NDLI: Functional Genomic and Serological Analysis of the Protective Immune Response Resulting from Vaccination of Macaques with an NS1-Truncated Influenza Virus▿

Content Provider	PubMed Central
Author	Baskin, C. R. Bielefeldt-ohmann, H. García-sastre, A. Tumpey, T. M. Hoeven, N. Van Carter, V. S. Thomas, M. J. Proll, S. Solórzano, A. Billharz, R. Fornek, J. L. Thomas, S. Chen, C. H. Clark, E. A. Murali Krishna, Kaja Katze, M. G.
Abstract	We are still inadequately prepared for an influenza pandemic due to the lack of a vaccine effective for subtypes to which the majority of the human population has no prior immunity and which could be produced rapidly in sufficient quantities. There is therefore an urgent need to investigate novel vaccination approaches. Using a combination of genomic and traditional tools, this study compares the protective efficacy in macaques of an intrarespiratory live influenza virus vaccine produced by truncating NS1 in the human influenza A/Texas/36/91 (H1N1) virus with that of a conventional vaccine based on formalin-killed whole virus. After homologous challenge, animals in the live-vaccine group had greatly reduced viral replication and pathology in lungs and reduced upper respiratory inflammation. They also had lesser induction of innate immune pathways in lungs and of interferon-sensitive genes in bronchial epithelium. This postchallenge response contrasted with that shortly after vaccination, when more expression of interferon-sensitive genes was observed in bronchial cells from the live-vaccine group. This suggested induction of a strong innate immune response shortly after vaccination with the NS1-truncated virus, followed by greater maturity of the postchallenge immune response, as demonstrated with robust influenza virus-specific CD4+ T-cell proliferation, immunoglobulin G production, and transcriptional induction of T- and B-cell pathways in lung tissue. In conclusion, a single respiratory tract inoculation with an NS1-truncated influenza virus was effective in protecting nonhuman primates from homologous challenge. This protection was achieved in the absence of significant or long-lasting adverse effects and through induction of a robust adaptive immune response.
Related Links	http://dx.doi.org/10.1128/JVI.00590-07
Starting Page	11817
File Format	PDF
ISSN	10985514
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	21
Volume Number	81
Language	English
Publisher	American Society for Microbiology (ASM)
Publisher Date	2007-11-01
Access Restriction	Open
Rights Holder	American Society for Microbiology (ASM)
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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