Gogev Sacha, Vanderheijden Nathalie, Lemaire Myle'ne, Schynts Frédéric, D'Offay Jean, Deprez Isabelle, Adam Micheline, Eloit Marc, Thiry Etienne
Laboratory of Virology, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, University of Lie'ge, Boulevard de Colonster, 20-B 43 bis, 4000, Sart Tilman-Lie'ge, Belgium.
Vaccine. 2002 Jan 31;20(9-10):1451-65. doi: 10.1016/s0264-410x(01)00458-3.
Replication-defective human adenoviruses type 5 (HAd5) expressing the bovine herpesvirus type 1 (BHV-1) glycoprotein gC or gD under the control of the human cytomegalovirus immediate-early promoter/enhancer (AdCMVgC or AdCMVgD) or the 5' regulatory region of the human desmin gene (AdDESMgC or AdDESMgD) were generated. A preliminary experiment performed on rabbits showed that the intranasal administration of AdCMV elicited higher levels of BHV-1 neutralizing antibodies than the intramuscular administration of AdDESM. The obtained results allowed to select the replication-defective AdCMVgC and AdCMVgD for further assessment of their potential as a recombinant vaccine in cattle. Calves were injected intranasally twice 3 weeks apart with either AdCMVgC or AdCMVgD or a combination of these two recombinants or a commercially available live vaccine for comparison. The highest BHV-1 neutralizing antibody titres were obtained with AdCMVgD followed by the live vaccine and to a lower extent with the combination of the two recombinants (AdCMVgC+AdCMVgD). Calves were protected against intranasal BHV-1 challenge performed 3 weeks after the second immunization. In view of the obtained results, recombinant HAd5 may be developed as an intranasal vaccine vector in cattle administrated either alone or sequentially with non-human adenovirus-based vectors.
构建了在人巨细胞病毒立即早期启动子/增强子(AdCMVgC或AdCMVgD)或人结蛋白基因的5'调控区(AdDESMgC或AdDESMgD)控制下表达牛疱疹病毒1型(BHV-1)糖蛋白gC或gD的复制缺陷型人5型腺病毒(HAd5)。在兔子身上进行的一项初步实验表明,鼻内接种AdCMV诱导产生的BHV-1中和抗体水平高于肌肉注射AdDESM。所获结果使得能够选择复制缺陷型AdCMVgC和AdCMVgD,以进一步评估它们作为牛重组疫苗的潜力。给犊牛鼻内注射AdCMVgC或AdCMVgD或这两种重组体的组合,或者一种市售活疫苗,间隔3周注射两次用于比较。AdCMVgD诱导产生的BHV-1中和抗体滴度最高,其次是活疫苗,两种重组体组合(AdCMVgC + AdCMVgD)诱导产生的中和抗体滴度较低。在第二次免疫后3周对犊牛进行鼻内BHV-1攻毒时,犊牛受到了保护。鉴于所获结果,重组HAd5可开发成一种用于牛的鼻内疫苗载体,可单独使用,也可与基于非人腺病毒的载体序贯使用。