4.5 Article

Immunization of knock-out α/β interferon receptor mice against lethal bluetongue infection with a BoHV-4-based vector expressing BTV-8 VP2 antigen

期刊

VACCINE
卷 29, 期 16, 页码 3074-3082

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2011.01.075

关键词

Viral vector; Bovine herpesvirus 4; BTV; VP2

资金

  1. Italian Ministry of University and Scientific Research (Italian National Grant MIUR)
  2. Fondazione Cariparma (Cassa di Risparmio di Parma, Italy)
  3. Comision Interministerial de Ciencia y Tecnologia (CICYT) [AGL2008-00646/GAN]
  4. EU Network of Excellence EPIZONE [FOOD-CT-2006-016236]

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New effective tools for vaccine strategies are necessary to limit the spread of bluetongue, an insect-transmitted viral disease of domestic and wild ruminants. In the present study. BoHV-4-based vector cloned as a bacterial artificial chromosome (BAC) was engineered to express the bluetongue virus (BTV) immune-dominant glycoprotein VP2 provided of a heterologous signal peptide to its amino terminal and a trans-membrane domain to its carboxyl terminal (IgK-VP2gDtm), to allow the VP2 expression targeting to the cell membrane fraction. Based on adult alpha/beta interferon receptor knockout (IFNAR((-/-))) mice, a newly generated bluetongue laboratory animal model, a pre-challenge experiment was performed to test BoHV-4 safety on such immune-compromised animal. BoHV-4 infected IFNAR((-/-)) mice did not show clinical signs even following the inoculation of BoHV-4 intra-cerebrally, although many areas of the brain got transduced. IFNAR((-/-)) mice intraperitoneally inoculated twice with BoHV-4-A-IgK-VP2gDtm at different time points developed serum neutralizing antibodies against BTV and showed a strongly reduced viremia and a longer survival time when challenged with a lethal dose of BTV-8. The data acquired in this pilot study validate BoHV-4-based vector as a safe and effective heterologous antigen carrier/producer for the formulation of enhanced recombinant immunogens for the vaccination against lethal bluetongue. (C) 2011 Elsevier Ltd. All rights reserved.

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