title: 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.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK. tomas.hanke@imm.ox.ac.uk
authors.forename: Tomás
authors.initials: T
authors.lastname: Hanke
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dennis
authors.forename: Sally A
authors.initials: SA
authors.lastname: Sharpe
authors.forename: Lindsey A J
authors.initials: LA
authors.lastname: Powell
authors.forename: Lorraine
authors.initials: L
authors.lastname: McLoughlin
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Crome
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects / Q000493:pharmacokinetics*; D000818:Animals; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005822:Genetic Vectors / Q000235:genetics; D007271:Injections, Intradermal; D008251:Macaca; D051379:Mice; D016513:Mice, SCID; D016511:Severe Combined Immunodeficiency / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D019444:Vaccines, DNA; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D016915:AIDS Vaccines; D004279:DNA, Viral; C505104:MVA-HIVA vaccine; D019444:Vaccines, DNA