Development of Membrane Anchored Cytokines as Novel Vaccine Adjuvants for the Elderly

lnterleukinILand granulocyte macrophage colony stimulating factorGM CSFare endogenous immune activatorsEarlier studies using soluble ILand GM CSF as vaccine adjuvants were unsuccessful due to toxicity or suboptimal responseWe developed versions of ILand GM CSF with a glycosylated phosphatidylinositolGPIanchor added at the carboxyl terminusallowing incorporation into lipid bilayers such as in influenza virus like particlesVLPsPrevious studies in young and aged mice using GPI GM CSF and GPI ILincorporated influenza HVLPs induced strong humoral and cellular immunity that protected both young and aged mice from homologous and heterologous viral challengeCurrentlyelderly patients fail to respond well to influenza vaccinesIn 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 levelMABELdose to induce a protective immune response in miceThis proposal will also evaluate the safety of the vaccine in murine and monkey modelsBenchmarks required for cGMP compliant vaccine production and characterization will also be determinedThis 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