Therapeutic vaccination with simian immunodeficiency virus (SIV)-DNA + IL-12 or IL-15 induces distinct CD8 memory subsets in SIV-infected macaques.
DNA vaccination is an invaluable approach for immune therapy in that it lacks vector interference and thus permits repeated vaccination boosts. However, by themselves, DNA-based vaccines are typically poor inducers of Ag-specific immunity in humans and non-human primates. Cytokines, such as IL-12 and IL-15, have been shown to be potent adjuvants for the induction and maintenance of cellular immune responses, in particular during HIV infection. In this study, we examined the ability of therapeutic vaccination with SIV-DNA+IL-12 or IL-15 as molecular adjuvants to improve DNA vaccine potency and to enhance memory immune responses in SIV-infected macaques. Our results demonstrate that incorporating IL-12 into the vaccine induces SIV-specific CD8 effector memory T cell (T(EM)) functional responses and enhances the capacity of IFN-gamma-producing CD8 T(EM) cells to produce TNF. Lower levels of PD-1 were expressed on T cells acquiring dual function upon vaccination as compared with mono-functional CD8 T(EM) cells. Finally, a boost with SIV-DNA+IL-15 triggered most T cell memory subsets in macaques primed with either DNA-SIV or placebo but only CD8 T(EM) in macaques primed with SIV-DNA+IL-12. These results indicate that plasmid IL-12 and IL-15 cytokines represent a significant addition to enhance the ability of therapeutic DNA vaccines to induce better immunity.
Laboratoire d'Immunologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal Saint-Luc, Montréal, Québec, Canada.
Rabih
R
Halwani
Jean D
JD
Boyer
Bader
B
Yassine-Diab
Elias K
EK
Haddad
Tara M
TM
Robinson
Sanjeev
S
Kumar
Rose
R
Parkinson
Ling
L
Wu
Maninder K
MK
Sidhu
Rebecca
R
Phillipson-Weiner
George N
GN
Pavlakis
Barbara K
BK
Felber
Mark G
MG
Lewis
Anding
A
Shen
Robert F
RF
Siliciano
David B
DB
Weiner
Rafick-Pierre
RP
Sekaly
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000627:therapeutic use; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D019409:Interleukin-15 / Q000276:immunology* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D010957:Plasmids / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D015854:Up-Regulation / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D004279:DNA, Viral; D019409:Interleukin-15; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D018664:Interleukin-12; D007371:Interferon-gamma