Kundu Juthika, Mazumder Rupa, Srivastava Ranjana, Srivastava Brahm S
Division of Microbiology, Central Drug Research Institute, Lucknow, India.
FEMS Immunol Med Microbiol. 2009 Jul;56(2):179-84. doi: 10.1111/j.1574-695X.2009.00563.x. Epub 2009 May 5.
Intranasal immunization, a noninvasive method of vaccination, has been found to be effective in inducing systemic and mucosal immune responses. The present study was aimed at investigating the efficacy of intranasal immunization in inducing mucosal immunity in experimental cholera by subunit recombinant protein vaccines from Vibrio cholerae O1. The structural genes encoding toxin-coregulated pilus A (TcpA) and B subunit of cholera toxin (CtxB) from V. cholerae O1 were cloned and expressed in Escherichia coli. Rabbits were immunized intranasally with purified TcpA and CtxB alone or a mixture of TcpA and CtxB. Immunization with TcpA and CtxB alone conferred, respectively, 41.1% and 70.5% protection against V. cholerae challenge, whereas immunization with a mixture of both antigens conferred complete (100%) protection, as assayed in the rabbit ileal loop model. Serum titers of immunoglobulin G (IgG) antibodies to TcpA and CtxB, and anti-TcpA- and anti-CtxB-specific sIgA in intestinal lavage of vaccinated animals were found to be significantly elevated compared with unimmunized controls. Vibriocidal antibodies were detected at remarkable levels in rabbits receiving TcpA antigen and their titers correlated with protection. Thus, mucosal codelivery of pertinent cholera toxoids provides enhanced protection against experimental cholera.
鼻内免疫是一种非侵入性的疫苗接种方法，已被发现可有效诱导全身和黏膜免疫反应。本研究旨在通过霍乱弧菌O1的亚单位重组蛋白疫苗，研究鼻内免疫在实验性霍乱中诱导黏膜免疫的效果。编码霍乱弧菌O1毒素协同菌毛A（TcpA）和霍乱毒素B亚单位（CtxB）的结构基因被克隆并在大肠杆菌中表达。用纯化的TcpA和CtxB单独或TcpA与CtxB的混合物对兔子进行鼻内免疫。在兔回肠袢模型中检测发现，单独用TcpA和CtxB免疫分别对霍乱弧菌攻击提供了41.1%和70.5%的保护，而用两种抗原的混合物免疫则提供了完全（100%）的保护。与未免疫的对照组相比，接种动物的血清中针对TcpA和CtxB的免疫球蛋白G（IgG）抗体滴度以及肠道灌洗液中抗TcpA和抗CtxB特异性分泌型免疫球蛋白A（sIgA）显著升高。在接受TcpA抗原的兔子中检测到显著水平的杀弧菌抗体，其滴度与保护作用相关。因此，相关霍乱类毒素的黏膜共同递送可增强对实验性霍乱的保护作用。
