Journal article
Patterns of Cellular Immunity Associated with Experimental Infection with rDEN2Δ30 (Tonga/74) Support Its Suitability as a Human Dengue Virus Challenge Strain
Journal of Virology, Vol.91(8)
2017
Abstract
A deletion variant of the dengue virus (DENV) serotype 2 (DENV2) Tonga/74 strain lacking 30 nucleotides from its 3′ untranslated region (rDEN2Δ30) has previously been established for use in a controlled human DENV challenge model. To evaluate if this model is appropriate for the derivation of correlates of protection for DENV vaccines on the basis of cellular immunity, we wanted to compare the cellular immune response to this challenge strain to the response induced by natural infection. To achieve this, we predicted HLA class I- and class II-restricted peptides from rDEN2Δ30 and used them in a gamma interferon enzyme-linked immunosorbent spot assay to interrogate CD8+ and CD4+ T cell responses in healthy volunteers infected with rDEN2Δ30. At the level of CD8 responses, vigorous ex vivo responses were detected in approximately 80% of donors. These responses were similar in terms of the magnitude and the numbers of epitopes recognized to the responses previously observed in peripheral blood mononuclear cells from donors from regions where DENV is hyperendemic. The similarity extended to the immunodominance hierarchy of the DENV nonstructural proteins, with NS3, NS5, and NS1 being dominant in both donor cohorts. At the CD4 level, the responses to rDEN2Δ30 vaccination were less vigorous than those to natural DENV infection and were more focused on nonstructural proteins. The epitopes recognized following rDEN2Δ30 infection and natural infection were largely overlapping for both the CD8 (100%) and CD4 (85%) responses. Finally, rDEN2Δ30 induced stronger CD8 responses than other, more attenuated DENV isolates.
Details
- Title
- Patterns of Cellular Immunity Associated with Experimental Infection with rDEN2Δ30 (Tonga/74) Support Its Suitability as a Human Dengue Virus Challenge Strain
- Authors/Creators
- A. Grifoni (Author/Creator) - La Jolla Institute for ImmunologyM. Angelo (Author/Creator) - La Jolla Institute for ImmunologyJ. Sidney (Author/Creator) - La Jolla Institute for ImmunologyS. Paul (Author/Creator) - La Jolla Institute for ImmunologyBjoern Peters (Author/Creator) - La Jolla Institute for ImmunologyA.D. de Silva (Author/Creator)E. Phillips (Author/Creator) - Vanderbilt UniversityS. Mallal (Author/Creator) - Vanderbilt UniversityS.A. Diehl (Author/Creator) - University of VermontJ. Botten (Author/Creator) - University of VermontJ. Boyson (Author/Creator) - University of VermontB.D. Kirkpatrick (Author/Creator) - University of VermontS.S. Whitehead (Author/Creator) - National Institute of Allergy and Infectious DiseasesA.P. Durbin (Author/Creator) - Bloomberg (United States)A. Sette (Author/Creator) - La Jolla Institute for ImmunologyD. Weiskopf (Author/Creator) - La Jolla Institute for ImmunologyA. García-Sastre (Author/Creator)
- Publication Details
- Journal of Virology, Vol.91(8)
- Publisher
- American Society for Microbiology
- Identifiers
- 991005542973107891
- Copyright
- © 2017 American Society for Microbiology
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- 1.228.200 Mosquito-borne Viruses
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