Macaque dendritic cells infected with SIV-recombinant canarypox ex vivo induce SIV-specific immune responses in vivo.
Dendritic cells (DCs) infected with recombinant avipox vectors express the introduced genes and activate antigen-specific T cells. DCs exhibit distinct differentiation-dependent immune functions. Moreover, immature DCs are readily infected by canarypox vectors, but undergo tumor necrosis factor (TNF)-alpha-dependent death, while fewer mature DCs get infected and resist dying. A pilot study was performed using the rhesus macaque system to explore whether immature and mature DCs infected with SIV-recombinant canarypox (vCP180) ex vivo could induce primary virus-specific immune responses in vivo. After subcutaneous (sc) reinjection, functional monocyte-derived DCs migrated to lymph nodes (LNs) within 1-2 days and primed T cells in vivo. This was observed by monitoring dye-labeled DCs in the draining LNs and tetanus toxoid (TT)-specific T cell responses after injection of TT-loaded DCs. DCs from simian immunodeficiency virus (SIV)-naïve rhesus macaques were infected with vCP180 (SIVmac142 gag, pol, and env genes), and sc reinjected into donor animals. Low-level SIV-specific T cell proliferation, but little if any interferon (IFN)-gamma production was detected. DCs pulsed with vCP180 in combination with TT and keyhole limpet hemocyanin (KLH) (to activate additional T cells and provide "helper" cytokines) induced SIV-, TT-, and KLH-specific T cell responses, including IFN-gamma responses not seen when vCP180-carrying DCs were used alone. Interleukin (IL)-10 and low-level antibody responses were also observed. This pilot study provides the proof of principle that sc injected ex vivo SIV-recombinant canarypox-infected DCs safely induce low-level SIV-specific immune responses in vivo.
Center for Biomedical Research, Population Council, New York, New York 10021, USA.
L
L
Villamide-Herrera
R
R
Ignatius
M A
MA
Eller
K
K
Wilkinson
C
C
Griffin
E
E
Mehlhop
J
J
Jones
S Y
SY
Han
M G
MG
Lewis
S
S
Parrish
T C
TC
Vancott
J D
JD
Lifson
S
S
Schlesinger
J R
JR
Mascola
M
M
Pope
D000818:Animals; D028121:Canarypox virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005822:Genetic Vectors; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology; D014614:Vaccines, Synthetic
D014614:Vaccines, Synthetic