HPV Vaccination in Africa- New Delivery Schedules Alias The HANDS HPV Vaccine Trial

Human Papillomavirus Vaccine

HPV vaccination in healthy females

A randomized, observer-blind non-inferiority trial to evaluate alternative human papillomavirus (HPV) vaccination schedules in young females in West Africa.

This study is a randomized, open-label, single-centre, phase 3 non-inferiority clinical trial of the Gardasil 9 vaccine. It will be undertaken in three female cohorts (15 to 26 years old; 9 to 14 years-olds and 4 to 8 year-olds). In total 1720 female participants will be recruited in a rural setting in The Gambia, West Africa. The Gardasil 9 vaccine is a recombinant L 1 VLP vaccine containing HPV types 6, 11,16,18,31,33,45,52 and 58 VLP. It is licensed by both European Medicines Agency and the US Food and Drug Administration as a two or three dose schedule to 9 to 14 year olds and as a three dose schedule to 15 to 26 years olds. The license covers both males and females. The vaccine is not currently licensed for those under 9 years of age and it is not licenced in The Gambia. All females within the 15 to 26 year-old cohort will receive three doses of Gardasil 9 at 0, 2 and 6 months and represent the reference group for the purposes of the serological non-inferiority analysis. This is the only group for which efficacy data for the vaccine are available. Females in the 9 to 14 year old and 4 to 8 year old cohorts will be randomized to receive either one or two doses of Gardasil 9. In both groups, the two doses will be administered at 0 and 6 months. The primary and secondary immunogenicity objectives will be analysed based on serological Samples taken 4 to 6 weeks after the last dose of vaccine received according to group. Additional analysis will be undertaken at 12, 24 and 36 months. The Sampling schedule is aligned with the schedule in other immunogenicity trials to facilitate comparison and potential immunobridging to future one-dose efficacy data. In addition, the stability of the antibody concentrations between 12 and 24 and again between 24 and 36 months according to schedule and age-group aims to allow longer term predictions regarding the maintenance of antibody concentration to be made. A Sub-study will be undertaken within the main trial to compare in detail early immunological events taking place following Gardasil 9. The quantitative and qualitative changes in these events following a first and following subsequent doses of the vaccine and also according to age will be assessed and related to the early and long-term antibody concentrations induced by the vaccine. There are currently no data exploring the basis for the progressive increase in the immunogenicity of the HPV vaccines apparent with decreasing age. These may have their origins in the early innate response following vaccination-which will be assessed at a cellular as well as transcriptomic level, as well as in the subsequent adaptive profile. Similarly, the cellular basis for the sustained seropositivity induced by the HPV vaccines even apparent following a single vaccine dose is little understood. The window onto which plasmablasts and memory B-cell populations in the circulation is transient following vaccination. However, enumerating and characterizing these populations and relating them in the same way to early and long term antibody concentration aims to provide insight into the relative roles of these populations and how they are influenced by the age of the vaccine and the number of vaccine doses received. Individuals in the sub-study will contribute serological data to the main trial and will be followed up in the same way but will be consented for one additional blood sample after each vaccination. Up to 120 participant in each group in the main trial will be randomized to groups A, B or C, with 40 participants in each of these groups. This number aims to generate a dataset of at least 30 analyzable individuals per schedule and age group.

The Gambia