表达墨西哥利什曼原虫主要表面蛋白gp63的伤寒沙门氏菌CVD 908候选疫苗株的免疫原性。

Immunogenicity of a Salmonella typhi CVD 908 candidate vaccine strain expressing the major surface protein gp63 of Leishmania mexicana mexicana.

作者信息

González C R, Noriega F R, Huerta S, Santiago A, Vega M, Paniagua J, Ortiz-Navarrete V, Isibasi A, Levine M M

机构信息

Unidad de Investigación Médica en Inmunoquímica, México, D.F., México.

出版信息

Vaccine. 1998 May-Jun;16(9-10):1043-52. doi: 10.1016/s0264-410x(97)00267-3.

DOI:10.1016/s0264-410x(97)00267-3

PMID:9682357

Abstract

Attenuated Salmonella typhi are attractive for use as live vector vaccines to express protozoal antigens and deliver them to the human immune system. The gene encoding the mature form of Leishmania mexicana mexicana gp63 under control of tac promoter was integrated into the delta aroC locus of the chromosome of attenuated delta aroC, delta aroD S. typhi strain CVD 908. After oral immunization of BALB/c mice with two 1 x 10(9) colony forming unit doses given 21 days apart, CVD 908 omega (delta aroC::Ptac-gp63) elicited a broad T cell-mediated immune response against L. m. mexicana gp63 as demonstrated by: (1) lymphoproliferative response to fixed whole L. m. mexicana promastigotes; (2) activation of IL-2 (but not IL-4)-producing lymphocytes; (3) appearance of cytotoxic T cells against mouse mastocytoma cells expressing gp63. This T-cell mediated immune response was associated with significant protection in F1 (BALB/cXC57Bl/6) mice challenged in their footpads with a wild type strain of L. m. mexicana.

摘要

减毒伤寒沙门氏菌作为活载体疫苗来表达原生动物抗原并将其递送至人体免疫系统很有吸引力。在tac启动子控制下，编码墨西哥利什曼原虫成熟形式gp63的基因被整合到减毒的aroC缺失、aroD缺失伤寒沙门氏菌菌株CVD 908染色体的aroC缺失位点。在用两个间隔21天的1×10⁹菌落形成单位剂量对BALB/c小鼠进行口服免疫后，CVD 908ω（aroC缺失::Ptac-gp63）引发了针对墨西哥利什曼原虫gp63的广泛T细胞介导的免疫反应，表现为：（1）对固定的完整墨西哥利什曼原虫前鞭毛体的淋巴细胞增殖反应；（2）产生IL-2（而非IL-4）的淋巴细胞的激活；（3）出现针对表达gp63的小鼠肥大细胞瘤细胞的细胞毒性T细胞。这种T细胞介导的免疫反应与在用墨西哥利什曼原虫野生型菌株攻击其足垫的F1（BALB/c×C57Bl/6）小鼠中显著的保护作用相关。