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: Edgar Turner Overton, Jack Stapleton, Ian Frank, Shawn Hassler, Paul A Goepfert, David Barker, Eva Wagner, Alfred von Krempelhuber, Garth Virgin, Thomas Peter Meyer, Jutta Müller, Nicole Bädeker, Robert Grünert, Philip Young, Siegfried Rösch, Jane Maclennan, Nathaly Arndtz-Wiedemann, Paul Chaplin
• Journal: Open forum infectious diseases (Open Forum Infect Dis) Vol. 2 Issue 2 Pg. ofv040 (Apr 2015) ISSN: 2328-8957 [Print] United States
• PMID: 26380340 (Publication Type: Journal Article)