Bastien N, Trudel M, Simard C
Institut Armand-Frappier, Centre de recherche en virologie, Laval des Rapides, Que., Canada.
Vaccine. 1999 Feb 26;17(7-8):832-6. doi: 10.1016/s0264-410x(98)00267-9.
We have previously shown that intraperitoneal immunization of BALB/c mice with the 14 amino-acid long synthetic peptides G/174-187 and BG/174-187, representing the region 174-187 of the G-glycoprotein from human (H) and bovine (B) respiratory syncytial virus (RSV), respectively, completely protects animals from infection with the corresponding virus. A current goal in vaccine development being the delivery of noninvasive protective antigens via mucosal surfaces, we have evaluated the immunogenicity and protective efficacy of the two peptides when administered to mice by the intranasal (i.n.) route in the presence or absence of the cholera toxin (CT) as a mucosal adjuvant. The two peptides given alone induced the production of RSV-specific circulating IgG, as revealed by ELISA titers of immune sera. When the peptides were administered intranasally with CT, the higher IgG antibody titer which was induced was within the same order of magnitude as that obtained following i.n. immunization with live RSV or intraperitoneal injection with the peptides, thus demonstrating the stimulatory effect of the CT adjuvant. Moreover, although the peptides fail to induce a detectable level of secretory IgA, all animals immunized i.n. with peptide BG/174-187 (plus or minus CT) and all those immunized with peptide G/174-187 mixed with CT were completely resistant to infection by the corresponding virus. To our knowledge, this is the first study reporting that complete protection against a natural pathogen can be elicited by mucosally delivered synthetic peptides. This supports the usefulness of synthetic peptides in prophylactic vaccination.
我们之前已经表明,用分别代表人类(H)和牛(B)呼吸道合胞病毒(RSV)G糖蛋白174 - 187区域的14个氨基酸长的合成肽G/174 - 187和BG/174 - 187对BALB/c小鼠进行腹腔免疫,可使动物完全免受相应病毒的感染。疫苗开发的当前目标之一是通过粘膜表面递送非侵入性保护性抗原,因此我们评估了在有或无霍乱毒素(CT)作为粘膜佐剂的情况下,通过鼻内(i.n.)途径给小鼠施用这两种肽时的免疫原性和保护效果。单独给予这两种肽可诱导产生RSV特异性循环IgG,这通过免疫血清的ELISA滴度得以揭示。当肽与CT一起经鼻内给药时,诱导产生的较高IgG抗体滴度与经鼻内用活RSV免疫或经腹腔注射肽后获得的滴度处于同一数量级,从而证明了CT佐剂的刺激作用。此外,尽管这些肽未能诱导出可检测水平的分泌型IgA,但所有经鼻内用肽BG/174 - 187(加或不加CT)免疫的动物以及所有用与CT混合的肽G/174 - 187免疫的动物对相应病毒的感染均完全具有抵抗力。据我们所知,这是第一项报道通过粘膜递送合成肽可引发对天然病原体的完全保护的研究。这支持了合成肽在预防性疫苗接种中的实用性。