通过DNA免疫接种给予痘苗病毒包膜蛋白在保护BALB/c小鼠免受致死性鼻内痘病毒攻击中的差异功效。

Differential efficacy of vaccinia virus envelope proteins administered by DNA immunisation in protection of BALB/c mice from a lethal intranasal poxvirus challenge.

作者信息

Pulford D J, Gates A, Bridge S H, Robinson J H, Ulaeto D

机构信息

Biomedical Sciences, Dstl Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.

出版信息

Vaccine. 2004 Sep 3;22(25-26):3358-66. doi: 10.1016/j.vaccine.2004.02.034.

DOI:10.1016/j.vaccine.2004.02.034

PMID:15308360

Abstract

DNA vaccines might offer an alternative to the live smallpox vaccine in providing protective efficacy in an orthopoxvirus (OPV) lethal respiratory challenge model. BALB/c mice were immunised with DNA vaccines coding for 10 different single vaccinia virus (VACV) membrane proteins. After an intranasal challenge with the VACV IHD strain, three gene candidates B5R, A33R and A27L produced > or =66% survival. The B5R DNA vaccine consistently produced 100% protection and exhibited greatest efficacy after three 50 microg intramuscular doses in this model. Sero-conversion to these vaccines was often inconsistent, implying that antibody itself was not a correlate of protection. The B5R DNA vaccine induced a strong and consistent gamma interferon (IFNgamma) response in BALB/c mice given a single DNA vaccine dose. Strong IFNgamma responses were also measured in pTB5R immunised C57BL6 mice deficient for MHC class I molecules, suggesting that the memory response was mediated by a CD4+ T cell population.

摘要

在正痘病毒（OPV）致死性呼吸道攻击模型中，DNA疫苗可能在提供保护效力方面成为活天花疫苗的一种替代选择。用编码10种不同单一痘苗病毒（VACV）膜蛋白的DNA疫苗对BALB/c小鼠进行免疫。在用VACV IHD毒株进行鼻内攻击后，三种基因候选物B5R、A33R和A27L产生了≥66%的存活率。在该模型中，B5R DNA疫苗始终产生100%的保护效果，且在三次50微克肌肉注射剂量后表现出最大效力。针对这些疫苗的血清转化往往不一致，这意味着抗体本身并非保护的相关因素。给予单次DNA疫苗剂量后，B5R DNA疫苗在BALB/c小鼠中诱导了强烈且一致的γ干扰素（IFNγ）反应。在缺乏MHC I类分子的pTB5R免疫的C57BL6小鼠中也检测到了强烈的IFNγ反应，这表明记忆反应是由CD4 + T细胞群体介导的。