Liposome-based polymer complex as a novel adjuvant: enhancement of specific antibody production and isotype switch.

Liposome-based polymer complex as a novel adjuvant: enhancement of specific antibody production and isotype switch.
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DOI:
10.2147/ijn.s28097
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发表时间:
2012
影响因子:
8
通讯作者:
Liao KW
Liao KW
中科院分区:
医学2区
文献类型:
--
作者:
Chen CH;Lin YL;Liu YK;He PJ;Lin CM;Chiu YH;Wu CJ;Cheng TL;Liu SJ;Liao KW

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接种疫苗的目的是诱导针对病原体的适当免疫力。抗体介导的免疫对于预防许多病毒性疾病至关重要,尽管越来越明显的是,协调的多功能免疫应答导致最有效的防御。特异性抗体(Ab)同种型在保护体内不同部位免受病原体入侵方面更有效。例如,与其他Ab同种型相比,免疫球蛋白(IG)A在粘膜区域提供更多的保护。在这项研究中,我们开发了一种阳离子脂质聚合物(脂质体-聚乙二醇-聚乙烯亚胺复合物[LPPC])佐剂,它可以将抗原或免疫调节剂强烈吸附到其表面,以增强或转换免疫反应。结果表明,LPPC增强小鼠吞噬细胞的摄取能力、表面标志物表达、促炎细胞因子释放和抗原呈递。与弗氏佐剂相反,LPPC在体内优先激活针对抗原的Th 1免疫。与脂多糖或CpG寡脱氧核苷酸,LPPC显着提高伊加或IgG 2A的总IG的比例,即使在主机已开发的Th 2免疫和高IgG 1血清滴度。总之,结果表明LPPC佐剂不仅增加抗原的免疫原性,而且通过与免疫调节剂组合调节宿主免疫以产生适当的Ab同种型。
The aim of vaccination is to induce appropriate immunity against pathogens. Antibody-mediated immunity is critical for protection against many virus diseases, although it is becoming more evident that coordinated, multifunctional immune responses lead to the most effective defense. Specific antibody (Ab) isotypes are more efficient at protecting against pathogen invasion in different locations in the body. For example, compared to other Ab isotypes, immunoglobulin (Ig) A provides more protection at mucosal areas. In this study, we developed a cationic lipopolymer (liposome-polyethylene glycol-polyethyleneimine complex [LPPC]) adjuvant that strongly adsorbs antigens or immunomodulators onto its surface to enhance or switch immune responses. The results demonstrate that LPPC enhances uptake ability, surface marker expression, proinflammatory cytokine release, and antigen presentation in mouse phagocytes. In contrast to Freund’s adjuvant, LPPC preferentially activates Th1- immunity against antigens in vivo. With lipopolysaccharides or CpG oligodeoxynucleotides, LPPC dramatically enhances the IgA or IgG2A proportion of total Ig, even in hosts that have developed Th2 immunities and high IgG1 serum titers. Taken together, the results demonstrate that the LPPC adjuvant not only increases the immunogenicity of antigens but also modulates host immunity to produce an appropriate Ab isotype by combining with immunomodulators.