Development of prophylactic HPV vaccines.
Since several years it has been accepted that persistent infection with certain (so called-high risk: HR) types of Human papillomaviruses (HPV) represents a strong risk factor for cervical cancer. The most frequent HR HPV types 16 and 18 account for about 70% of this tumour, which is the second most frequent malignancy in women worldwide. Several studies in animal papillomavirus models revealed that protection against infection is conferred by neutralizing antibodies directed against conformational epitopes of the major structural protein L1. Such antibodies can most efficiently be induced by immunization with virus-like particles (VLP) that assemble spontaneously following expression of L1 in recombinant vectors. Large-scale production of HPV 16 and 18 VLPs proved to be successful facilitating, a few years ago, first clinical trials on safety and immunogenicity. In the meantime more than 25,000 women have been included into several efficacy trials which demonstrated protection against persistent infection with HPV 16 and 18 and against the development of precursor lesions to cervical cancer. Although the ultimate proof of success, i.e. reduction of cancer incidence still requires the immunization of large populations and many years of follow-up, the existing data are so persuasive that the responsible agencies in several countries permitted the licensing of the first HPV vaccine in 2006. Several questions such as the duration of protection, the need development of for post-exposure vaccination strategies and availability of such vaccine in low-budget countries are open and will be discussed.
Gissmann
Lutz
L
Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany. l.gissmann@dkfz.de
Müller
Martin
M
D000818:Animals; D000914:Antibodies, Viral / Q000187:drug effects*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000517:prevention & control* / Q000821:virology
D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines