The innate immune response following multivalent dengue vaccination and implications for protection against dengue challenge
Ruixue Hou, Lewis E. Tomalin, Jessica Pintado Silva, Seunghee Kim-Schulze, Stephen S. Whitehead, Ana Fernandez-Sesma, Anna P. Durbin, Mayte Suárez-Fariñas
Ruixue Hou, Lewis E. Tomalin, Jessica Pintado Silva, Seunghee Kim-Schulze, Stephen S. Whitehead, Ana Fernandez-Sesma, Anna P. Durbin, Mayte Suárez-Fariñas
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Research Article Immunology Infectious disease

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

Abstract

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-1β 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.

Authors

Ruixue Hou, Lewis E. Tomalin, Jessica Pintado Silva, Seunghee Kim-Schulze, Stephen S. Whitehead, Ana Fernandez-Sesma, Anna P. Durbin, Mayte Suárez-Fariñas

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Figure 2

Cytokine levels are differentially expressed after vaccination and after challenge.

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Cytokine levels are differentially expressed after vaccination and after...
(A) Heatmap showing the average expression of proteins with significant changes (FDR < 0.05) of cytokine levels over time (day 8 vs. day 0, day 21 vs. day 0, day 188 vs. day 0, day 201 vs. day 0, day 188 vs. day 180, day 201 vs. day 180) or significant differences between group (tetravalent vs. placebo, trivalent vs. placebo). Dendrograms were from hierarchical clustering applied to proteins (y axis). The color of the heatmap in each row is based on the Z score values calculated by centering and scaling the data by SD using the formula (X – m)/SD, where X denotes individual values, and m represents the mean of the row. Plc, placebo; TV, tetravalent. (B) Plots showing estimated least-squares mean and SEM for IP-10, IL-1RA, MIP-1b, and MCP-1. Symbols right above the CI bars represent significance of the changes from day 8 or day 21 vs. day 0 as well as day 188 or day 201 vs. day 180 for each vaccine group (placebo, gray; trivalent admixture, red; and tetravalent vaccine, blue). Mixed-effects model in the limma framework was used, with age, sex, and race as fixed effects covariates as well as interaction time by vaccine group and a random intercept for each participant. Symbols on the top represent significance of the comparison between intervention groups (trivalent vs. placebo [purple] and tetravalent vs. placebo [blue]). The adjusted P value is shown as +FDR < 0.1, *FDR < 0.05, **FDR < 0.01, ***FDR < 0.001.