a pandemic influenza h1n1 live vaccine based on modified vaccinia ankara is highly immunogenic and protects mice in active and passive immunizations基于修改的h1n1大流行性流感活疫苗牛痘安卡拉高度免疫原性和保护老鼠在主动和被动免疫.pdfVIP

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2017-09-05 发布于上海
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a pandemic influenza h1n1 live vaccine based on modified vaccinia ankara is highly immunogenic and protects mice in active and passive immunizations基于修改的h1n1大流行性流感活疫苗牛痘安卡拉高度免疫原性和保护老鼠在主动和被动免疫.pdf

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a pandemic influenza h1n1 live vaccine based on modified vaccinia ankara is highly immunogenic and protects mice in active and passive immunizations基于修改的h1n1大流行性流感活疫苗牛痘安卡拉高度免疫原性和保护老鼠在主动和被动免疫

A Pandemic Influenza H1N1 Live Vaccine Based on Modified Vaccinia Ankara Is Highly Immunogenic and Protects Mice in Active and Passive Immunizations Annett Hessel, Michael Schwendinger, Daniela Fritz, Sogue Coulibaly, Georg W. Holzer, Nicolas Sabarth, Otfried Kistner, Walter Wodal, Astrid Kerschbaum, Helga Savidis-Dacho, Brian A. Crowe, Thomas R. Kreil, P. Noel Barrett, Falko G. Falkner* RD Vaccines, Biomedical Research Center, Baxter BioScience, Orth/Donau, Austria Abstract Background: The development of novel influenza vaccines inducing a broad immune response is an important objective. The aim of this study was to evaluate live vaccines which induce both strong humoral and cell-mediated immune responses against the novel human pandemic H1N1 influenza virus, and to show protection in a lethal animal challenge model. Methodology/Principal Findings: For this purpose, the hemagglutinin (HA) and neuraminidase (NA) genes of the influenza A/California/07/2009 (H1N1) strain (CA/07) were inserted into the replication-deficient modified vaccinia Ankara (MVA) virus - a safe poxviral live vector – resulting in MVA-H1-Ca and MVA-N1-Ca vectors. These live vaccines, together with an inactivated whole virus vaccine, were assessed in a lung infection model using immune competent Balb/c mice, and in a lethal challenge model using severe combined immunodeficient (SCID) mice after passive serum transfer from immunized mice. Balb/c mice vaccinated with the MVA-H1-Ca virus or the inactivated vaccine were fully protected from lung infection after challenge with the influenza H1N1 wild-type strain, while the neuraminidase virus MVA-N1-Ca induced only partial protection. The live vaccines were already protective after a single dose and induced substantial amounts of neutralizing antibodies and of interferon-c-secreting (IFN-c) CD4- and CD8 T-cells in lungs and spleens. In the lungs, a