用新型佐剂或明矾配制的恶性疟原虫 MSP1(42) 疟疾候选疫苗的临床前评估。
Pre-clinical evaluation of the malaria vaccine candidate P. falciparum MSP1(42) formulated with novel adjuvants or with alum.
作者信息
Pichyangkul Sathit, Gettayacamin Montip, Miller R Scott, Lyon Jeffrey A, Angov Evelina, Tongtawe Pongsri, Ruble David L, Heppner D Gray, Kester Kent E, Ballou W Ripley, Diggs Carter L, Voss Gerald, Cohen Joe D, Walsh Douglas S
机构信息
Department of Immunology and Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Bangkok, Thailand.
出版信息
Vaccine. 2004 Sep 28;22(29-30):3831-40. doi: 10.1016/j.vaccine.2004.07.023.
We compared the safety and immunogenicity of the recombinant Plasmodium falciparum MSP1(42) antigen formulated with four novel adjuvant systems (AS01B, AS02A, AS05 and AS08) to alum in rhesus monkeys. All five formulations of MSP1(42) were safe and immunogenic. Whereas, all MSP1(42) formulations tested generated high stimulation indices for lymphocyte proliferation (ranging from 27 to 50), the AS02A and AS01B formulations induced the highest levels of specific anti-MSP1(42) antibody. ELISPOT assays showed that the AS02A and AS01B vaccine formulations-induced different cytokine response profiles. Using the ratio of IFN-gamma/IL-5 secreting cells as the metric, the AS01B formulation induced a strong Th1 response, whereas the AS02A formulation induced a balanced Th1/Th2 response. The IFN-gamma response generated by AS02A and AS01B formulations persisted at least 24 weeks after final vaccination. The notable difference in Th1/Th2 polarization induced by the AS02A and AS01B formulations warrants comparative clinical testing.
我们在恒河猴中比较了用四种新型佐剂系统（AS01B、AS02A、AS05和AS08）配制的重组恶性疟原虫MSP1(42)抗原与明矾的安全性和免疫原性。MSP1(42)的所有五种制剂均安全且具有免疫原性。虽然所有测试的MSP1(42)制剂都产生了较高的淋巴细胞增殖刺激指数（范围为27至50），但AS02A和AS01B制剂诱导产生的特异性抗MSP1(42)抗体水平最高。ELISPOT分析表明，AS02A和AS01B疫苗制剂诱导了不同的细胞因子反应谱。以IFN-γ/IL-5分泌细胞的比例为指标，AS01B制剂诱导了强烈的Th1反应，而AS02A制剂诱导了平衡的Th1/Th2反应。AS02A和AS01B制剂产生的IFN-γ反应在最后一次接种后至少持续24周。AS02A和AS01B制剂诱导的Th1/Th2极化的显著差异值得进行比较临床试验。
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