Induction of cellular immune responses to simian immunodeficiency virus gag by two recombinant negative-strand RNA virus vectors.
A recombinant Newcastle disease virus (rNDV) expressing simian immunodeficiency virus (SIV) Gag protein (rNDV/SIVgag) was generated. The rNDV/SIVgag virus induced Gag-specific cellular immune responses in mice, leading to a specific anti-Gag antiviral immunity. This was evidenced by the inhibition of growth of recombinant vaccinia virus expressing an identical Gag antigen (rVac/SIVgag) but not of wild-type vaccinia virus in rNDV/SIVgag-immunized mice. Among intravenous, intraperitoneal, or intranasal immunization routes, intranasal administration induced the strongest protective response against challenge with rVac/SIVgag. We further demonstrated that these immune responses were greatly enhanced after booster immunization with recombinant influenza viruses expressing immunogenic portions of SIV Gag. The magnitude of the protective immune response correlated with the levels of cellular immune responses to Gag, which were still evident 9 weeks after immunization. These results suggest that rNDV and influenza virus vectors are suitable candidate vaccines against AIDS as well as against other infectious diseases.
Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Yurie
Y
Nakaya
Takaaki
T
Nakaya
Man-Seong
MS
Park
Jerome
J
Cros
Jiro
J
Imanishi
Peter
P
Palese
Adolfo
A
García-Sastre
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D005347:Fibroblasts; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000235:genetics*; D007111:Immunity, Cellular / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009522:Newcastle disease virus / Q000235:genetics*; D009975:Orthomyxoviridae / Q000235:genetics*; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics; D014709:Vero Cells; D014779:Virus Replication
D015683:Gene Products, gag; D018449:SAIDS Vaccines