Byrd Wyatt, Cassels Frederick J
Department of Enteric Infections, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
FEMS Immunol Med Microbiol. 2006 Mar;46(2):262-8. doi: 10.1111/j.1574-695X.2005.00039.x.
The immunogenicity induced in BALB/c mice following intranasal challenge with a viable nonlethal dose (1.2 x 10(8) CFU) of enterotoxigenic Escherichia coli (ETEC) strain E23477A (O139:H28:CS1:CS3:LT+:ST+) was studied over a 140-day period. Serum IgG and IgM antibodies against coli surface antigen 3 (CS3), O139 lipopolysaccharide and heat-labile enterotoxin were measured by day 14 and remained at elevated levels out to day 140. The serum IgG response to the somatic antigens (CS3 and O139 lipopolysaccharide) was significantly greater (P < 0.05) than the IgG response to heat-labile enterotoxin, and the serum IgG response to CS3 was significantly greater (P < 0.05) than the IgG response to O139 lipopolysaccharide. The predominant serum IgG subclasses to CS3 were IgG1 and IgG2a, and they were significantly greater (P < 0.05) than IgG2b and IgG3. The predominant serum IgG subclass response to O139 lipopolysaccharide was initially IgG3 until day 56, after which IgG1 was predominant. The serum subclass response to CS3 indicated a mixed T helper 1/2 (Th1/Th2) profile, whereas the response to O139 lipopolysaccharide was primarily that of a Th2-type, at least over time. Fecal IgG and IgA responses to CS3 and O139 lipopolysaccharide were detected by day 14 and were measured out to day 140, with the CS3 fecal antibody responses being significantly greater (P < 0.05) than the O139 lipopolysaccharide and heat-labile enterotoxin fecal antibody responses. The aim of this study is the development of the intranasal mouse model that can aid in better understanding the immunopathology of ETEC infection and in screening of vaccine candidates prior to volunteer trials.
在140天的时间里，研究了用活的非致死剂量（1.2×10⁸CFU）的产肠毒素大肠杆菌（ETEC）菌株E23477A（O139:H28:CS1:CS3:LT⁺:ST⁺）经鼻内攻击BALB/c小鼠后诱导的免疫原性。在第14天时测量了针对大肠杆菌表面抗原3（CS3）、O139脂多糖和热不稳定肠毒素的血清IgG和IgM抗体，并且这些抗体水平在第140天时仍维持在升高状态。血清IgG对菌体抗原（CS3和O139脂多糖）的反应显著大于（P<0.05）对热不稳定肠毒素的IgG反应，并且血清IgG对CS3的反应显著大于（P<0.05）对O139脂多糖的IgG反应。针对CS3的主要血清IgG亚类是IgG1和IgG2a，并且它们显著大于（P<0.05）IgG2b和IgG3。针对O139脂多糖的主要血清IgG亚类反应在第56天之前最初是IgG3，之后IgG1占主导。血清亚类对CS3的反应表明是混合的辅助性T细胞1/2（Th1/Th2）特征，而对O139脂多糖的反应至少随着时间推移主要是Th2型的。在第14天时检测到粪便对CS3和O139脂多糖的IgG和IgA反应，并测量至第140天，粪便中针对CS3的抗体反应显著大于（P<0.05）针对O139脂多糖和热不稳定肠毒素的粪便抗体反应。本研究的目的是开发鼻内小鼠模型，该模型有助于更好地理解ETEC感染的免疫病理学，并在志愿者试验之前筛选候选疫苗。
