Enhancement of non-specific antiviral immunity induced by mucosal administration of immunoadijivant in infant animal

免疫佐剂粘膜给药增强幼年动物非特异性抗病毒免疫力

• 批准号: 06454716
• 负责人: ARIKAWA Jiro
• 金额: $ 4.61万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06454716/
• 关键词: Influenzavirus; Rotavirus; Hantavirus; Adjuvant; MDP; Pseudorabies; Mucosal immunity; Animal experiment; インフルエンザウイルス; ウイルス感染

1. Animal models for studying respiratory infection, enteric infection and systemic infections were established by using mice and Sendai virus, rotavirus and hantavirus, respectively.2. MDP-Lys (L18) was selected as a immunoadjuvant and examined its effect on the enhancement of protection from infection after its administration by oral, intranasal, intrarectal and subcutaneous routes.3. Fatal Sendai virus infection was significantly reduced by administration of MDP-Lys (L18) through intranasal, ora and even intra rectal route.4. Rota virus diarrhea was significantly reduced by administration of MDP-Lys (L18) through subcutaneous, oral and intrarectal route.5. Fatal hantavirus infection was significantly reduced only by the administration of MDP-Lys (L18) through subcutaneous route.These results suggested the effect of immunoadjuvant on the augmentation of host immunity by common mucosa immune system. Further studies concerning to the quantitative estimation of the augmentation of host immunity. In addition, enhancement of specific immunity against vaccine antigen by the combination of the immunoadjuvant and mucosal administration should be studied.

1.分别用仙台病毒、轮状病毒和汉坦病毒建立小鼠呼吸道感染、肠道感染和全身感染的动物模型。选择MDP-Lys(L18)作为免疫佐剂，考察其经口、鼻腔、直肠和皮下给药后对感染的增强保护作用。MDP-Lys(L18)经鼻腔、口腔甚至直肠途径给药，可显著降低致死性仙台病毒感染。MDP-Lys(L18)皮下、口服和直肠给药可显著减轻轮状病毒腹泻小鼠的腹泻症状。只有皮下注射MDP-Lys(L18)才能显著降低致死性汉坦病毒感染，提示免疫佐剂对普通黏膜免疫系统增强宿主免疫有一定作用。关于宿主免疫增强的定量估计的进一步研究。此外，免疫佐剂与粘膜给药相结合，增强对疫苗抗原的特异性免疫作用也值得研究。

项目成果

Fukushima,A.: "Effect of MDP-Lys (L18) as a mucosal immunoadjuvant on protection of mucosal infections by Sendai virus and rotavirus" Vaccine. 14. 485-491 (1996)

Fukushima,A.：“MDP-Lys (L18) 作为粘膜免疫佐剂对保护仙台病毒和轮状病毒粘膜感染的作用”疫苗。

Taniguchi, K., Nishikawa, K., Kobayashi, N., Urasawa, T., Wu, H., Gorziglia, M.and Urasawa, S.: "Differences in plaque size and VP4 sequence found in SA11 virus clones having simian authentic VP4." Virology. 198. 325-330 (1994)

Taniguchi, K.、Nishikawa, K.、Kobayashi, N.、Urasawa, T.、Wu, H.、Gorziglia, M.和 Urasawa, S.：“在具有猿猴的 SA11 病毒克隆中发现的噬斑大小和 VP4 序列的差异

Yoshida,R.: "Effect of synthetic lipid A-related compound,DT-5461,on resistance to Sendai virus infection in mice" Immunopharmacology. 28. 153-161 (1994)

Yoshida,R.：“合成脂质 A 相关化合物 DT-5461 对小鼠抵抗仙台病毒感染的影响”免疫药理学。

Takada,A.: "Protective immune response of chickens against Newcastle disease, induced by the intranasal vaccination with inactivated virus." Veterinary Microbiology. 50. 17-25 (1996)

Takada,A.：“通过鼻内接种灭活病毒诱导鸡对新城疫的保护性免疫反应。”

Taniguchi,K.: "Nondefective rotavirus mutants with an NSP1 gene which has a deletion of 500 nucleotides,including a cycteine-rich zinc finger motif-encoding region (nucleotides 156 to 248),or which has a nonsense codon at nucleotides 153 to 155." Journal

Taniguchi, K.：“带有 NSP1 基因的无缺陷轮状病毒突变体，该基因缺失了 500 个核苷酸，包括富含半胱氨酸的锌指基序编码区（核苷酸 156 至 248），或者在核苷酸 153 至 155 处具有无义密码子