A Dose Reduction Immunobridging Study of two HPV vaccines in Tanzanian girls Cervical cancer is the commonest cancer among women aged between 15 and 44 years in Tanzania. Mortality from the disease is extremely high because screening programmes are frequently absent or limited in scale and women usually present late, leaving palliative care as the only option. HPV vaccines are most effective if provided to girls who have not yet acquired HPV infection. In Tanzania we have shown that HPV vaccine is safe, is very acceptable and can be delivered with high coverage (around 80%) but setting up and sustaining an HPV vaccination programme for young girls requires considerable investment in human and financial resources.     Despite high acceptability of the vaccine in East Africa, a number of studies have estimated that the cost of delivering HPV vaccine is considerably higher than costs for delivering traditional infant/child vaccinations, even if vaccine is subsidized by the GAVI Alliance. This is primarily because of start-up costs to establish outreach programmes and associated personnel costs with involvement of teachers and nurses who must spend significant time away from their health posts to deliver vaccine, especially if multiple doses are needed.    There is global interest in simplifying delivery by reducing the number of doses of HPV vaccine. The cost savings of offering fewer doses of HPV vaccine would be substantial and would also result in less time that health personnel are away from their stations and simplification of vaccine delivery. If a single dose could be given, this could halve the costs of vaccine delivery, making HPV vaccine more accessible to the populations that need it most. Recently, the WHO recommended that 2 doses of HPV vaccine could be given to girls aged less than15 years, based on studies in high and upper middle income countries. However in Africa there are high rates of infections like malaria and worms that can affect immune responses to vaccines. We need be sure that a reduction in the number of vaccine doses does not reduce the protective immune response of these vaccines.    We are planning a randomised trial in healthy Tanzanian females aged 9-14 years to establish whether a single dose of HPV vaccine produces immune responses that are likely to be effective in preventing cervical cancer in Africa. We will compare two different HPV vaccines, the bivalent (2-v) vaccine that protects against HPV 16/18 (the cause of 70% of cancers) and a new 9-valent (9-v) vaccine that protects against 9 HPV types.    Our trial will enrol and randomise 900 girls aged 9-14 years into 6 groups. They will receive either the 2-v or the 9-v HPV vaccine, as 1, 2 or 3 doses. Girls will be followed up for 36 months after the first dose so we can measure the quality and sustainability of immune responses. We will compare the girls receiving 1 or 2 doses with those receiving 3 doses of the same vaccine, to ensure that the reduced dose regimen produces an immune response that is not inferior to the standard 3 doses. We will also compare the immune responses in our study with results from other countries without a high prevalence of malaria and worm infections, and where the vaccine has been shown to be protective. This will give us information about whether a reduction in the number of doses is likely to be protective in Africa.      This trial will address fundamental questions about HPV vaccine dose reduction in a setting where the potential impact is greatest, and will be extremely important in informing future HPV vaccination policy. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.