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口服伤寒活菌苗的改善可通过使伤寒杆菌中特异毒力基因缺失的基因工程来进行.Ty445是一个aroA缺失的鼠伤寒杆菌Ty2株,同时亦缺失pho P/phoQ鼠伤寒杆菌毒力调节基因座.作者在志愿者中采用不同的剂量(5×10~5cfu~2×10~(10)cfu)和不同接种程序(1剂和2剂接种)对Ty445进行试验,观察接种后的临床应答和副作用,同时进行细菌学和血清学研究.结果表明,接受小于10~9cfu者均未出现任何副作用.在服2剂10~(10)cfu的14人中,仅1人出现短时的轻度腹泻,6人出现短时非特异性腹部症状(如腹鸣、胃部不适等).粪细菌学培养结果表明,在仅服1剂的12人中,8人粪培养至少1次阳性;服2剂菌苗的14人均至少1次粪培养阳性.在服2剂菌苗的14人中,8人服苗前预服了碳酸氢钠,6人预服了盐水,预服碳酸氢钠者的初次粪培养阳性率高于预服盐水者(分别为7/8和2/6).28天时无一受试者粪培养为阳性.血清学ELISA测定选用Ty445全菌体和O抗原两种包被抗原,并以8名服4剂Ty21a者作对照.结果显示,对照组中,5人血清抗
The improvement of oral typhoid live vaccine can be carried out through the genetic engineering of deletion of the specific virulence gene in typhoid bacillus.Ty445 is a tyrosinase-negative typhimurium Ty2 strain with deletion of pho P / phoQ Salmonella typhimurium virulence regulator The volunteers in different doses (5 × 10 ~ 5cfu ~ 2 × 10 ~ (10) cfu) and different vaccination programs (1 and 2 vaccination) Ty445 were tested to observe the clinical response after vaccination And side effects, both bacteriological and serological studies results showed that those receiving less than 10 ~ 9cfu did not have any side effects.Of two doses of 10 ~ (10) cfu of 14 people, only 1 short-term light Degree of diarrhea, 6 patients showed short-term non-specific abdominal symptoms (such as abdominal discomfort, stomach discomfort, etc.) Fecal bacteriological culture results showed that in 12 people serving only one dose, 8 human feces cultured at least once positive; 14 out of 2 vaccine strains were positive for faecal culture at least once.Of 14 of the 14 patients who took 2 vaccine strains, 8 people served pre-seedlings with sodium bicarbonate and 6 were served with salt water and sodium bicarbonate The positive rate of initial feces culture was higher than that of the pre-treated saline (7/8 and 2/6, respectively) and no feces was positive at 28 days Serum ELISA Ty445 whole cell selection and two kinds of coating antigen O antigen, and 4 to 8 Ty21a by serving as a control. The results showed that in the control group, anti-human serum 5