title: Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial.
abstract: Background.  First- and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness. The focus of this study was to compare the safety and immunogenicity of a replication-deficient, highly attenuated smallpox vaccine modified vaccinia Ankara (MVA) in HIV-infected and healthy subjects. Methods.  An open-label, controlled Phase II trial was conducted at 36 centers in the United States and Puerto Rico for HIV-infected and healthy subjects. Subjects received 2 doses of MVA administered 4 weeks apart. Safety was evaluated by assessment of adverse events, focused physical exams, electrocardiogram recordings, and safety laboratories. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). Results.  Five hundred seventy-nine subjects were vaccinated at least once and had data available for analysis. Rates of ELISA seropositivity were comparably high in vaccinia-naive healthy and HIV-infected subjects, whereas PRNT seropositivity rates were higher in healthy compared with HIV-infected subjects. Modified vaccinia Ankara was safe and well tolerated with no adverse impact on viral load or CD4 counts. There were no cases of myo-/pericarditis reported. Conclusions.  Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations.
authors.affiliation: Division of Infectious Diseases, University of Alabama at Birmingham, School of Medicine , Birmingham, Alabama.
authors.forename: Edgar Turner
authors.initials: ET
authors.lastname: Overton
authors.affiliation: Depts. of Internal Medicine, Microbiology & Immunology , University of Iowa , Iowa City.
authors.forename: Jack
authors.initials: J
authors.lastname: Stapleton
authors.affiliation: Infectious Diseases Section , University of Pennsylvania , Philadelphia.
authors.forename: Ian
authors.initials: I
authors.lastname: Frank
authors.affiliation: Optimus Medical Group , San Francisco, California.
authors.forename: Shawn
authors.initials: S
authors.lastname: Hassler
authors.affiliation: Division of Infectious Diseases, University of Alabama at Birmingham, School of Medicine , Birmingham, Alabama.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.affiliation: Core Center , Chicago, Illinois, USA.
authors.forename: David
authors.initials: D
authors.lastname: Barker
authors.affiliation: Bavarian Nordic, Martinsried.
authors.forename: Eva
authors.initials: E
authors.lastname: Wagner
authors.affiliation: GlaxoSmithKline GmbH & Co. KG , Munich, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: von Krempelhuber
authors.affiliation: Vifor Pharma Ltd , Glattbrugg, Switzerland.
authors.forename: Garth
authors.initials: G
authors.lastname: Virgin
authors.affiliation: Bavarian Nordic, Martinsried.
authors.forename: Thomas Peter
authors.initials: TP
authors.lastname: Meyer
authors.affiliation: Bavarian Nordic, Martinsried.
authors.forename: Jutta
authors.initials: J
authors.lastname: Müller
authors.affiliation: Bavarian Nordic, Martinsried.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bädeker
authors.affiliation: Bavarian Nordic, Martinsried.
authors.forename: Robert
authors.initials: R
authors.lastname: Grünert
authors.affiliation: Bavarian Nordic, Martinsried.
authors.forename: Philip
authors.initials: P
authors.lastname: Young
authors.affiliation: Bavarian Nordic, Martinsried.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Rösch
authors.affiliation: Bavarian Nordic, Martinsried.
authors.forename: Jane
authors.initials: J
authors.lastname: Maclennan
authors.affiliation: Bavarian Nordic, Martinsried.
authors.forename: Nathaly
authors.initials: N
authors.lastname: Arndtz-Wiedemann
authors.affiliation: Bavarian Nordic, Martinsried.
authors.forename: Paul
authors.initials: P
authors.lastname: Chaplin
keywords: HIV infection; MVA; immunocompromised; smallpox; vaccination