Evaluation of Long-term Immunological Responses Following Reduced Dose Quadrivalent Human Papillomavirus (HPV) Vaccine Schedules: A Phase II/III Clinical Trial

In 2008/9, the Ministry of Health (MoH) in Fiji accepted a donation of 110,000 doses of quadrivalent HPV vaccine, Gardasil® based on the high cervical cancer disease burden. There was enough vaccine to vaccinate all girls aged 9-12 years (30,338 girls) with a three-dose schedule, but not all girls received three doses of the vaccine. This means those girls that received reduced doses may not be fully protected against the HPV genotypes present in the Gardasil®. In 2013, the Fiji MoH with Australian Aid support introduced the Cervarix ® vaccine as a three dose schedule (0, 1, and 6 months) to be given to all girls at the last year of primary school as part of the national immunisation program. This is a unique opportunity to determine if fewer than three doses of Gardasil® vaccine are immunologically similar to the standard three-dose schedule 6 years after receiving the vaccine (ie indicating long-term protection).

This is an open label Phase II/III clinical trial in girls (now aged 14-17 years) who previously received zero, one, two or three doses of Gardasil® in 2008/9. A dose of Cervarix ® will be administered to all the girls in this study so that immunological evidence of long-term protection in terms of antibody levels (including neutralisation titres), number of memory B and T cells (including cytokine responses) and gene expression profiles can be measured.

A non-random sample of 200 girls will be recruited; girls previously received one, two or three doses of Gardasil® will be identified through school vaccination lists obtained from the MoH and Ministry of Education; girls that did not receive any vaccines previously will be recruited via recommendations of friends of the girls and by informal networks. The investigators aim to have approximately 50% indigenous Fijian (i-Taukei)/others and 50% Fijians of Indian descent in the study.

Informed consents will be obtained from both the parent/guardian of the participant and the participant, as well as checking the participant's eligibility by the study nurses. Twenty-five milliliters (mL) of blood in total will be drawn from each participant before and 28 days after a dose of Cervarix® vaccine. To ensure all participants receive three doses of HPV vaccine by the end of study, follow up appointments will be made for study participants to receive off-study vaccine for those that did not receive any HPV vaccine previously or received only one dose of Gardasil® in 2008/9 campaign; no samples will be collected in the follow-up appointments.

Peripheral blood mononuclear cells (PBMC) and plasma will be separated from the blood, and freeze down down in liquid nitrogen and -80 degree freezer until laboratory analysis, respectively.