ABSTRACT

To vaccinate against a viral infection or to conduct gene or immune therapy, many transfer systems based on viruses as vectors have been explored [1]. Earlier, some such vectors have had the disadvantage of maintaining viral genes that could potentially interfere with host genes or be abrogated by preexisting immunity to the virus [1]. This leads to the search for new vectors, and today, there are a plethora of different types of vectors of which some are based on virus-like particles (VLPs) [2,3]. Here, the focus is directed only on those based on polyomaviruses (PyVs) and human papillomaviruses (HPVs), which lack viral genes and are nonreplicative and nonpathogenic and where the former have been used for vaccination with very little side effects [2-8]. The fact that the capsids of these VLPs are easy to modify

and that they can be produced industrially for vaccine use has increased the awareness of the potential use of VLPs as vaccines, as well as vectors for immune therapy of cancer patients or patients with other diseases or conditions [2-8]. PyV and HPV VLPs consist of one or more viral structural proteins that can be produced in, for example, yeast cells, insect cells using baculoviruses, Escherichia coli, tobacco chloroplasts, or mammalian cells and spontaneously assemble into VLPs similar to the equivalent virions, but lacking viral genes [9-12]. Industrial production, as mentioned earlier, using yeast and baculovirus, respectively, has been used for the manufacturing of the two HPV vaccines Gardasil and Cervarix [5]. PyV and HPV VLPs can induce antibody responses against the corresponding virions and bind to cellular receptors, similar to that of the equivalent

19.1 Introduction .................................................................................................................................................................... 295 19.2 PyVs and PyV-Based VLPs ........................................................................................................................................... 296

19.2.1 HPyVs................................................................................................................................................................. 296 19.3 HPV and HPV-Based VLPs ........................................................................................................................................... 297 19.4 HPV and HPyV VLPs as Preventive Vaccines .............................................................................................................. 297

19.4.1 HPV VLPs as Vaccines against Viral Infection ................................................................................................ 297 19.4.2 PyV VLPs as Vaccines against Viral Infection in Normal and T-Cell Dysfunctional

Mice and for Potential Use in Humans .............................................................................................................. 298 19.5 Chimeric VLPs for Vaccination against Virus-Induced Tumors ................................................................................... 298

19.5.1 Chimeric VLPs .................................................................................................................................................. 298 19.5.2 Chimeric HPV VLPs for Vaccination against HPV-Induced Tumors ............................................................... 298 19.5.3 MPyV VLPs as Vaccine against Induced MPyV Tumors ................................................................................. 298

19.6 PyV Chimeric VLPs for Preventive and Therapeutic Immune Therapy of Nonviral Cancer ....................................... 299 19.7 Loading of Dendritic Cells with PyV VLPs and HPV VLPs and Use of Adjuvant ...................................................... 299 19.8 PyV VLPs as Vectors for Gene Therapy and to Augment DNA Immunization ........................................................... 299 19.9 Mutated HPV VLPs as Vectors for Gene Therapy ........................................................................................................ 300 19.10 Conclusion ...................................................................................................................................................................... 300 Acknowledgments ..................................................................................................................................................................... 300 References ................................................................................................................................................................................. 300

virions  [2,3]. Nonspecies-specic VLPs can also be used to introduce DNA or proteins into cells in  vivo, this way avoiding the disadvantage of preexisting antibodies that may abrogate the efcacy of the vectors [2-8,13-18]. However, recently, many more HPVs and human PyVs (HPyVs) have been discovered, potentially offering a broader spectrum of VLP choices [3]. In the following, some aspects of the use of PyV-and HPV-based VLPs as vaccines but also as vectors for immune therapy and gene therapy are presented.