SAFETY AND IMMUNOGENICITY OF THE LIVE ORAL AUXOTROPHIC SHIGELLA-FLEXNERI SFL124 IN VOLUNTEERS

被引:37
作者
LI, A
PAL, T
FORSUM, U
LINDBERG, AA
机构
[1] KAROLINSKA INST,HUDDINGE HOSP,DEPT CLIN BACTERIOL,S-14186 HUDDINGE,SWEDEN
[2] UNIV PECS,SCH MED,INST MICROBIOL,H-7643 PECS,HUNGARY
关键词
SHIGELLA-FLEXNERI; ORAL VACCINATION; HUMANS; SAFETY; IMMUNOGENICITY;
D O I
10.1016/0264-410X(92)90070-Z
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The live, aromatic dependent Shigella flexneri Y vaccine strain SFL124, with a deleted aroD gene, was tested for safety and immunogenicity in 21 healthy adult volunteers. A single dose of 2 x 10(9) live bacteria was given orally to ten volunteers, whereas 11 received three doses every other day. The vaccine was excreted for 4.2 days and was well tolerated by 90.5% of the vaccines. Only 2 of 21 (9.5%) after the first dose had a self-limiting diarrhoea lasting 1 day; of volunteers given one dose only 3 of 10 showed anti-lipopolysaccharide (LPS) and anti-invasion plasmid coded antigen (Ipa) responses in serum. A faecal antibody response to LPS and Ipa was seen in six and three persons, respectively. Volunteers given three doses reacted with serum anti-LPS (9/11) and anti-Ipa (5/11) antibody responses. In stool, anti-LPS and anti-Ipa responses were detected in nine and eight volunteers, respectively. A booster dose of 2 x 10(9) bacteria given to six volunteers in the three-dose group 9-10 months later elicited high stool sIgA responses, indicating a strong mucosal memory, and was accompanied by a short excretion period of SFL124 (1.8 versus 4.2 days, p < 0.05). The vaccination also elicited antibody-secreting cell (ASC) responses against LPS in peripheral blood: the three doses of the vaccine resulted in a stronger response than did the single dose, while the booster dose elicited only a limited ASC response. Volunteers previously exposed to shigellae exhibited stronger anti-Ipa responses in serum and stool suggestive of an immunological memory to the Ipa. The results indicate that SFL124 is a safe live vaccine strain inducing specific immune responses against LPS and Ipa with a mucosal immune memory lasting for at least 9 months.
引用
收藏
页码:395 / 404
页数:10
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