Adjuvanted H5N1 vaccine induces early CD4+ T cell response that predicts long-term persistence of protective antibody levels
Adjuvanted H5N1 vaccine induces early CD4+ T cell response that predicts long-term persistence of protective antibody levels
复制标题
DOI：
10.1073/pnas.0813390106
复制
发表时间：
2009-03-10
影响因子：
11.1
通讯作者：
Castellino, Flora
中科院分区：
文献类型：
--
作者：
Galli, Grazia;Medini, Duccio;Castellino, Flora
对疫苗接种的免疫反应在临床试验中得到检验。这个过程通常需要数年时间，尤其是在分析免疫记忆和持久性时。能够快速预测免疫反应的标记将非常有用，特别是在处理需要快速反应的新出现疾病（如禽流感）时。为了解决这个问题，我们在第1、22和202天为健康成人接种了普通或mf59佐剂的H5N1亚单位疫苗，并测试了细胞介导和抗体反应，直到第382天。只有MF59-H5N1疫苗能诱导高滴度的中和抗体、大量记忆型h5n1特异性B淋巴细胞和H5- cd4 (+) T细胞与漂移的H5广泛反应。CD4（+）应答由IL-2(+) ifn - γ (-) IL-13(-) T细胞主导。值得注意的是，1次剂量后可测量到的病毒特异性总CD4(+) T细胞频率增加3倍，准确地预测了加强免疫后中和抗体的增加及其在6个月后的维持。我们认为CD4(+) T细胞启动可能被用作大流行前疫苗免疫原性的早期预测因子。
Immune responses to vaccination are tested in clinical trials. This process usually requires years especially when immune memory and persistence are analyzed. Markers able to quickly predict the immune response would be very useful, particularly when dealing with emerging diseases that require a rapid response, such as avian influenza. To address this question we vaccinated healthy adults at days 1, 22, and 202 with plain or MF59-adjuvanted H5N1 subunit vaccines and tested both cell-mediated and antibody responses up to day 382. Only the MF59-H5N1 vaccine induced high titers of neutralizing antibodies, a large pool of memory H5N1-specific B lymphocytes, and H5-CD4(+) T cells broadly reactive with drifted H5. The CD4(+) response was dominated by IL-2(+) IFN-gamma(-) IL-13(-) T cells. Remarkably, a 3-fold increase in the frequency of virus-specific total CD4(+) T cells, measurable after 1 dose, accurately predicted the rise of neutralizing antibodies after booster immunization and their maintenance 6 months later. We suggest that CD4(+) T cell priming might be used as an early predictor of the immunogenicity of prepandemic vaccines.