Baudner Barbara C, Giudice Giuseppe Del
Novartis Vaccines and Diagnostics, Siena, Italy.
Methods Mol Biol. 2010;626:261-85. doi: 10.1007/978-1-60761-585-9_18.
Mucosal vaccination offers the advantage of blocking pathogens at the portal of entry, improving patient's compliance, facilitating vaccine delivery, and decreasing the risk of unwanted spread of infectious agents via contaminated syringes.Recent advances in vaccinology have created an array of vaccine constructs that can be delivered to mucosal surfaces of the respiratory, gastrointestinal, and genitourinary tracts using intranasal, oral, and vaginal routes. Due to the different characteristics of mucosal immune response, as compared with systemic response, mucosal immunization requires particular methods of antigen presentation. Well-tolerated adjuvants that enhance the efficacy of such vaccines will play an important role in mucosal immunization. Among promising mucosal adjuvants, mutants of cholera toxin and the closely related heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli present powerful tools, augmenting the local and systemic serum antibody response to co-administered antigens.In this chapter, we describe the formulation and application of vaccines using the genetically modified LTK63 mutant as a prototype of the family of these mucosal adjuvants and the tools to determine its activity in the mouse model.
黏膜疫苗接种具有在病原体进入门户处阻断病原体、提高患者依从性、便于疫苗递送以及降低通过受污染注射器导致感染因子意外传播风险等优势。疫苗学的最新进展产生了一系列疫苗构建体，这些构建体可通过鼻内、口服和阴道途径递送至呼吸道、胃肠道和泌尿生殖道的黏膜表面。由于与全身免疫反应相比，黏膜免疫反应具有不同的特征，黏膜免疫需要特定的抗原呈递方法。耐受性良好且能增强此类疫苗效力的佐剂将在黏膜免疫中发挥重要作用。在有前景的黏膜佐剂中，霍乱毒素突变体以及产肠毒素大肠杆菌的密切相关的不耐热肠毒素（LT）是强大的工具，可增强对共同施用抗原的局部和全身血清抗体反应。在本章中，我们描述了以基因改造的LTK63突变体作为这些黏膜佐剂家族的原型的疫苗的配方和应用，以及在小鼠模型中确定其活性的工具。
