Dengue Mosaic Vaccines Enhance Cellular Immunity and Expand the Breadth of Neutralizing Antibody Against All Four Serotypes of Dengue Viruses in Mice
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fimmu-10-01429.pdf
Description
Published version
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2.51 MB
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Author(s)
Hou, Jue
Shrivastava, Shubham
Fraser, Christopher C.
Loo, Hooi Linn
Wong, Lan Hiong
Ho, Victor
Ooi, Eng Eong
Chen, Jianzhu
Date Issued
June 2019
Journal
Frontiers in Immunology
Publisher
Frontiers Research Foundation
Citation
Hou, Jue, Shubham Shrivastava, Christopher C. Fraser et al. "Dengue Mosaic Vaccines Enhance Cellular Immunity and Expand the Breadth of Neutralizing Antibody Against All Four Serotypes of Dengue Viruses in Mice." Frontiers in Immunology 10 (June 2019): Article 1429. © The Author(s). doi: 10.3389/fimmu.2019.01429
Version
Final published version
Abstract
An estimated 400 million people in the world are infected with any of the four types of dengue virus (DENV) annually. The only licensed dengue vaccine cannot effectively prevent infection with all of the four DENVs, especially in those immunologically naïve at baseline. In this study, we explored a mosaic vaccine approach, which utilizes an artificial recombinant sequence for each serotype to achieve maximum coverage of variant epitopes in the four DENVs. We determined the immunogenicity and cross-reactivity of DNA plasmids encoding individual mosaic sequences or the natural sequences in mice. We show that the mosaic vaccines, particularly those targeting DENV serotype 1 and 2, improved vaccine immunogenicity by increasing the percentage of antigen-specific IFNγ- or TNFα-secreting CD4 and CD8 T cells, and titers of neutralizing antibodies. The mosaic vaccine diversified and broadened anti-dengue T cell responses and cross-reactive neutralizing antibodies against all four serotypes. The mosaic vaccines also induced higher level of antigen-specific B cell responses. These results suggest that mosaic vaccines comprising of DENV serotype 1 and 2 variant epitopes could stimulate strong and broad immune responses against all four serotypes. Keywords: dengue viruses, mosaic vaccine, T cell responses, neutralizing antibodies, cross-reactivity
MIT Department
Massachusetts Institute of Technology. Department of Biology
Singapore-MIT Alliance in Research and Technology (SMART)
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.3389/fimmu.2019.01429
