Shen Erxia, Li Li, Li Lietao, Feng Lianqiang, Lu Lin, Yao Ziliang, Lin Haixiang, Wu Changyou
Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Cell Mol Immunol. 2007 Apr;4(2):113-20.
An adjuvant is usually used to enhance the immune response induced by vaccines. The choice of adjuvant or immune enhancer determines the effectiveness of the immune response. Currently, aluminium (Alum, a generic term for salts of aluminium) is the only FDA-approved adjuvant. Alum predominantly induces the differentiation of Th2 cells and thus mediates an antibody immune response. Therefore, there is an urgent need for new adjuvants that enhance not only humoral but also cellular immune responses. In the present study, we demonstrates that PIKA (a stabilized dsRNA) as an adjuvant directly induces the activation and the proliferation of both B and NK cells in vitro. Injection of PIKA into mice results in the production of cytokines in vivo. In addition, the study demonstrates that PIKA promotes the maturation of bone marrow-derived dendritic cells (BMDCs) including up-regulation of the co-stimulatory molecules CD80, CD86 and CD40, and the induction of cytokines such as IL-12p70, IL-12p40 and IL-6. Importantly, after immunization of mice with HBsAg plus PIKA, the presence of PIKA enhances the titers of HBsAg-specific IgG and HBsAg-specific IFN-gamma production. These results demonstrate that PIKA as an adjuvant can promote both humoral and cellular immune responses. These might have an implication in applying PIKA as an adjuvant to be used in the design and development of both therapeutic and preventive vaccines, and used in the clinical study.
佐剂通常用于增强疫苗诱导的免疫反应。佐剂或免疫增强剂的选择决定了免疫反应的有效性。目前，铝（明矾，铝盐的通用术语）是唯一获得美国食品药品监督管理局（FDA）批准的佐剂。明矾主要诱导Th2细胞分化，从而介导抗体免疫反应。因此，迫切需要不仅能增强体液免疫反应还能增强细胞免疫反应的新型佐剂。在本研究中，我们证明了PIKA（一种稳定的双链RNA）作为佐剂可在体外直接诱导B细胞和NK细胞的激活与增殖。将PIKA注射到小鼠体内会在体内产生细胞因子。此外，该研究表明PIKA可促进骨髓来源的树突状细胞（BMDCs）的成熟，包括共刺激分子CD80、CD86和CD40的上调，以及细胞因子如IL-12p70、IL-12p40和IL-6的诱导。重要的是，用乙肝表面抗原（HBsAg）加PIKA免疫小鼠后，PIKA的存在可提高HBsAg特异性IgG的滴度以及HBsAg特异性干扰素-γ的产生。这些结果表明，PIKA作为佐剂可促进体液免疫和细胞免疫反应。这可能对将PIKA用作佐剂应用于治疗性和预防性疫苗的设计与开发以及临床研究具有启示意义。
