Immune response to the Human Papillomavirus
Immune response to HPV in primary infection
Human papillomavirus infection of the cervix is relatively common in young sexually active women .The majority of infections are transient and not clinically evident with 70-90% of infections clearing within 12-30 months. This suggests that host immunity is generally able to clear HPV infection. The fact that HPV remains localised to cervix and vagina further indicates that local immune responses are sufficient in controlling and resolving HPV infection. Both cell mediated immunity and humoral immunity (Antibody responses) have been implicated in the susceptibility, persistence and clearance of genital HPV infection.
Although HPV infection is known to generate an immune response, it is an elusive target for the immune system and the immune responses are generally weak. Several mechanisms are involved which contribute to immune evasion.
1) HPV is non cytopathic i.e. The viruses do not lyse cells unlike the herpes viruses for example. They cause cell proliferation rather than cell destruction and as such do not invoke an inflammatory response
2) The fact that HPV only infects epithelial cells facilitates evasion of the immune system. Complete HPV virions are only found in terminally differentiating squamous cells in the outer layers of the genital epithelium, separated by several layers of mucosal epithelium from the lymphocytic germinal centres in the submucosa which are involved in generating the immune response
3) HPV avoids recognition of the innate immune system by blocking the production of interferons to ensure its own replication. This is achieved by the production of two early proteins E6 and E7 that bind to and inactivate intermediates in the interferon cascade.
Knowledge about the immune response to HPV is important for the production of appropriate vaccines against the viruses. An ideal HPV vaccine should induce both antibody and cellular immunity. Studies have shown that the major capsid protein L1 is essential in this respect. In canine and rabbit models of HPV infection immunisation with papillomavirus L1 virus like particles (VLPs) induces neutralising antibodies and totally protects immunised animals from challenge. There have been two successful clinical trials using vaccines prepared from VLPs the results of which are discussed in the next section.
Strategies for the production of other HPV vaccines using different production systems can be found in the following publication:
Strategies for the prevention of cervical cancer by human papillomavirus vaccination by A-L Williamson Williamson . J.-A Passmore and E.P.Rybicki in Best Practice and Research in Clinical Obstetrics and Gynaecology2005 vol 19, no4, pp 531 – 544 Also available on line at www.sciencedirect.com).