METACLIPSE THERAPEUTICS CORP — Department of Health and Human Services SBIR Phase II: 43

Description

Interleukin-12 (IL-12) and granulocyte macrophage colony-stimulating factor (GM-CSF) are endogenous immune activators. Earlier studies using soluble IL-12 and GM-CSF as vaccine adjuvants were unsuccessful due to toxicity or suboptimal response. We developed versions of IL-12 and GM-CSF with a glycosylated phosphatidylinositol (GPI) anchor added at the carboxyl terminus, allowing incorporation into lipid bilayers such as in influenza virus-like particles (VLPs). Previous studies in young and aged mice using GPI-GM-CSF and GPI-IL-12 incorporated influenza H1 VLPs induced strong humoral and cellular immunity that protected both young and aged mice from homologous and heterologous viral challenge. Currently, elderly patients fail to respond well to influenza vaccines. In this phase II proposal we will evaluate dose response and dose scheduling of the GPl-cytokine incorporated VLPs to determine the minimum anticipated biological effect level (MABEL) dose to induce a protective immune response in mice. This proposal will also evaluate the safety of the vaccine in murine and monkey models. Benchmarks required for cGMP-compliant vaccine production and characterization will also be determined. This study will contribute to the development of safe and effective adjuvant combinations that can be used to enhance the efficacy of influenza and other antiviral vaccines critically needed for the elderly.