Whole inactivated virus influenza vaccine is superior to subunit vaccine in inducing immune responses and secretion of proinflammatory cytokines by DCs.
Whole inactivated virus influenza vaccine is superior to subunit vaccine in inducing immune responses and secretion of proinflammatory cytokines by DCs.
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DOI：
10.1111/j.1750-2659.2008.00038.x
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发表时间：
2008-03
影响因子：
4.4
通讯作者：
Huckriede A
中科院分区：
文献类型：
--
作者：
Geeraedts F;Bungener L;Pool J;ter Veer W;Wilschut J;Huckriede A
背景 用于预防流感病毒(再)感染不仅重要的是免疫反应的大小，而且其抗体亚类和T辅助细胞图谱的质量也是重要的。因此，迫切需要有关接种疫苗引起的免疫反应类型的信息。目的 本研究的目的是详细评估当前三种流感疫苗的免疫应答，并阐明决定这种免疫应答的疫苗特性。方法用全灭活病毒(WIV)、病毒小体(VS)和亚单位疫苗(SU)免疫 小鼠。随后感染活病毒后，检测血清抗体效价和Th细胞反应。体外研究疫苗对常规树突状细胞和浆细胞样树突状细胞产生细胞因子的影响。结果与结论 在BALB/c小鼠(Th2型倾向)和C57BL/6小鼠(Th1型倾向)诱导的血凝抑制滴度和病毒中和抗体滴度始终高于VS或SU。与VS和SU不同，WIV刺激抗体亚类IgG2a(Balb/c)和IgG2c(C57BL/6)的产生，这两种抗体被认为对病毒清除和产生干扰素-γ的T细胞的激活特别重要。与活病毒相似，WIV刺激常规树突状细胞产生致炎细胞因子，浆细胞样细胞产生干扰素-α，而VS和SU对上述两种细胞的细胞因子合成均无明显影响。我们的结论是，与VS或SU相比，WIV疫苗可产生所需的Th1应答，可能是通过诱导I型干扰素和其他促炎细胞因子实现的。
Background For protection against (re‐)infection by influenza virus not only the magnitude of the immune response but also its quality in terms of antibody subclass and T helper profile is important. Information about the type of immune response elicited by vaccination is therefore urgently needed. Objectives The aim of the study was to evaluate in detail the immune response elicited by three current influenza vaccine formulations and to shed light on vaccine characteristics which determine this response. Methods Mice were immunized with whole inactivated virus (WIV), virosomes (VS) or subunit vaccine (SU). Following subsequent infection with live virus, serum antibody titers and Th cell responses were measured. The effects of the vaccines on cytokine production by conventional and plasmacytoid dendritic cells were investigated in vitro. Results and conclusions In Balb/c mice (Th2 prone) as well as in C57Bl/6 mice (Th1 prone), WIV induced consistently higher hemagglutination‐inhibition titers and virus‐neutralizing antibody titers than VS or SU. In contrast to VS and SU, WIV stimulated the production of the antibody subclasses IgG2a (Balb/c) and IgG2c (C57BL/6), considered to be particularly important for viral clearance, and activation of IFN‐γ‐producing T cells. Similar to live virus, WIV stimulated the production of proinflammatory cytokines by conventional dendritic cells and IFN‐α by plasmacytoid cells, while VS and SU had little effect on cytokine synthesis by either cell type. We conclude that vaccination with WIV in contrast to VS or SU results in the desired Th1 response presumably by induction of type I interferon and other proinflammatory cytokines.