A novel dengue NS3 epitope that induces robust cross-reactive memory CD8 T-cell responses to both dengue and Zika viruses
Jaturong Sewatanon1, John Sidney2, Rama Akondy3, 4, Alessandro Sette2, Rafi Ahmed3, 4
1Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 Thailand; 2Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037 USA; 3Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322 USA; 4Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322 USA
Thailand is dengue endemic country with predicted 80,000-100,000 cases in 2017. This is 22-37% higher than the amount of reported cases in 2016. Although dengue vaccine (Dengvaxia®) has been approved in Thailand, the efficacy of this vaccine is low in children younger than 9 years old (44%) and varies against different serotypes. Therefore, more effective vaccines that induce protective immune responses against dengue infections are still in need. Optimal T-cell responses during dengue infection could contribute to efficient lysis of infected cells, leading to protective immunity. Recently, we have identified a novel dengue non-structural protein 3 epitope (NS3296-304) that induced robust proliferation of interferon gamma (IFNγ)-producing CD8 T cells in peripheral blood mononuclear cells from a Thai healthy individual who has been infected with dengue virus but never had dengue illness. This suggests that these proliferated CD8 T cells are dengue-specific memory cells that robustly respond upon dengue virus infections. Moreover, this dengue NS3296-304 epitope was highly conserved among flaviviruses and bound to human leukocyte antigen HLA-B*38:02 that has allele frequency approximately 3% in Thai population. We also found that these dengue-specific memory CD8 T cells from this person with HLA-B*38:02 proliferated and produced multiple cytokines upon stimulation in vitro with analogous NS3 epitope of Zika virus. Our findings suggest that incorporating this NS3 epitope into a vaccine could be an appealing strategy to induce protective immunity to both dengue and Zika virus infections.