A prophylactic human papilloma vaccine (Gardasil) [targeting virus types 6,11,16,18] has recently been introduced in Ireland. In 2007, it is anticipated that a second human papilloma virus vaccine (Cervarix) [targeting virus types 16,18] will be introduced. This project will examine the effect of introducing a human papilloma virus vaccine in the Irish population, the influence of HLA haplotype immune regulating genes on vaccine efficacy and through a proteome approach will attempt to stratify vaccine responses in vaccinated women.
Women will be enrolled in the study from a college based student population, with the enrolment point as the student health screen visit. Women will have a cervical human papilloma virus test smear/swab at the start of the study. In addition, the effect of vaccinating men against high risk human papilloma virus will also be evaluated.
HLA haplotyping will be performed on all vaccinated women using HLA sequencing based typing. The systemic immune response to vaccination will be examined using peripheral blood from vaccinated patients, before and after 'vaccination events'. A time course study at time 0, 1 month post-vaccination, year 1, 2 and 3 post-vaccination will be examined. The specific cytokine immune response will be examined using low density cytokine arrays (LDAs) at 1 month and 1 year post-vaccination. Using an antibody-array proteomic approach, a protein signature profile for vaccine responders will be established for vaccinated women correlated with HLA haplotype for the selected loci. All women will have a human papilloma virus DNA test at yr 1, 2 and 3 post-vaccination.
The systemic immune, antigen-specific cellular, cytokine and antibody responses to human papilloma virus LI VLPs in a time course study post vaccination will be examined. We will assess the longitudinal risk of developing human papilloma virus-associated high grade CIN/cGIN and invasive cervical cancer in the context of vaccination over a 4-5 year period and the effect of HLA haplotype on vaccine efficiency. A protein signature profile for vaccine responders will be developed.
The following specific scientific outputs are expected by the ICSRC in project 7:
