Characterisation of a live Salmonella vaccine stably expressing the Mycobacterium tuberculosis Ag85B-ESAT6 fusion protein.
Characterisation of a live Salmonella vaccine stably expressing the Mycobacterium tuberculosis Ag85B-ESAT6 fusion protein.
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DOI：
10.1016/j.vaccine.2009.09.007
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发表时间：
2009-11-16
期刊：
影响因子：
5.5
通讯作者：
Dougan G
中科院分区：
文献类型：
--
作者：
Hall LJ;Clare S;Pickard D;Clark SO;Kelly DL;El Ghany MA;Hale C;Dietrich J;Andersen P;Marsh PD;Dougan G
重组肠道沙门氏菌鼠伤寒血清型（S。构建了从染色体上稳定表达结核分枝杆菌融合抗原Ag 85 B-ESAT 6的疫苗株。用沙门氏菌/Ag 85 B-ESAT 6菌株对小鼠进行活的口服疫苗接种产生了有效的抗Ag 85 B-ESAT 6 TH 1应答，具有高抗体滴度和IgG 2a偏倚，并持续120天的显著IFN-γ产生。当用沙门氏菌/Ag 85 B-ESAT 6疫苗致敏的小鼠用Ag 85 B-ESAT 6抗原和佐剂粘膜加强时，IFN-γ应答显著增加。为了确定该疫苗株的保护效力，对豚鼠进行免疫接种，并在用M.结核活沙门氏菌疫苗的异源初免-加强策略，随后是抗原和佐剂的全身加强，降低了M。肺和脾脏中的结核菌数量与卡介苗相同。此外，观察到该疫苗接种方案在保护方面与BCG免疫接种在统计学上等效。因此，用重组沙门氏菌/Ag 85 B-ESAT 6进行活的口服初免并用Ag 85 B-ESAT 6加佐剂LTK 63进行加强代表了有效的粘膜接种方案。
A recombinant Salmonella enterica serovar Typhimurium (S. Typhimurium) vaccine strain was constructed that stably expressed the Mycobacterium tuberculosis fusion antigen Ag85B–ESAT6 from the chromosome. Live oral vaccination of mice with the Salmonella/Ag85B–ESAT6 strain generated a potent anti-Ag85B–ESAT6 TH1 response with high antibody titres with a IgG2a-bias and significant IFN-γ production lasting over a 120-day period. When mice primed with the Salmonella/Ag85B–ESAT6 vaccine were mucosally boosted with the Ag85B–ESAT6 antigen and adjuvant the IFN-γ responses increased markedly. To determine the protective efficacy of this vaccine strain, guinea pigs were immunised and followed for a 30-week period after aerosol challenge with M. tuberculosis. The heterologous prime-boost strategy of live Salmonella vaccine followed by a systemic boost of antigen and adjuvant reduced the levels of M. tuberculosis bacteria in the lungs and spleen to the same extent as BCG. Additionally, this vaccination regimen was observed to be statistically equivalent in terms of protection to immunisation with BCG. Thus, live oral priming with the recombinant Salmonella/Ag85B–ESAT6 and boosting with Ag85B–ESAT6 plus the adjuvant LTK63 represents an effective mucosal vaccination regimen.
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影响因子：
3.1
作者：
Doherty, TM;Olsen, AW;Andersen, P
通讯作者：
Andersen, P
影响因子：
4.4
作者：
Dietrich, Jes;Andersen, Claire;Andersen, Peter
通讯作者：
Andersen, Peter
DOI：
10.1111/j.1574-695x.2000.tb01440.x
发表时间：
2000-04-01
影响因子：
--
作者：
Allen, JS;Dougan, G;Strugnell, RA
通讯作者：
Strugnell, RA
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
影响因子：
3.1
作者：
HSU, HS;MAYO, DR
通讯作者：
MAYO, DR