SAFETY AND IMMUNOGENICITY OF A PROTOTYPE ORAL WHOLE-CELL KILLED CAMPYLOBACTER VACCINE ADMINISTERED WITH A MUCOSAL ADJUVANT IN NONHUMAN-PRIMATES
SAFETY AND IMMUNOGENICITY OF A PROTOTYPE ORAL WHOLE-CELL KILLED CAMPYLOBACTER VACCINE ADMINISTERED WITH A MUCOSAL ADJUVANT IN NONHUMAN-PRIMATES
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DOI：
10.1016/0264-410x(95)80006-y
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发表时间：
1995-01-01
期刊：
影响因子：
5.5
通讯作者：
PAVLOVSKIS, OR
中科院分区：
文献类型：
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作者：
BAQAR, S;BOURGEOIS, AL;PAVLOVSKIS, OR
在恒河猴身上测试了两种原型口服弯曲杆菌全细胞杀伤疫苗的安全性和免疫原性。动物接种两剂疫苗（第0天和第14天），疫苗由CWC（10（10）粒/剂）单独或与0.5-1000 μ g大肠杆菌热不稳定肠毒素作为口服佐剂（OA）联合接种。初次免疫后4周，对单独接种CWC或补充0.5、5或50 μ g OA的动物进行加强接种。CWC和CWC- oa均具有良好的耐受性，无不良副作用，在每次疫苗剂量后7天收集的外周血中检测弯曲杆菌特异性和佐剂特异性抗体分泌细胞（ASCs）。OA可增强弯曲杆菌特异性IgA ASC反应，且呈剂量依赖性（p = 0.025），而IgG ASC反应则无此作用。在接种佐剂疫苗的猴子中，弯曲杆菌抗原的血清转化（IgA和IgG）也增强了，在任何免疫组的循环ASCs中都没有观察到明显的加强疫苗接种效果。体外t细胞对空肠弯曲杆菌抗原的增殖反应在CWC和CWC- oa免疫组都有所增强。这些结果表明，CWC- oa在灵长类动物中刺激局部和全身弯曲杆菌特异性IgA和IgG反应的能力是安全的，优于单独CWC，并支持其在人类临床研究中的进一步评估。
The safety and immunogenicity of two prototype oral Campylobacter killed whole-cell (CWC) vaccines were tested in rhesus monkeys. Animals were immunized with a primary two-dose ser ies (days 0 and 14) of vaccine consisting of CWC (10(10) particles/dose) given alone or in combination with 0.5-1000 mu g of the heat-labile enterotoxin of Escherichia coli as an oral adjuvant (OA). A booster vaccination, 4 weeks after primary immunization, was given to animals receiving CWC alone or supplemented with 0.5, 5 or 50 mu g of OA. Both CWC and CWC-OA were well tolerated with no adverse side-effects noted Campylobacter-specific as well as adjuvant-specific antibody-secreting cells (ASCs) were determined in peripheral blood collected 7 days after each vaccine dose. Campylobacter-specific IgA ASC responses were enhanced by OA in a dose-dependent manner (p = 0.025), while IgG ASC responses were not. Seroconversions (both IgA and IgG) to Campylobacter antigens were also enhanced in monkeys receiving adjuvanted vaccine, No significant booster vaccination effect was observed in circulating ASCs in any of the immunization groups. In vitro T-cell proliferative responses to Campylobacter jejuni antigens were somewhat enhanced in both the CWC and CWC-OA immunization groups. These results demonstrate that CWC-OA is safe and superior to CWC alone in its ability to stimulate both local and systemic Campylobacter-specific IgA and IgG responses in primates and they support its further evaluation in human clinical studies.