Membrane-bound SIV envelope trimers are immunogenic in ferrets after intranasal vaccination with a replication-competent canine distemper virus vector.
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.
AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY, USA; Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY, USA. Electronic address: xzhang@iavi.org.
Xinsheng
X
Zhang
Olivia
O
Wallace
Kevin J
KJ
Wright
Martin
M
Backer
John W
JW
Coleman
Rebecca
R
Koehnke
Esther
E
Frenk
Arban
A
Domi
Maria J
MJ
Chiuchiolo
Joanne
J
DeStefano
Sandeep
S
Narpala
Rebecca
R
Powell
Gavin
G
Morrow
Cesar
C
Boggiano
Timothy J
TJ
Zamb
C
C
Richter King
Christopher L
CL
Parks
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004217:Distemper Virus, Canine / Q000235:genetics*; D004337:Drug Carriers; D005289:Ferrets; D041981:Gastrointestinal Tract / Q000821:virology; D008221:Lymphoid Tissue / Q000821:virology; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D004337:Drug Carriers; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins
Canine distemper virus; Envelope; Ferret; Human immunodeficiency virus; Immunogen; Replicating viral vector; Simian immunodeficiency virus