Li A, Kärnell A, Huan P T, Cam P D, Minh N B, Trâm L N, Quy N P, Trach D D, Karlsson K, Lindberg G
Karolinska Institute, Department of Clinical Bacteriology, Huddinge Hospital, Sweden.
Vaccine. 1993;11(2):180-9. doi: 10.1016/0264-410x(93)90015-p.
The live, auxotrophic dependent Shigella flexneri Y vaccine strain SFL124 with a deleted aroD gene was tested in 30 healthy adult male Vietnamese volunteers. A single dose of 2 x 10(9) live bacteria was given orally to 15 volunteers, whereas 15 received three doses every other day. None of the volunteers reacted with fever or diarrhoea and SFL124 was excreted by all for a mean of 2.8 (single dose) and 2.6 (three doses) days. A total of 27 of 30 (90%) and 26 of 30 (87%) responded with significantly (0.001 < p < 0.01) increased antibody-secreting cell (ASC) numbers against Shigella flexneri Y lipopolysaccharide (LPS) and invasion plasmid-coded antigens (Ipa). A faecal IgA antibody response to LPS and Ipa was seen in 20 of the 30 (67%) volunteers against both antigens. Serum antibody responses were seen in 23 of 30 (77%) against the LPS and in 17 of the 30 against Ipa. The three-dose schedule elicited only somewhat stronger immune responses than the single-dose schedule. A booster dose of 2 x 10(9) live bacteria was given to half of the volunteers in each group after 6 months, the other half received the same dose after 12 months. Following the booster at 6 or 12 months (i) the excretion of SFL124 was significantly shorter (p < 0.05) than after primary vaccination; (ii) the anti-S. flexneri LPS and anti-Ipa faecal sIgA titres were significantly higher (p < 0.05 to p < 0.01) than after primary vaccination; (iii) the anti-LPS and anti-Ipa ASC responses were significantly lower (p < 0.05) and of shorter duration than after primary vaccination, and (iv) the serum anti-LPS and anti-Ipa responses were significantly elevated (p < 0.05) and similar to those seen after primary vaccination. The results indicate that SFL124 is a safe, live vaccine strain with a negligible reactogenicity in adults living in a Shigella endemic area. SFL124 induces specific immune responses against LPS and Ipa with a mucosal memory lasting for at least 1 year.
对缺失aroD基因的活的、营养缺陷型依赖的福氏志贺菌Y疫苗株SFL124在30名健康成年越南男性志愿者中进行了测试。给15名志愿者口服单剂量2×10⁹活细菌，而另外15名志愿者每隔一天接受三剂。所有志愿者均未出现发热或腹泻反应，所有志愿者均排出SFL124，单剂量组平均排出2.8天，三剂量组平均排出2.6天。30名志愿者中有27名（90%）和26名（87%）针对福氏志贺菌Y脂多糖（LPS）和侵袭质粒编码抗原（Ipa）的抗体分泌细胞（ASC）数量显著增加（0.001＜p＜0.01）。30名志愿者中有20名（67%）针对两种抗原出现了对LPS和Ipa的粪便IgA抗体反应。30名志愿者中有23名（77%）出现了针对LPS的血清抗体反应，30名中有17名出现了针对Ipa的血清抗体反应。三剂量方案引发的免疫反应仅比单剂量方案略强。6个月后，每组一半的志愿者接受2×10⁹活细菌的加强剂量，另一半在12个月后接受相同剂量。在6个月或12个月进行加强免疫后：（i）SFL124的排出时间明显短于初次接种后（p＜0.05）；（ii）抗福氏志贺菌LPS和抗Ipa粪便分泌型IgA滴度明显高于初次接种后（p＜0.05至p＜0.01）；（iii）抗LPS和抗Ipa的ASC反应明显低于初次接种后（p＜0.05）且持续时间更短；（iv）血清抗LPS和抗Ipa反应明显升高（p＜0.05）且与初次接种后相似。结果表明，SFL124是一种安全的活疫苗株，在志贺菌流行地区的成年人中反应原性可忽略不计。SFL124诱导针对LPS和Ipa的特异性免疫反应，具有至少持续1年的黏膜记忆。
