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

Abstract

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.

• Authors: Tomás Hanke, Andrew J McMichael, Michael J Dennis, Sally A Sharpe, Lindsey A J Powell, Lorraine McLoughlin, Steven J Crome
• Journal: Vaccine (Vaccine) Vol. 23 Issue 12 Pg. 1507-14 (Feb 10 2005) ISSN: 0264-410X [Print] Netherlands
• PMID: 15670887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AIDS Vaccines
• DNA, Viral
• MVA-HIVA vaccine
• Vaccines, DNA

Topics

• AIDS Vaccines (adverse effects, pharmacokinetics)
• Animals
• DNA, Viral (analysis)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Genetic Vectors (genetics)
• Injections, Intradermal
• Macaca
• Mice
• Mice, SCID
• Severe Combined Immunodeficiency (immunology)
• Simian Acquired Immunodeficiency Syndrome (immunology)
• Vaccines, DNA
• Vaccinia virus (genetics)