Murine Polyomavirus Virus-like Particles (VLPs) as Vectors for Gene and Immune Therapy and Vaccines against Viral Infections and Cancer

Abstract

This review describes the use of murine polyomavirus “virus-like” particles (MPyV-VLPs), free from viral genes, as vectors for gene and immune therapy and as vaccines. For large-scale MPyV-VLP manufacture, VP1 is produced in a baculovirus insect cell system, E. coli or in yeast. MPyV-VLPs bind eukaryotic DNA and introduce this DNA into various cell types in vitro and in vivo. In normal and T-cell-deficient mice, this results in the production of anti-MPyV-VLP (and MPyV) antibodies. Furthermore, repeated MPyV-VLP vaccination has been shown to prevent primary MPyV infection in normal and T-cell-deficient mice, and the outgrowth of some MPyV-induced tumours in normal mice. Moreover, when inoculated with gene constructs encoding for HIV p24, MPyV-VLPs augment the antibody response to p24. In addition, MPyV-VLPs, containing fusion proteins between the VP2 or VP3 capsid protein and selected antigens, can be used as vaccines. Notably, one vaccination with MPyV-VLPs, containing a fusion protein between VP2 and the extracellular and transmembrane parts of the HER-2/neu oncogene, immunizes against outgrowth of a HER-2/neu-expressing tumour in Balb/c mice and also against the development of mammary carcinomas in BALB-neuT transgenic mice. Finally, a second polyoma VLP-vector based on murine pneumotropic virus (MPtV-VLP), which does not cross-react serologically with MPyV-VLP (and MPyV), has been developed and can be used to conduct prime boost gene and immune therapy and vaccination. In summary, MPyV-VLPs are useful vectors for gene therapy, immune therapy and as vaccines and, in combination with MPyV-VLPs, MPtV-VLPs are potentially useful as prime-boost vectors.