Rothman A L, Kanesa-thasan N, West K, Janus J, Saluzzo J F, Ennis F A
Center for Infectious Disease and Vaccine Research, Rm. S5-326, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Vaccine. 2001 Sep 14;19(32):4694-9. doi: 10.1016/s0264-410x(01)00236-5.
Development of a safe and immunogenic tetravalent dengue virus (DV) vaccine has been designated as a priority by the World Health Organization. We characterized the T cell response to DV induced by a candidate live attenuated tetravalent DV vaccine as part of a phase I study. Proliferation and cytotoxic T lymphocyte (CTL) responses to multiple DV serotypes were detected in six of six and four of four subjects studied, respectively. Proliferation responses 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 included serotype cross-reactive responses. Production of interferon-gamma, but not IL-4, was observed in response to DV stimulation. This candidate vaccine is immunogenic for both CD4+ and CD8+ T lymphocytes. However, T cell responses to the four DV serotypes were not equivalent, suggesting that the vaccine could be further optimized.
开发一种安全且具有免疫原性的四价登革热病毒(DV)疫苗已被世界卫生组织列为优先事项。作为一项I期研究的一部分,我们对一种候选的减毒活四价DV疫苗诱导的T细胞对DV的反应进行了表征。在研究的6名受试者中的6名以及4名受试者中的4名中,分别检测到了对多种DV血清型的增殖和细胞毒性T淋巴细胞(CTL)反应。对DV血清型1和3的增殖反应高于血清型2和4。对DV血清型2和3的CTL反应高于血清型1,并且包括血清型交叉反应。在对DV刺激的反应中观察到了干扰素-γ的产生,但未观察到IL-4的产生。这种候选疫苗对CD4 +和CD8 + T淋巴细胞均具有免疫原性。然而,T细胞对四种DV血清型的反应并不相同,这表明该疫苗可以进一步优化。