Papillomavirus-like particle based vaccines: cervical cancer and beyond

Abstract

Non-infectious human papillomavirus-like particles (VLP), composed of the L1 major capsid protein, are under active development as vaccines to prevent cervical cancer. They would presumably function primarily by generating virion-neutralising antibodies against the genital human papillomavirus (HPV) types that are the principal cause of most cervical cancers. Early phase clinical studies indicate that the VLP vaccines are well tolerated and able to consistently induce high titres of virus type-specific neutralising antibodies. Two types of second-generation VLP-based subunit vaccines with therapeutic implications, both related and unrelated to papillomavirus infection, are in preclinical development. One type seeks to induce cell-mediated immune responses, especially cytotoxic lymphocytes (CTL), against non-structural papillomavirus proteins, proteins of other viruses, or tumour associated antigens. The target antigen is incorporated into the VLPs as a fusion protein of L1 or the L2 minor capsid protein. In mouse models, this approach has generated potent CTL responses after low dose vaccination in the absence adjuvant. The second type of therapeutic VLP-based vaccine seeks to generate autoantibodies to self-antigens. The display of self polypeptides in the context of the highly ordered array of repetitive elements on the papillomavirus VLP surface abrogates the ability of the humoral immune system to functionally distinguish between foreign and self. High titre and high avidity auto-reactive IgG antibodies have been induced to both soluble (TNF-alpha) and cell surface (CCR5) central self-antigens. Vaccines based on this approach could potentially be effective alternatives to monoclonal antibody (mAb)-based therapies for a variety of disease targets.