HLA restricted CD8+ T cell responses following vaccination with monovalent and tetravalent dengue live attenuated vaccines (VAC7P.983)

Abstract

Abstract The frequency of infection with any of the four dengue viruses (DENV 1-4) has increased dramatically in the last few decades, and the lack of a vaccine has led to significant morbidity and mortality worldwide. Correlates of protection from severe dengue disease and vaccine efficacy have not yet been established. A recent comprehensive analysis of T cell response against dengue virus suggested an HLA-linked protective role for CD8+ T cells, predominantly targeting the non-structural (NS) proteins. Here, we characterize for the first time CD8+ T cell responses after experimental vaccination and compare it to responses observed in natural infection with dengue virus (DENV). We have collected full blood donations from study participants receiving a dose of the monovalent or tetravalent live attenuated DENV vaccine (DLAV) developed by the NIH. CD8+ T cell responses in vaccinees were readily detectable with magnitude and breadth similar to natural dengue infection. Interestingly, while broad responses to all proteins have been observed after monovalent vaccination we have observed a dramatic focus of the T cell responses to the highly conserved proteins NS3 and NS5. Epitopes from these proteins are highly represented in a vast variety of field isolates and are able to elicit multifunctional T cell responses. Detailed knowledge of the T cell response may contribute to identify robust correlates of protection in natural immunity and vaccination against DENV.