Ebola virus: Development of Filovirus glycoprotein Fc fusion proteins as a vaccine candidate

Abstract

Abstract Krishnamurthy Konduru and Gerardo Kaplan Laboratory of Emerging Pathogens, Division ofEmerging and Transfusion Transmitted Diseases, Center for Biologics Evaluationand Research, Food and Drug Administration, Silver Spring, MD 20993. Recent Ebola virus(EBOV) epidemic in West Africa underscores the urgent need of vaccines ortherapeutics. Here we describe the development of EBOV and Marburg virus (MARV) subunit vaccines based on the extracellular domain of the viral glycoprotein (GP) fused to the Fc fragment of human IgG (EBOV gp-Fc or MARV gp-Fc) and expressed in mammalian cells. These GP fusion proteins undergo the complex post-translational processing observed in the membrane-bound GP. In vaccinated mice, EBOV gp-Fc induced high levels of total and neutralizing anti-GP antibodies and elicited T-cell immunity characterized by the production of IFNγ (Konduru et al. 2011). Vaccinated guinea pigs developed a strong humoral response as measured by total and neutralizing antibodies to GP, and were completely protected against EBOV lethal challenge (Konduru et al. 2016). We are currently extending our studies to the filo virus lethal challenge model in monkeys. Our preliminary data indicates that EBOV gp-Fc and MARV gp-Fc induces total and neutralizing antibodies as well as recall CD8+ T-cell immunity as assessed by the production of IFNγ and TNFα in PBMC. Further experiments, including protection against lethal challenge in monkeys, will be required to determine whether Filovirus GP-Fc fusion proteins could be developed as a candidate vaccine.