Murine cytomegalovirus: A potent antigen delivery vector

South Dakota State University, Brookings SD

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Cytomegaloviruses (CMVs) are highly species-specific. Thus, murine CMV (MCMV) is often used as a model system to study human CMV (HCMV) infection due to the significant similarities of the two viruses in their biological, genetic and pathogenic properties. We have recently shown that MCMV undergoes abortive infection in human dendritic cells (DC), but efficiently transduces foreign genes into human DC, leading to DC maturation and activation of normal immunostimulatory activity. Additionally, we showed that human DC infected with MCMV-vectored human immunodeficiency virus-1 (HIV-1) gp120 was capable of stimulating the expansion of gp120-specific T cells from autologous naive PBMC in vitro. This strongly supports the potential use of MCMV as an antigen delivery vehicle for vaccine development. In this proposed study, we aim to further explore the central hypothesis that MCMV is a potent vaccine delivery vehicle due to its ability to efficiently infect antigen-presenting cells including DC and monocytes/macrophages, without down-regulating their immunostimulatory activity. We will examine this hypothesis by performing experiments to (i) Examine in greater detail the nature of abortive infection, which MCMV undergoes in human DC, and determine the mechanistic basis of human DC activation by MCMV; (ii) Determine the cytokine profile of MCMV-transduced human DC and assess the specificity of MCMV-gp120 infected DC in stimulating potent antigen-specific T cell expansion from autologous naive PBMC; (iii) Examine the nature of infection, which MCMV undergoes in human monocytes/macrophages and the immunomodulatory function of MCMV on human monocytes/macrophages. Overall, these proposed experiments are expected to provide more information regarding the potential utility of MCMV as a potent antigen delivery vector.