The innate immune response following multivalent dengue vaccination and implications for protection against dengue challenge.

Understanding the immune response to dengue virus (DENV) is essential for developing a dengue vaccine that is protective against all 4 DENV serotypes. We evaluated the immune response after vaccination (live attenuated tetravalent dengue vaccine TV005 or trivalent admixture) and after challenge with DEN2Δ30 (Tonga/74) to better understand the importance of homotypic immunity in vaccine protection. Significant increases in IP-10 expression were observed following receipt of either the trivalent or tetravalent vaccine. After challenge, a large increase in IP-10 expression was observed in the placebo and trivalent admixture groups but not in the tetravalent vaccine group. MCP-1, IL-1RA, and MIP-1ß exhibited a similar pattern as IP-10. These results demonstrate protective effects of trivalent and tetravalent vaccines against DENV and suggest that the tetravalent vaccine has a better protective effect compared with the trivalent admixture. We also explored the postvaccination and postchallenge immune response differences between Black and White participants. White participants responded to vaccine differently than Black participants; Black participants receiving trivalent and tetravalent vaccines responded strongly and White participants responded only transiently in trivalent group. In response to challenge, White participants elicited a stronger response than Black participants. These results may explain why White participants may have a more vigorous DENV immune response than Black participants, as reported in literature.

The impact of host diet on Wolbachia titer in Drosophila.

While a number of studies have identified host factors that influence endosymbiont titer, little is known concerning environmental influences on titer. Here we examined nutrient impact on maternally transmitted Wolbachia endosymbionts in Drosophila. We demonstrate that Drosophila reared on sucrose- and yeast-enriched diets exhibit increased and reduced Wolbachia titers in oogenesis, respectively. The yeast-induced Wolbachia depletion is mediated in large part by the somatic TOR and insulin signaling pathways. Disrupting TORC1 with the small molecule rapamycin dramatically increases oocyte Wolbachia titer, whereas hyper-activating somatic TORC1 suppresses oocyte titer. Furthermore, genetic ablation of insulin-producing cells located in the Drosophila brain abolished the yeast impact on oocyte titer. Exposure to yeast-enriched diets altered Wolbachia nucleoid morphology in oogenesis. Furthermore, dietary yeast increased somatic Wolbachia titer overall, though not in the central nervous system. These findings highlight the interactions between Wolbachia and germline cells as strongly nutrient-sensitive, and implicate conserved host signaling pathways by which nutrients influence Wolbachia titer.