Black R, Levine M M, Young C, Rooney J, Levine S, Clements M L, O'Donnell S, Hugues T, Germanier R
Dev Biol Stand. 1983;53:9-14.
Ty21a, a stable attenuated mutant of Salmonella typhi, is a safe, protective oral vaccine when 3 doses of 10(9) cells in saline are taken after neutralization of gastric acidity by 1 g NaHCO3. To identify a more convenient method to administer vaccine and to determine the feasibility of immunizing with a single dose, we studied the immune response of children and adults to different formulations of Ty21a with a newly developed, sensitive, enzyme-linked immunosorbent assay (ELISA). In this ELISA, a rise in S. typhi O antibody was defined as a change in net optical density of greater than or equal to 0.15 (more than 3 SD from the mean difference in optical density in a negative control population). Three hundred and thirty-five Chilean children were given 3 doses of 10(9) Ty21a in 150 ml of milk with 0.8 g NaHCO3 or in enteric-coated capsules. In each group, 5% seroconverted by Widal O but 41% by IgG ELISA O antibody titers; mean antibody levels by group were identical. Studies were also carried out in healthy college students in a non-endemic area (U.S.A.) who had no history of prior typhoid immunization. In total, 141 U.S. adults received vaccine formulated in either one of two ways: 1) in gelatin capsules administered with two additional gelatin capsules containing a total of 0.8 gm NaHCO3 or 2) in enteric-coated capsules. Thirty-six persons received one dose, 30 got two doses and 16 ingested three doses of enteric-coated vaccines, while 44 persons receiving one dose and 15 got two doses of vaccine in the gelatin capsule formulation. Rates of seroconversion of ELISA O antibody were similar in all the groups. Ty21a vaccine was not recovered from multiple stool, jejunal fluid or blood cultures of the U.S. vaccine recipients. Based on these observations a large-scale field trial of efficacy has been initiated in 90.000 schoolchildren 6-20 years of age in Santiago, Chile, of whom one-third received one dose of enteric-coated vaccine, one-third got two doses and the remainder received placebo.
Ty21a是伤寒沙门氏菌的一种稳定减毒突变株，当在服用1g碳酸氢钠中和胃酸后服用3剂含10⁹个菌的生理盐水悬液时，它是一种安全有效的口服疫苗。为了确定一种更方便的疫苗接种方法并确定单剂量免疫的可行性，我们采用新开发的灵敏酶联免疫吸附测定（ELISA）研究了儿童和成人对不同剂型Ty21a的免疫反应。在这种ELISA中，伤寒沙门氏菌O抗体升高定义为净光密度变化大于或等于0.15（比阴性对照人群光密度平均差异的3个标准差以上）。335名智利儿童服用了3剂含10⁹个Ty21a的150ml加0.8g碳酸氢钠的牛奶悬液或肠溶胶囊。每组中，通过维达尔O试验5%的人血清阳转，而通过IgG ELISA O抗体滴度检测41%的人血清阳转；各组的平均抗体水平相同。还对美国一个非流行地区、无伤寒免疫史的健康大学生进行了研究。总共141名美国成年人接受了两种剂型之一的疫苗：1）装在明胶胶囊中，并额外服用两粒共含0.8g碳酸氢钠的明胶胶囊；2）肠溶胶囊。36人接受一剂，30人接受两剂，16人服用三剂肠溶疫苗，而44人接受一剂、15人接受两剂明胶胶囊剂型的疫苗。所有组中ELISA O抗体的血清阳转率相似。在美国疫苗接种者的多次粪便、空肠液或血液培养物中均未检出Ty21a疫苗。基于这些观察结果，已在智利圣地亚哥对90000名6至20岁的学童开展了一项大规模疗效现场试验，其中三分之一的儿童接受一剂肠溶疫苗，三分之一接受两剂，其余儿童接受安慰剂。
