重组沙门菌载体HIV-12F5表位疫苗毒力及分布  

Toxicity and biological distribution of attenuated Salmonella typhimurium bearing HIV-1 2F5 epitope in BALB/c mice

作　　者：李庆海[1] 陈文江[1] 刘树林[2] 凌虹[1] 

机构地区：[1]哈尔滨医科大学微生物学教研室,哈尔滨150081 [2]哈尔滨医科大学微生物基因组学和病原学研究中心

出　　处：《中国公共卫生》2008年第8期1004-1005,共2页Chinese Journal of Public Health

基　　金：国家自然科学基金项目(30771910);哈尔滨医科大学研究生创新基金

摘　　要：目的研究表达Ⅰ型人类免疫缺陷病毒（HIV-1）2F5表位的重组沙门菌（SA-2F5）对BALB／c小鼠的半数致死量（LD50），并观察其在小鼠体内的生物学分布。方法BALB／c小鼠随机分8组，以0，10^4～10^10菌落形成单位（CFU）重组菌灌胃，30d后用改良寇氏法测定LD50;BALB／c小鼠随机分2组，灌胃给予10^7 CFU重组沙门菌或磷酸盐缓冲液（PBS），分别于感染后第3，9，16，30d，无菌操作取各组肝、脾、肠系膜淋巴结，检测重组沙门菌在小鼠体内的分布。结果SA-2F5对BALB／c小鼠的LD，0为1．45×10^9CFU；感染后第3d，肝、脾、肠系膜淋巴结活菌数依次为5．38×10^4，4．87×10^4，9．08×10^3CFU。第9d各脏器活菌数分别降至7．35×10^2，7．50×10^2及3．00×10^2CFU。第16d各脏器活菌数基本与第9d相当。之后各脏器中活菌数持续下降，至第30d肝、脾内检测不到活菌，肠系膜淋巴结内活菌为2．1×10^2CFU。结论重组沙门菌SA-2F5毒力显著降低，在小鼠体内具有良好的生物学分布。Objective To investigate the median lethal dose（LDs0） and biological distribution of an attenuated Salmondla typhimurium strain, SA- 2F5, with the 2F5 epitope of human immunodeficiency virus type 1 （HIV- 1） in BALB/c mice. Methods BALB/c mice were randomly divided into eight groups, infected intragastrically with PBS or 10^4 -- 10^10 colony forming units （CFU） of S. typhimurium SA - 2F5 and monitored over a 30 - day period, and LD50 value was calculated. For detecting the presence of the bacteria in tissues, BALB/c mice were randomly divided into two groups and inoculated intragastrically with 10^7CFU SA - 2F5 or PBS. Livers, spleens and mesenteric lymph nodes were isolated from inoculated mice on 3, 9, 16 or 30 days post - inoculation and numbers of live bacteria in each organ were counted. Results LDs0 of SA- 2F5 to BALB/c mice was 1.45 × 10^9 CFU. The recombinant Salmonella strain could proliferate in livers, spleens and mesenteric lymph nodes of infected mice. The numbers of live bacteria within livers, spleens and mesenteric lymph nodes were 5.38 × 10^4CFU, 4.87 × 10^4CFU and 9.08 × 10^3CFU respectively on 3 days post - inoculation, and decreased to 7.35 × 10^2CFU, 7.50 × 10^2CFU and 3.00 × 10^2CFU respectively on 9 days post - inoculation. The situation of 16 day was similar to that of 9 days. There was no bacterium present in above organs on 30 days post - inoculation, except 2.1 × 10^2CFU in mesenteric lymph nodes. Conclusion Compared with wild type strains, the recombinant Salmonella was significantly attenuated and had a broad distribution in tissues of the BALB/c mice.

关 键 词：Ⅰ型人类免疫缺陷病毒 包膜 表位 重组鼠伤寒沙门菌 半数致死量(LD50) 

分 类 号：R392[医药卫生—免疫学]