Mastroeni P, Chabalgoity J A, Dunstan S J, Maskell D J, Dougan G
Centre for Veterinary Science, University of Cambridge, Madingley Road, Cambridge, CB3 OES, UK.
Vet J. 2001 Mar;161(2):132-64. doi: 10.1053/tvjl.2000.0502.
Salmonella infections are a serious medical and veterinary problem world-wide and cause concern in the food industry. Vaccination is an effective tool for the prevention of Salmonella infections. Host resistance to Salmonella relies initially on the production of inflammatory cytokines leading to the infiltration of activated inflammatory cells in the tissues. Thereafter T- and B-cell dependent specific immunity develops allowing the clearance of Salmonella microorganisms from the tissues and the establishment of long-lasting acquired immunity to re-infection. The increased resistance that develops after primary infection/ vaccination requires T-cells cytokines such as IFNgamma TNFalpha and IL12 in addition to opsonising antibody. However for reasons that are not fully understood seroconversion and/or the presence of detectable T-cell memory do not always correlate with the development of acquired resistance to infection.Whole-cell killed vaccines and subunit vaccines are used in the prevention of Salmonella infection in animals and in humans with variable results. A number of early live Salmonella vaccines derived empirically by chemical or u.v. mutagenesis proved to be immunogenic and protective and are still in use despite the need for repeated parenteral administration. Recent progress in the knowledge of the genetics of Salmonella virulence and modern recombinant DNA technology offers the possibility to introduce multiple defined attenuating and irreversible mutations into the bacterial genome. This has recently allowed the development of Salmonella strains devoid of significant side effects but still capable of inducing solid immunity after single oral administration. Live attenuated Salmonella vaccines have been used for the expression of heterologous antigens/proteins that can be successfully delivered to the immune system. Furthermore Salmonella can transfer plasmids encoding foreign antigens under the control of eukaryotic promoters (DNA vaccines) to antigen-presenting cells resulting in targeted delivery of DNA vaccines to these cells. Despite the great recent advances in the development of Salmonella vaccines a large proportion of the work has been conducted in laboratory rodents and more research in other animal species is required.
沙门氏菌感染是一个全球性的严重医学和兽医问题，在食品行业也引发了关注。疫苗接种是预防沙门氏菌感染的有效手段。宿主对沙门氏菌的抵抗力最初依赖于炎症细胞因子的产生，这会导致活化的炎症细胞浸润到组织中。此后，依赖T细胞和B细胞的特异性免疫开始发展，使得组织中的沙门氏菌微生物得以清除，并建立起对再次感染的持久获得性免疫。初次感染/接种疫苗后产生的增强抵抗力，除了调理抗体外，还需要T细胞细胞因子，如干扰素γ、肿瘤坏死因子α和白细胞介素12。然而，由于尚未完全明确的原因，血清转化和/或可检测到的T细胞记忆的存在并不总是与获得性抗感染能力的发展相关。全细胞灭活疫苗和亚单位疫苗用于预防动物和人类的沙门氏菌感染，效果各异。一些通过化学或紫外线诱变经验性获得的早期活沙门氏菌疫苗被证明具有免疫原性和保护性，尽管需要重复进行肠胃外给药，但仍在使用。沙门氏菌毒力遗传学知识和现代重组DNA技术的最新进展，使得在细菌基因组中引入多个明确的减毒和不可逆突变成为可能。这最近使得开发出了副作用极小但单次口服后仍能诱导强大免疫力的沙门氏菌菌株。减毒活沙门氏菌疫苗已被用于表达可成功递送至免疫系统的异源抗原/蛋白质。此外，沙门氏菌可在真核启动子（DNA疫苗）的控制下将编码外源抗原的质粒转移至抗原呈递细胞，从而实现DNA疫苗向这些细胞的靶向递送。尽管沙门氏菌疫苗的开发最近取得了巨大进展，但大部分工作是在实验啮齿动物中进行的，还需要在其他动物物种中开展更多研究。
