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Prophylactic HPV Vaccines
  1. Margaret Stanley (mas{at}mole.bio.cam.ac.uk)
  1. University of Cambridge, United Kingdom

    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 both benign and malignant HPV associated genital disease and in particular for reducing significantly the incidence of cervical carcinoma in women. Two HPV L1 VLP vaccines have been developed, both have been shown to be safe and highly immunogenic generating high titres of neutralising antibody that persist at measurable levels higher than those measured in natural infections for at least 60 months post vaccination suggesting that strong immune memory is generated At present the assumption is that the protection achieved by these vaccines against HPV induced 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 cross-neutralisation epitopes. Cross reactive and cross neutralising antibodies are generated in HPV L1 vaccinees but at lower concentrations, cross protect ion against incident infection has been shown but 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 robust antibody responses have been demonstrated in immunogenicity bridging studies in 9-15 year old boys and girls. However social and cultural issues may be important in determining vaccine take up in the optimal cohort.

    • Cervical carcinoma
    • HPV
    • antibody immune responses
    • virus like particles

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