Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

doi:10.1073/pnas.0709198104

Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

*Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104;
^†Genomix, Althea Technologies Inc., San Diego, CA 92121;
^‡Vaccine Discovery, Wyeth, Pearl River, NY 10965;
^§Vaccine Branch, National Cancer Institute, Building 535, Room 210, Frederick, MD 21702;
^¶Viral Pathogenesis and Vaccine Branch, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892;
^‖Life Sciences Division, Southern Research Institute (SRI), Frederick, MD 21701;
**Research Section, Bioqual, Rockville, MD 20850; and
^††Metabolism Branch, National Cancer Institute, Building 10, Room 4N115, Frederick, MD 21702

Contributed by Thomas A. Waldmann, September 28, 2007 (received for review May 15, 2007)

Abstract

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-γ-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-γ 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.

Footnotes

^‡‡To whom correspondence may be addressed. E-mail: dbweiner{at}mail.med.upenn.edu or tawald{at}helix.nih.gov
Author contributions: J.D.B. and D.B.W. designed research; T.M.R., G.V., D.A.H., S.K., R.P., L.W., C.B., P.S., and M.G.L. performed research; M.A.K., S.K., M.K.S., G.N.P., B.K.F., J.M., and J.E. contributed new reagents/analytic tools; and J.D.B., T.A.W., and D.B.W. wrote the paper.
The authors declare no conflict of interest.
Abbreviations:

SHIV,

simian/human immunodeficiency virus;

SIV,

simian imunodeficiency virus;

PBMC,

peripheral blood mononuclear cell;

ELISpot,

ELISA-linked immunospot;

SFC,

spot-forming cells;

MID,

monkey infectious doses.