SEROTYPE-SPECIFIC TH1 RESPONSES IN RECIPIENTS OF TWO DOSES OF CANDIDATE LIVE-ATTENUATED DENGUE VIRUS VACCINES

As part of a larger vaccine study, peripheral blood mononuclear cells (PBMC) were collected from volunteers for analysis of vaccine-induced T cell responses. The PBMC were re-stimulated in vitro with live dengue virus and assayed for T(H)1 or T(H)2 memory cell responses. Re-stimulated PBMC from the volunteers predominantly secreted interferon-gamma. Little interleukin-4 (IL-4) or IL-10 secretion was detected, indicating a T(H)1 type of T cell response. The interferon-gamma response was primarily serotype-specific with some serotype cross-reactivity. T cell depletion studies showed that the interferon-gamma was being secreted by CD4+ T lymphocytes and/or by cells other than CD8+ T lymphocytes that were being stimulated by the CD4+ T lymphocytes. CD3+ or CD8+ T cell depletion showed that granzyme B mRNA expression correlated with the presence of CD4+ T lymphocytes. However, depletion of CD4+ T cells after four days of stimulation indicated that the granzyme B mRNA was produced by cells in culture other than lymphocytes. In summary, an antigen-specific T(H)1 type T cell response was seen as a response to vaccination using live attenuated dengue virus.