Souza Patrícia R M, Zárate-Bladés Carlos R, Hori Juliana I, Ramos Simone G, Lima Deison S, Schneider Tatiana, Rosada Rogério S, Torre Lucimara G L, Santana Maria Helena A, Brandão Izaíra T, Masson Ana P, Coelho-Castelo Arlete A M, Bonato Vânia L, Galetti Fabio C S, Gonçalves Eduardo D, Botte Domingos A, Machado Jeanne B M, Silva Celio L
Universidade de São Paulo, Núcleo de Pesquisas em Tuberculose, Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, FMRP-USP, 14049-900 Ribeirão Preto, SP, Brasil.
Expert Opin Biol Ther. 2008 Sep;8(9):1255-64. doi: 10.1517/14712598.8.9.1255.
Tuberculosis is a major threat to human health. The high disease burden remains unaffected and the appearance of extremely drug-resistant strains in different parts of the world argues in favor of the urgent need for a new effective vaccine. One of the promising candidates is heat-shock protein 65 when used as a genetic vaccine (DNAhsp65). Nonetheless, there are substantial data indicating that BCG, the only available anti-TB vaccine for clinical use, provides other important beneficial effects in immunized infants.
We compared the protective efficacy of BCG and Hsp65 antigens in mice using different strategies: i) BCG, single dose subcutaneously; ii) naked DNAhsp65, four doses, intramuscularly; iii) liposomes containing DNAhsp65, single dose, intranasally; iv) microspheres containing DNAhsp65 or rHsp65, single dose, intramuscularly; and v) prime-boost with subcutaneous BCG and intramuscular DNAhsp65.
All the immunization protocols were able to protect mice against infection, with special benefits provided by DNAhsp65 in liposomes and prime-boost strategies.
Among the immunization protocols tested, liposomes containing DNAhsp65 represent the most promising strategy for the development of a new anti-TB vaccine.
结核病是对人类健康的重大威胁。高疾病负担仍未得到缓解，且在世界不同地区出现的极端耐药菌株表明迫切需要一种新的有效疫苗。有前景的候选疫苗之一是热休克蛋白65用作基因疫苗（DNAhsp65）。尽管如此，有大量数据表明，卡介苗作为唯一可用于临床的抗结核疫苗，在免疫接种的婴儿中具有其他重要的有益作用。
我们使用不同策略比较了卡介苗和热休克蛋白65抗原在小鼠中的保护效果：i）皮下注射单剂量卡介苗；ii）肌肉注射四剂裸DNAhsp65；iii）鼻内注射单剂量含DNAhsp65的脂质体；iv）肌肉注射单剂量含DNAhsp65或重组热休克蛋白65的微球；v）皮下注射卡介苗和肌肉注射DNAhsp65进行初免-加强免疫。
所有免疫方案均能保护小鼠免受感染，脂质体中的DNAhsp65和初免-加强免疫策略具有特别的益处。
在测试的免疫方案中，含DNAhsp65的脂质体是开发新型抗结核疫苗最有前景的策略。
