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

• Published in: Vaccine 2005-02, Vol.23 (12), p.1507-1514
• Main Authors: Hanke, Tomáš, McMichael, Andrew J., Dennis, Michael J., Sharpe, Sally A., Powell, Lindsey A.J., McLoughlin, Lorraine, Crome, Steven J.
• Format: Article
• Language: English
• Subjects: AIDS Vaccines - adverse effects; AIDS Vaccines - pharmacokinetics; Animals; Applied microbiology; Biodistribution; Biological and medical sciences; Disease Models, Animal; DNA, Viral - analysis; Drug Evaluation, Preclinical; Fundamental and applied biological sciences. Psychology; Genetic Vectors - genetics; Good Manufacturing Practice; HIV; HIV vaccine; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Infectious diseases; Injection; Injections, Intradermal; Macaca; Macaca mulatta; Medical sciences; Mice; Mice, SCID; Microbiology; Miscellaneous; MVA·HIVA; Severe Combined Immunodeficiency - immunology; Simian Acquired Immunodeficiency Syndrome - immunology; Simian immunodeficiency virus; Smallpox; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccinia virus; Vaccinia virus - genetics; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2004.08.050

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 immunocompromized 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.