Xiao Wenjun, Du Lanying, Liang Chao, Guan Jie, Jiang Shibo, Lustigman Sara, He Yuxian, Zhou Yusen
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology & Epidemiology, Beijing 100071, China.
Vaccine. 2008 Sep 15;26(39):5022-9. doi: 10.1016/j.vaccine.2008.07.028. Epub 2008 Aug 19.
Alum, the only adjuvant approved for clinical applications, can induce strong humoral (Th2) but weak cellular (Th1) immune responses. It is necessary to develop safe and effective adjuvants capable of inducing both humoral and cellular immune responses. We previously showed that activation-associated protein-1 (ASP-1) derived from Onchocerca volvulus has potent adjuvant activity. In this study, we have further evaluated the adjuvanticity of recombinant ASP-1 using a panel of recombinant proteins or synthetic peptide-based antigens, including ovalbumin (OVA), synthetic HIV peptide (HIV-p), recombinant HIV gp41 (rgp41) and HBV HBsAg, as well as three commercially available inactivated vaccines against haemorrhagic fever with renal syndrome (HFRS), Influenza and Rabies. Our results indicate that ASP-1 induced significantly higher IgG1 (Th2-associated) and IgG2a (Th1-associated) responses than alum adjuvant against OVA antigen, HIV-p, and rgp41. Consistently, it induced similar level of IgG1 responses as alum but higher level of IgG2a and IFN-gamma-producing T cell responses than alum adjuvant against HBsAg. Further, ASP-1 improved both IgG1 and IgG2a responses to three commercial inactivated vaccines when used separately or in combination. In conclusion, the recombinant ASP-1, unlike alum adjuvant, is able to induce both Th1 and Th2-associated humoral responses and Th1 cellular responses, suggesting that it can be further developed as a promising adjuvant for subunit-based and inactivated vaccines.
明矾是唯一被批准用于临床的佐剂,它能诱导强烈的体液(Th2)免疫反应,但细胞(Th1)免疫反应较弱。因此,开发能够诱导体液和细胞免疫反应的安全有效的佐剂很有必要。我们之前发现,盘尾丝虫的激活相关蛋白-1(ASP-1)具有强大的佐剂活性。在本研究中,我们使用一组重组蛋白或基于合成肽的抗原,包括卵清蛋白(OVA)、合成HIV肽(HIV-p)、重组HIV gp41(rgp41)和乙肝表面抗原(HBsAg),以及三种市售的肾综合征出血热(HFRS)、流感和狂犬病灭活疫苗,进一步评估了重组ASP-1的佐剂活性。我们的结果表明,与明矾佐剂相比,ASP-1针对OVA抗原、HIV-p和rgp41诱导的IgG1(与Th2相关)和IgG2a(与Th1相关)反应显著更高。同样,针对HBsAg,它诱导的IgG1反应水平与明矾相似,但IgG2a和产生IFN-γ的T细胞反应水平高于明矾佐剂。此外,ASP-1单独使用或联合使用时,均可增强对三种市售灭活疫苗的IgG1和IgG2a反应。总之,与明矾佐剂不同,重组ASP-1能够诱导Th1和Th2相关的体液反应以及Th1细胞反应,这表明它有望进一步开发成为基于亚单位和灭活疫苗的佐剂。