Abstract

The ability to generate human papillomavirus (HPV) virus like particles (VLPs) by the synthesis and self-assembly in vitro of the major virus capsid protein L1 has transformed our prospects for preventing cervical carcinoma in women. Immunisation with L1 VL Ps provides type specific protection in all the animal infections so far tested. In Phase I trials in humans HPV L1 VLP vaccines are safe and highly immunogenic stimulating robust B and T cell responses and generating high titres of neutralising antibody. In the Phase II and III trial antibody levels persist at measurable levels for at least 48 months post vaccination suggesting that strong immune memory is generated. At present the assumption is that the protection achieved by these vaccines against incident HPV infection and HPV associated ano-genital pathology is mediated via serum neutralising IgG. However, since there have been no vaccine failures thus far, immune correlates of protection have not been established. The available evidence is that the immunodominant neutralising antibodies generated in natural infections are type-specific and are not cross-neutralising although highly homologous HPV pairs share minor cross- neutralisation epitopes. Cross reactive and cross neutralising antibodies are generated in HPV L1 vaccinees but at significantly lower titres and the duration of any cross protection that might be elicited is uncertain. L1 VLP vaccines are prophylactic not therapeutic vaccines and for maximal population effectiveness should be delivered before the sexual debut to pre-pubertal females (or males) and social and cultural issues may be important in determining vaccine takeup.