Pérez O, Lastre M, Cabrera O, del Campo J, Bracho G, Cuello M, Balboa J, Acevedo R, Zayas C, Gil D, Mora N, González D, Pérez R, González E, Barberá R, Fajardo E M, Sierra G, Solís R L, Campa C
Immunology Department, Finlay Institute, Havana City, Cuba.
Scand J Immunol. 2007 Aug-Sep;66(2-3):271-7. doi: 10.1111/j.1365-3083.2007.01981.x.
Neisseria meningitidis B proteoliposome (AFPL1 when used as adjuvant) and its derivative-Cochleate (AFCo1) contain immunopotentiating and immunomodulating properties and delivery system capacities required for a good adjuvant. Additionally, they contain meningococcal protective antigens and permit packaging of other antigens and pathogen-associated molecular patterns (PAMP). Consequently, we hypothesized that they would function as good vaccine adjuvants for their own antigens and also for non-related antigens. AFPL1 is a detergent-extracted outer membrane vesicle of N. meningitidis B transformed into AFCo1 in calcium environment. Both are produced at Finlay Institute under good manufacture practices (GMP) conditions. We show their exceptional characteristics: combining in the same structure, the potentiator activity, polarizing agents and delivery system capacities; presenting multimeric protein copies; containing multiprotein composition and multi and synergistic PAMP components; acting with incorporated or co-administrated antigens; inducing type I IFN-gamma and IL-12 cytokines suggesting the stimulation of human plasmocytoid precursor and conventional dendritic cells, respectively, inducing a preferential Th1 immune response with TCD4(+), TCD8(+), cross-presentation and cytotoxic T-lymphocyte (CTL) in vivo responses; and functioning by parenteral and mucosal routes. AFPL1-AFCo1 protective protein constitutions permit per se their function as a vaccine. In addition to Phase IV Men BC vaccine, AFPL1 has ended the preclinical stage in an allergy vaccine and is concluding the preclinical stage of a nasal meningococcal vaccine. In conclusion, AFPL1 and AFCo1 induced signal 1, 2 and 3 polarizing to a Th1 (including CTL) response when they acted directly as vaccines or were used as adjuvants with incorporated or co-administered antigens by parenteral or mucosal routes. Both are very promising adjuvants.
B群脑膜炎奈瑟菌蛋白脂质体（用作佐剂时为AFPL1）及其衍生物 - 卷曲体（AFCo1）具有良好佐剂所需的免疫增强、免疫调节特性和递送系统能力。此外，它们含有脑膜炎球菌保护性抗原，并允许包装其他抗原和病原体相关分子模式（PAMP）。因此，我们推测它们对于自身抗原以及非相关抗原都将作为良好的疫苗佐剂发挥作用。AFPL1是从B群脑膜炎奈瑟菌中用去污剂提取的外膜囊泡，在钙环境中转化为AFCo1。两者均在芬莱研究所按照良好生产规范（GMP）条件生产。我们展示了它们的卓越特性：在同一结构中结合了增强活性、极化剂和递送系统能力；呈现多聚体蛋白拷贝；含有多蛋白组成以及多种协同的PAMP成分；与掺入或共同给药的抗原起作用；诱导I型干扰素 - γ和IL - 12细胞因子，分别提示刺激人浆细胞样前体和传统树突状细胞，在体内诱导优先的Th1免疫反应以及TCD4(+)、TCD8(+)、交叉呈递和细胞毒性T淋巴细胞（CTL）反应；并且通过胃肠外和黏膜途径发挥作用。AFPL1 - AFCo1保护性蛋白组成本身使其具有疫苗功能。除了IV期B群脑膜炎球菌结合疫苗外，AFPL1在一种过敏疫苗中已结束临床前阶段，并且正在完成一种鼻用脑膜炎球菌疫苗的临床前阶段。总之，当AFPL1和AFCo1直接作为疫苗或通过胃肠外或黏膜途径与掺入或共同给药的抗原一起用作佐剂时，它们诱导信号1、2和3极化至Th1（包括CTL）反应。两者都是非常有前景的佐剂。
