Membrane-bound SIV envelope trimers are immunogenic in ferrets after intranasal vaccination with a replication-competent canine distemper virus vector

详细信息    查看全文

• 作者：Xinsheng Zhang ; Olivia Wallace ; Kevin J. Wright ; Martin Backer ; John W. Coleman ; Rebecca Koehnke ; Esther Frenk ; Arban Domi ; Maria J. Chiuchiolo ; Joanne DeStefano ; S ; eep Narpala ; Rebecca Powell ; Gavin Morrow ; Cesar Boggiano ; Timothy J. Zamb ; C. Richter King ; Christopher L. Parks
• 关键词：Canine distemper virus ; Human immunodeficiency virus ; Simian immunodeficiency virus ; Envelope ; Replicating viral vector ; Immunogen ; Ferret
• 刊名：Virology
• 出版年：2013
• 出版时间：November, 2013
• 年：2013
• 卷：446
• 期：1-2
• 页码：25-36
• 全文大小：9675 K

文摘

We are investigating canine distemper virus (CDV) as a vaccine vector for the delivery of HIV envelope (Env) that closely resembles the native trimeric spike. We selected CDV because it will promote vaccine delivery to lymphoid tissues, and because human exposure is infrequent, reducing potential effects of pre-existing immunity. Using SIV Env as a model, we tested a number of vector and gene insert designs. Vectors containing a gene inserted between the CDV H and L genes, which encoded Env lacking most of its cytoplasmic tail, propagated efficiently in Vero cells, expressed the immunogen on the cell surface, and incorporated the SIV glycoprotein into progeny virus particles. When ferrets were vaccinated intranasally, there were no signs of distress, vector replication was observed in the gut-associated lymphoid tissues, and the animals produced anti-SIV Env antibodies. These data show that live CDV-SIV Env vectors can safely induce anti-Env immune responses following intranasal vaccination.