OVA-bound nanoparticles induce OVA-specific IgG1, IgG2a, and IgG2b responses with low IgE synthesis.
OVA-bound nanoparticles induce OVA-specific IgG1, IgG2a, and IgG2b responses with low IgE synthesis.
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DOI：
10.1016/j.vaccine.2014.08.059
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发表时间：
2014-10
期刊：
影响因子：
5.5
通讯作者：
N. Yanase;H. Toyota;Kikumi Hata;S. Yagyu;Takahiro Seki;M. Harada;Y. Kato;J. Mizuguchi
中科院分区：
文献类型：
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作者：
N. Yanase;H. Toyota;Kikumi Hata;S. Yagyu;Takahiro Seki;M. Harada;Y. Kato;J. Mizuguchi
迫切需要一种新的疫苗，能够刺激免疫反应，而不会产生不必要的毒性，包括IgE升高。我们检测了平均直径为110 nm的纳米颗粒(OVA-NPs)表面的抗原卵白蛋白(OVA)是否可以作为免疫佐剂。当用OVA-NPs免疫BALB/c小鼠时，它们产生了足够水平的OVA特异性IgG1抗体应答，而IgE合成水平较低，代表了辅助性T(Th)2介导的体液免疫。OVA-NPs二次免疫也可诱导OVA特异性的IgG2a和IgG2b反应(即Th1免疫)。正如预期的那样，明矾中的OVA免疫刺激了体液免疫反应，包括IgG1和IgE抗体，仅有低水平的IgG2a/IgG2b抗体。来自OVA-NPs组小鼠的CD4+T细胞产生大量的IL-21和IL-4，与OVA-明矾组相当。接受OVA-NPs免疫的B细胞和OVA明胶免疫的T细胞的照射小鼠，在OVA-NPs刺激后，相对于OVA明胶免疫的B细胞和T细胞，抗OVA IgG2b反应增强。此外，当卵清蛋白纳米粒免疫B细胞时，B细胞与抗CD40单抗、IL-4、IL-21或脂多糖+转化生长因子-β共同培养时，均可产生卵清蛋白特异性的IgG1或IgG2b抗体反应，提示卵泡蛋白纳米粒免疫可调节B细胞产生IgG1IgG2b反应。因此，OVA-NPs可能对B细胞起到佐剂作用，是一种潜在的疫苗，可同时产生低IgE合成的IgG1和IgG2a/IgG2b抗体应答。
There is an urgent requirement for a novel vaccine that can stimulate immune responses without unwanted toxicity, including IgE elevation. We examined whether antigen ovalbumin (OVA) conjugated to the surface of nanoparticles (NPs) (OVA-NPs) with average diameter of 110 nm would serve as an immune adjuvant. When BALB/c mice were immunized with OVA-NPs, they developed sufficient levels of OVA-specific IgG1 antibody responses with low levels of IgE synthesis, representing helper T (Th)2-mediated humoral immunity. OVA-specific IgG2a and IgG2b responses (i.e., Th1-mediated immunity) were also induced by secondary immunization with OVA-NPs. As expected, immunization with OVA in alum (OVA-alum) stimulated humoral immune responses, including IgG1 and IgE antibodies, with only low levels of IgG2a/IgG2b antibodies. CD4-positive T cells from mice primed with OVA-NPs produced substantial levels of IL-21 and IL-4, comparable to those from OVA-alum group. The irradiated mice receiving OVA-NPs-primed B cells together with OVA-alum-primed T cells exhibited enhanced anti-OVA IgG2b responses relative to OVA-alum-primed B cells and T cells following stimulation with OVA-NPs. Moreover, when OVA-NPs-primed, but not OVA-alum-primed, B cells were cultured in the presence of anti-CD40 monoclonal antibody, IL-4, and IL-21, or LPS plus TGF-βin vitro, OVA-specific IgG1 or IgG2b antibody responses were elicited, suggesting that immunization with OVA-NPs modulates B cells to generate IgG1 and IgG2b responses. Thus, OVA-NPs might exert their adjuvant action on B cells, and they represent a promising potential vaccine for generating both IgG1 and IgG2a/IgG2b antibody responses with low IgE synthesis.