Guy Bruno, Chanthavanich Pornthep, Gimenez Sophie, Sirivichayakul Chukiat, Sabchareon Arunee, Begue Sarah, Yoksan Sutee, Luxemburger Christine, Lang Jean
R&D Department, Aventis Pasteur, Lyon, France.
Vaccine. 2004 Sep 9;22(27-28):3563-74. doi: 10.1016/j.vaccine.2004.03.042.
Sera from Thai children immunized with a live-attenuated tetravalent dengue virus vaccine or from naturally infected age-matched site-control subjects were examined for immune enhancement capacity by a highly reproducible flow cytometric assay in Fc receptor-bearing K562 human cells. None of the sera under study corresponded to cases of severe dengue disease. In parallel assays employing each dengue virus serotype, we found no or only minimal antibody-dependent enhancement (ADE) when sera from vaccinated or control subjects were used at a low serum dilution [1/12] that approximated the in vivo condition. Among sera that exhibited homotypic neutralizing antibody activity against DV1-3, the level correlated with absence of ADE or infection with the respective serotype. Similarly, a broad heterotypic neutralizing antibody response that included all four serotypes was linked to complete absence of K562 cell infection. In contrast, at higher serum dilutions a correlation between breadth of antibody response and heightened immune enhancement emerged, a pattern identical to that observed among control subjects. These findings support the use of live dengue vaccines and protocols that induce broad serotype-specific neutralizing antibody responses, but they also suggest that clinically relevant immune enhancement may not be likely if this is not uniformly achieved after the first immunization.
采用高度可重复的流式细胞术检测法，在表达Fc受体的K562人细胞中，对接种减毒活四价登革病毒疫苗的泰国儿童血清或年龄匹配的自然感染对照受试者血清的免疫增强能力进行了检测。所研究的血清均未对应严重登革热疾病病例。在使用每种登革病毒血清型的平行检测中，当以接近体内情况的低血清稀释度[1/12]使用接种疫苗或对照受试者的血清时，我们未发现或仅发现极少的抗体依赖性增强（ADE）。在对DV1 - 3表现出同型中和抗体活性的血清中，该水平与不存在ADE或感染相应血清型相关。同样，包含所有四种血清型的广泛异型中和抗体反应与K562细胞感染完全不存在相关。相比之下，在更高的血清稀释度下，抗体反应广度与增强的免疫增强之间出现了相关性，这一模式与在对照受试者中观察到的相同。这些发现支持使用能诱导广泛血清型特异性中和抗体反应的活登革疫苗和方案，但它们也表明，如果首次免疫后不能一致地实现这一点，临床相关的免疫增强可能不太可能发生。
