Tacket C O, Hone D M, Losonsky G A, Guers L, Edelman R, Levine M M
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201.
Vaccine. 1992;10(7):443-6. doi: 10.1016/0264-410x(92)90392-w.
An attenuated Salmonella typhi strain has been sought as an improved oral typhoid vaccine and as a carrier of protective antigens of other pathogens to make hybrid vaccines. Ideally, such a strain would be safe and induce protective immune responses after a single oral dose. CVD 908 is a mutant of S. typhi wild-type strain Ty2 with recombinant deletions in two genes, aroC and aroD. In phase 1 testing to date, this strain has not produced febrile responses or other significant adverse reactions in adult volunteers given doses of 5 x 10(4) to 5 x 10(7) organisms with sodium bicarbonate. In addition, after just a single oral dose of 5 x 10(7) colony-forming units, this strain induced IgG seroconversion to S. typhi lipopolysaccharide in 83% of vaccinees and stimulated specific IgA-secreting gut-derived lymphocytes in 100% of vaccinees. CVD 908 is a new oral typhoid vaccine that should be further investigated as a carrier for expressing foreign antigens in recombinant vaccine constructs.
人们一直在寻找一种减毒伤寒沙门氏菌菌株，作为一种改进的口服伤寒疫苗以及作为其他病原体保护性抗原的载体来制备联合疫苗。理想情况下，这样的菌株应是安全的，并且在单次口服给药后能诱导产生保护性免疫反应。CVD 908是伤寒沙门氏菌野生型菌株Ty2的一个突变体，在aroC和aroD这两个基因中有重组缺失。在迄今为止的1期试验中，给成年志愿者口服5×10⁴至5×10⁷个该菌株与碳酸氢钠的混合物后，该菌株未引起发热反应或其他明显不良反应。此外，仅单次口服5×10⁷个菌落形成单位后，该菌株在83%的接种者中诱导了针对伤寒沙门氏菌脂多糖的IgG血清转化，并在100%的接种者中刺激了肠道来源的分泌特异性IgA的淋巴细胞。CVD 908是一种新型口服伤寒疫苗，作为重组疫苗构建体中表达外源抗原的载体，应进一步开展研究。
