Papillomavirus-like particle based vaccines: cervical cancer and beyond

Non-infectious human papillomavirus-like particles (VLP), composed of the L l major capsid protein, are under active development as vaccines to prevent cervical cancer. They would presumably function primarily by generating vi rion-neutralising antibodies against the genital human papillomavirus (HPV) types that are the principal cause of most cervical cancers. Early phase c linical studies indicate that the VLP vaccines are well tolerated and able to consistently induce high titres of virus type-specific neutralising anti bodies. Two types of second-generation VLP-based subunit vaccines with ther apeutic implications, both related and unrelated to papillomavirus infectio n, are in preclinical development. One type seeks to induce cell-mediated i mmune responses, especially cytotoxic lymphocytes (CTL) against non-structu ral papillomavirus proteins, proteins of other viruses, or tumour associate d antigens. The target antigen is incorporated into the VLPs as a fusion pr otein of L1 or the L2 minor capsid protein. In mouse models, this approach has generated potent CTL responses after low dose vaccination in the absenc e adjuvant. The second type of therapeutic VLP-based vaccine seeks to gener ate autoantibodies to self-antigens. The display of self polypeptides in th e context of the highly ordered array of repetitive elements on the papillo mavirus VLP surface abrogates the ability of the humoral immune system to f unctionally distinguish between foreign and self. High titre and high avidi ty auto-reactive IgG antibodies have been induced to both soluble (TNF-alph a) and cell surface (CCR5) central self-antigens. Vaccines based on this ap proach could potentially be effective alternatives to monoclonal antibody ( mAb)-based therapies for a variety of disease targets.