | Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques. |
| title_full_unstemmed | Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques. |
| title_short | Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques. |
| title_sort | characterization of recent and minimally passaged brazilian dengue viruses inducing robust infection in rhesus macaques |
| url | http://europepmc.org/articles/PMC5919018?pdf=render |
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