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S12.1 Human Papillomavirus Vaccines - Correlates of Protection Are Not Defined
  1. A Williamson
  1. University of Cape Town, Cape Town, South Africa

Abstract

Specific types of human papillomavirus (HPV) are causally associated with cervical cancer, with at least 99% of cervical cancers having detectable HPV DNA. Other cancers that also have an association with HPV include anogenital and oropharyngeal malignancies affecting both males and females. Over two thirds of these cancers are associated with HPV types 16 and 18, which are the high-risk types targeted by the HPV vaccines Gardasil and Cervarix. Gardasil also protects from infection with HPV-6 and HPV-11, which cause genital warts and recurrent respiratory papillomatosis. The vaccines are based on the major capsid protein, L1, which self assembles into virus-like particles. Although HPV L1 is a relatively conserved gene with different HPV types having L1 sequence homology of up to 90%, the vaccine induced protection is HPV type-specific. Both vaccines induce excellent protection against the specific types targeted; however, there is also limited protection from infection with closely related HPV types. The vaccines do not cause regression of established genital lesions: regression is due to cell-mediated immunity. The serological correlates of protection of the vaccines are not defined but it is likely that protection is largely due to neutralising antibodies: animal studies have shown that protection can be transferred by passive immunisation with immune sera. In natural infections, titres of HPV antibodies are much lower than for vaccine induced antibodies, and in fact not all infected people develop detectable antibodies. It is likely that serological correlates of protection will become better defined only if vaccine induced protection starts to wane as the antibody titres potentially drop over time; it may then be possible to define levels of antibody needed for protection. Such information could inform the need for further booster vaccinations.

  • papillomavirus

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