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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

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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 8

Cytokine expression and vaccination response.

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Cytokine expression and vaccination response.
(A) Bar plots showing the ...
(A) Bar plots showing the percentage of nonresponders and responders to vaccines in each vaccine group. (B) Box plots showing the maximum viremia load after challenge in each vaccine group. (C) Line plots showing the mean expression of 2 cytokines, RANTES and VEGF, over time from day 0 to day 180. There was suggestive evidence (P < 0.05) that RANTES at day 0 and change of VEGF from day 8 to day 21 were associated with response to vaccination over time. Linear model was used, with age, sex, and race as covariates. (D) Receiver operating characteristics (ROC) curves for predicting vaccination response with different cytokines and time points. Cytokines and time points used as predictors are indicated. AUC (95% CI) achieved by each predictor is also shown. Linear model was used, with age, sex, and race as covariates.

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ISSN 2379-3708

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