Bracho Gustavo, Zayas Caridad, Wang Lina, Coppel Ross, Pérez Oliver, Petrovsky Nikolai
Department of Immunology, Finlay Institute, Havana City, Cuba.
Malar J. 2009 Feb 27;8:35. doi: 10.1186/1475-2875-8-35.
Whilst a large number of malaria antigens are being tested as candidate malaria vaccines, a major barrier to the development of an effective vaccine is the lack of a suitable human adjuvant capable of inducing a strong and long lasting immune response. In this study, the ability of AFCo1, a potent T and B cell adjuvant based on cochleate structures derived from meningococcal B outer membrane proteoliposomes (MBOMP), to boost the immune response against two Plasmodium falciparum antigens, merozoite surface protein 4 (MSP4) and 5 (MSP5), was evaluated.
Complete Freund's adjuvant (CFA), which is able to confer protection against malaria in animal MSP4/5 vaccine challenge models, was used as positive control adjuvant. MSP4 and 5-specific IgG, delayed-type hypersensitivity (DTH), T-cell proliferation, and cytokine production were evaluated in parallel in mice immunized three times intramuscularly with MSP4 or MSP5 incorporated into AFCo1, synthetic cochleate structures, CFA or phosphate buffered saline.
AFCo1 significantly enhanced the IgG and T-cell response against MSP4 and MSP5, with a potency equivalent to CFA, with the response being characterized by both IgG1 and IgG2a isotypes, increased interferon gamma production and a strong DTH response, consistent with the ability of AFCo1 to induce Th1-like immune responses.
Given the proven safety of MBOMP, which is already in use in a licensed human vaccine, AFCo1 could assist the development of human malaria vaccines that require a potent and safe adjuvant.
虽然大量疟疾抗原正在作为候选疟疾疫苗进行测试,但开发有效疫苗的一个主要障碍是缺乏一种能够诱导强烈且持久免疫反应的合适人类佐剂。在本研究中,评估了AFCo1(一种基于源自B群脑膜炎球菌外膜蛋白脂质体(MBOMP)的螺旋形结构的强效T细胞和B细胞佐剂)增强针对两种恶性疟原虫抗原——裂殖子表面蛋白4(MSP4)和5(MSP5)的免疫反应的能力。
能够在动物MSP4/5疫苗攻毒模型中提供疟疾保护的完全弗氏佐剂(CFA)用作阳性对照佐剂。在分别用掺入AFCo1、合成螺旋形结构、CFA或磷酸盐缓冲盐水的MSP4或MSP5进行三次肌肉注射免疫的小鼠中,平行评估MSP4和5特异性IgG、迟发型超敏反应(DTH)、T细胞增殖和细胞因子产生情况。
AFCo1显著增强了针对MSP4和MSP5的IgG和T细胞反应,效力与CFA相当,反应特征为IgG1和IgG2a两种亚型、干扰素γ产生增加以及强烈的DTH反应,这与AFCo1诱导类似Th1免疫反应的能力一致。
鉴于已在一种已获许可的人类疫苗中使用的MBOMP已被证明具有安全性,AFCo1可以助力需要强效且安全佐剂的人类疟疾疫苗的开发。