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

Abstract 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 pot...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2013-11, Vol.446 (1), p.25-36
Main Authors: Zhang, Xinsheng, Wallace, Olivia, Wright, Kevin J, Backer, Martin, Coleman, John W, Koehnke, Rebecca, Frenk, Esther, Domi, Arban, Chiuchiolo, Maria J, DeStefano, Joanne, Narpala, Sandeep, Powell, Rebecca, Morrow, Gavin, Boggiano, Cesar, Zamb, Timothy J, Richter King, C, Parks, Christopher L
Format: Article
Language:English
Subjects:
Administration, Intranasal
Animals
Antibodies, Viral - blood
Canine distemper virus
Distemper Virus, Canine - genetics
Drug Carriers
Envelope
Ferret
Ferrets
Gastrointestinal Tract - virology
Human immunodeficiency virus
Immunogen
Infectious Disease
Lymphoid Tissue - virology
Mustela
Replicating viral vector
SAIDS Vaccines - administration & dosage
SAIDS Vaccines - genetics
SAIDS Vaccines - immunology
Simian immunodeficiency virus
Simian Immunodeficiency Virus - genetics
Simian Immunodeficiency Virus - immunology
Vaccination - methods
Vaccines, Attenuated - administration & dosage
Vaccines, Attenuated - genetics
Vaccines, Attenuated - immunology
Viral Envelope Proteins - genetics
Viral Envelope Proteins - immunology
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Summary:Abstract 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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2013.07.012