Biodistribution and persistence of an MVA-vectored candidate HIV vaccine in SIV-infected rhesus macaques and SCID mice

被引:34
作者
Hanke, T [1 ]
McMichael, AJ
Dennis, MJ
Sharpe, SA
Powell, LAJ
McLoughlin, L
Crome, SJ
机构
[1] Weatherall Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
[2] Hlth Protect Agcy, Ctr Appl Microbiol & Res, Salisbury SP4 0JG, Wilts, England
[3] Huntington Life Sci, Huntingdon PE28 4HS, England
基金
英国医学研究理事会;
关键词
biodistribution; HIV vaccine; MVA-HIVA;
D O I
10.1016/j.vaccine.2004.08.050
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Recombinant modified vaccinia virus Ankara (MVA) is together with a few other attenuated viral vectors on the forefront of human immunodeficiency virus type 1 (HIV-1) vaccine development. As such, MVA-vectored vaccines are likely to be administered into immuno-compromized individuals. Here, we demonstrated in a good laboratory practice study safety and biological clearance of candidate HIV-1 vaccine MVA-HIVA in simian immunodeficiency virus (SIV)-infected rhesus macaques and mice with a severe combined immunodeficiency (SCID) following an intradermal vaccine administration. In SIV-infected macaques, MVA-HIVA DNA was undetectable by nested PCR 6 weeks after dosing. In SCID mice, the MVA-HIVA vaccine was well tolerated and a positive PCR signal was only observed at the site of injection 49 days after dosing in four out of six mice, but even these sites were negative by day 81 post-injection. Therefore, the MVA-HIVA vaccine is considered safe for application in phase I clinical trials in HIV-1-infected human subjects. These results also contribute to the confidence of using MVA as a smallpox vaccine. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1507 / 1514
页数:8
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