Induction of T lymphocyte responses to dengue virus by a candidate tetravalent live attenuated dengue virus vaccine

Development of a safe and immunogenic tetravalent dengue virus DV vaccine h as been designated as a priority by the World Health Organization. We chara cterized the T cell response to DV induced by a candidate live attenuated t etravalent DV vaccine as part of a phase I study. Proliferation and cytotox ic T lymphocyte (CTL) responses to multiple DV serotypes were detected in s ix of six and four of four subjects studied, respectively. Proliferation re sponses were higher to DV serotypes 1 and 3 than to serotypes 2 and 4. CTL responses were higher to DV serotypes 2 and 3 than to serotype 1, and inclu ded serotype cross-reactive responses. Production of interferon-gamma, but not IL-4, was observed in response to DV stimulation. This candidate vaccin e is immunogenic for both CD4 + and C138 + T lymphocytes. However, T cell r esponses to the four DV serotypes were not equivalent, suggesting that the vaccine could be further optimized. (C) 2001 Elsevier Science Ltd. All righ ts reserved.