Kärnell A, Cam P D, Verma N, Lindberg A A
Karolinska Institute, Department of Clinical Bacteriology, Huddinge Hospital, Sweden.
Vaccine. 1993;11(8):830-6. doi: 10.1016/0264-410x(93)90358-5.
The aromatic-dependent live Shigella flexneri 2a vaccine strain SFL1070, with a deleted aroD gene, had a much reduced intracellular growth in HeLa cells compared with its parent strain S. flexneri 2457T. S. flexneri SFL1070 gave no adverse effects in eight Macaca fascicularis monkeys orally vaccinated with four doses of 1 x 10(11) live bacteria within a 5-week period, whereas S. flexneri 2457T caused dysentery in all eight non-vaccinated monkeys. Thus the aromatic dependency rendered S. flexneri SFL1070 significantly attenuated (p = 0.00008). Significant intestinal S. flexneri lipopolysaccharide (LPS)-specific sIgA responses were seen in seven of eight vaccinated monkeys (p < 0.01) after four doses with SFL1070. However, serum IgG or IgA responses to various S. flexneri LPS antigens and the invasion plasmid antigens (Ipa-s) were seen in only four of eight vaccinated monkeys. The serum IgG titre increases against S. flexneri Y and 2a LPS reached significant levels (p < or = 0.05). All but one of the vaccinated monkeys were protected against oral challenge with 1 x 10(10) or 1 x 10(11) live S. flexneri 2457T given 2 weeks after the last vaccination. The protection was highly significant (p = 0.0007) as all non-vaccinated monkeys challenged with equal doses of strain 2457T developed dysentery. Three of them succumbed. Challenge infection of vaccinated monkeys elicited serum IgA and IgG responses to the homologous S. flexneri 2a LPS in three monkeys each (0.005 < or = p < or = 0.025). Serum IgA and IgG responses to the Ipa-s were seen in five and four monkeys each (0.01 < p < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
依赖芳香族氨基酸的福氏志贺菌2a活疫苗株SFL1070缺失aroD基因，与亲本菌株福氏志贺菌2457T相比，其在HeLa细胞内的生长显著减少。在5周内给8只食蟹猴口服接种四剂1×10¹¹个活细菌，福氏志贺菌SFL1070未产生不良反应，而福氏志贺菌2457T在所有8只未接种的猴子中均引起痢疾。因此，芳香族氨基酸依赖性使福氏志贺菌SFL1070显著减毒（p = 0.00008）。在8只接种疫苗的猴子中有7只（p < 0.01）在用SFL1070接种四剂后出现了显著的肠道福氏志贺菌脂多糖（LPS）特异性分泌型IgA反应。然而，在8只接种疫苗的猴子中只有4只出现了针对各种福氏志贺菌LPS抗原和侵袭质粒抗原（Ipa-s）的血清IgG或IgA反应。针对福氏志贺菌Y和2a LPS的血清IgG滴度升高达到显著水平（p ≤ 0.05）。在最后一次接种后2周，除1只猴子外，所有接种疫苗的猴子均受到保护，免受1×10¹⁰或1×10¹¹个福氏志贺菌2457T活菌的口服攻击。这种保护作用非常显著（p = 0.0007），因为所有接受等量2457T菌株攻击的未接种猴子均出现痢疾。其中3只死亡。对接种疫苗的猴子进行攻击感染后，3只猴子各自出现了针对同源福氏志贺菌2a LPS的血清IgA和IgG反应（0.005 ≤ p ≤ 0.025）。分别在5只和4只猴子中观察到针对Ipa-s的血清IgA和IgG反应（0.01 < p ≤ 0.05）。（摘要截断于250字）
