Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid.
The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-gamma-producing CD8(+) and CD4(+) effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-gamma was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication.
Boyer
Jean D
JD
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
Robinson
Tara M
TM
Kutzler
Michele A
MA
Vansant
Gordon
G
Hokey
David A
DA
Kumar
Sanjeev
S
Parkinson
Rose
R
Wu
Ling
L
Sidhu
Maninder K
MK
Pavlakis
George N
GN
Felber
Barbara K
BK
Brown
Charles
C
Silvera
Peter
P
Lewis
Mark G
MG
Monforte
Joseph
J
Waldmann
Thomas A
TA
Eldridge
John
J
Weiner
David B
DB
D000818:Animals; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D015683:Gene Products, gag / Q000276:immunology; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008251:Macaca / Q000276:immunology*; D010957:Plasmids / Q000235:genetics*; D012191:Retroviridae Proteins / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014779:Virus Replication
D015683:Gene Products, gag; D019409:Interleukin-15; D012191:Retroviridae Proteins; D007371:Interferon-gamma