Title:

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

Authors:

Jean D. Boyer*, Tara M. Robinson*, Michele A. Kutzler*, Gordon Vansant^†, David A. Hokey*, Sanjeev Kumar*, Rose Parkinson*, Ling Wu*, Maninder K. Sidhu^‡, George N. Pavlakis§, Barbara K. Felber^§, Charles Brown^¶, Peter Silvera, Mark G. Lewis**, Joseph Monforte^†, Thomas A. Waldmann^††‡‡, John Eldridge^‡, and David B. Weiner*^‡‡

*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

Source:

Year:

2007 Nov; Volume: 104 (47)  Pages: 18648–18653

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--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- was up-upregulated 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.