Human Papilloma Virus
Background
Human papillomaviruses (HPV) are responsible for virtually all cases of cervical cancer and a significant proportion of other anogenital and oropharyngeal cancers. Half a million cases of cervical cancer occur each year in low and middle income countries, largely due to the lack of cytological screening programmes. Licensed HPV vaccines are highly effective in preventing incident infection and consequent pre-malignant disease and could substantially reduce cervical cancers in resource-poor setting if widely implemented. However, such impact may not be evident for 20-30 years, which leaves a gap in coverage for the millions of women already persistently infected with high-risk (HR) HPV. In addition, there is a lack of effective screening for other HPV-driven anogenital cancers.
HPV is an attractive target for immunotherapeutic approaches to induce or enhance cell-mediated immunity since this is key to the elimination of persistent infection and also spontaneous regression of dysplasia. However, therapeutic vaccine strategies tested in clinical trials to date have had modest potency and have focused on only one or two high-risk (HR) genotypes.
Pre-clinical vaccine development and early clinical studies
We are developing new vaccines that exploit potent replication-defective simian adenovirus and poxvirus vectors to deliver novel immunogens representing multiple HR genotypes. A unique feature of the immunogen design is the selection of conserved viral sequences; our goal is to achieve broad coverage of HR genotypes, while also accurately reflecting their global representation. These vaccine candidates will be tested for immunogenicity and efficacy in mouse models; the most promising regimens will be advanced to phase I clinical trials. In parallel, we will complement this work with human studies to characterise cell-mediated immune responses to the major HR HPV genotypes in women with current or past infection, in order to ensure that critical viral targets are included in our vaccine candidates.
