A Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls

Summary

Cervical cancer is the most common cancer in women aged 15-44 years in East Africa, and mortality rates are very high. HPV vaccines are most effective if given to girls who have not yet acquired HPV infection. In Tanzania, HPV vaccine has been shown to be safe, acceptable and can be delivered with high coverage (\~80%). However, the cost of delivering HPV vaccine is considerably higher than costs for traditional infant/child vaccinations. This is primarily because of costs to establish outreach programmes and associated personnel costs including nurses who must spend significant time away from their posts to deliver vaccine, especially if multiple doses are needed. There is global interest in simplifying HPV vaccine delivery by reducing the number of doses. If a single dose could be given, this could halve the costs of delivery, making it more accessible to the populations that need it most. Recently, the WHO recommended that 2 doses of HPV vaccine could be given to young girls, based on studies in high and upper middle-income countries. However in Africa high rates of infections like malaria and worms can affect immune responses to vaccines. It is essential to know that reducing the number of doses does not reduce the protective immune response of these vaccines. The investigators are conducting a trial in Tanzanian girls 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. Two different HPV vaccines, the bivalent (2-v) vaccine that protects against HPV 16/18 (the cause of 70% of cancers) and the 9-valent (9-v) vaccine that protects against 9 HPV types, will be compared. The trial will randomise 900 girls to 6 arms and follow them for 36 months. Girls will receive the 2-v or the 9-v HPV vaccine, as 1, 2 or 3 doses. Girls receiving 1 or 2 doses will be compared 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 3 doses. Girls in the 1 and 2 dose arms will be enrolled in an extension and followed for up to 9 years, to examine the stability of immune responses. The immune responses in this study will also be compared with results from other countries where the vaccine has been shown to be protective. This will provide information about whether a reduced number of doses is likely to be protective in Africa. This work will be extremely important in informing future HPV vaccination strategies and will be one of the first randomised trials of 1 and 2 doses of any HPV vaccine in Africa.

Timeline

Start

2017-02-23

Primary completion

2020-01-15

Completion

2027-03

Publications

• Results Baisley K, Kemp TJ, Kreimer AR, Basu P, Changalucha J, Hildesheim A, Porras C, Whitworth H, Herrero R, Lacey CJ, Schiller JT, Lucas E, Mutani P, Dillner J, Indangasi J, Muwonge R, Hayes RJ, Pinto LA, Watson-Jones D. Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose of HPV vaccine in historical cohorts: an immunobridging analysis of a randomised controlled trial. Lancet Glob Health. 2022 Oct;10(10):e1485-e1493. doi: 10.1016/S2214-109X(22)00306-0.
• Results Baisley KJ, Whitworth HS, Changalucha J, Pinto L, Dillner J, Kapiga S, de Sanjose S, Mayaud P, Hayes RJ, Lacey CJ, Watson-Jones D. A dose-reduction HPV vaccine immunobridging trial of two HPV vaccines among adolescent girls in Tanzania (the DoRIS trial) - Study protocol for a randomised controlled trial. Contemp Clin Trials. 2021 Feb;101:106266. doi: 10.1016/j.cct.2021.106266. Epub 2021 Jan 6.
• Results Watson-Jones D, Changalucha J, Whitworth H, Pinto L, Mutani P, Indangasi J, Kemp T, Hashim R, Kamala B, Wiggins R, Songoro T, Connor N, Mbwanji G, Pavon MA, Lowe B, Mmbando D, Kapiga S, Mayaud P, de SanJose S, Dillner J, Hayes RJ, Lacey CJ, Baisley K. Immunogenicity and safety of one-dose human papillomavirus vaccine compared with two or three doses in Tanzanian girls (DoRIS): an open-label, randomised, non-inferiority trial. Lancet Glob Health. 2022 Oct;10(10):e1473-e1484. doi: 10.1016/S2214-109X(22)00309-6.
• Results Watson-Jones D, Changalucha J, Maxwell C, Whitworth H, Mutani P, Kemp TJ, Kamala B, Indangasi J, Constantine G, Hashim R, Mwanzalima D, Wiggins R, Mmbando D, Connor N, Pavon MA, Lowe B, Kapiga S, Mayaud P, de Sanjose S, Dillner J, Hayes RJ, Lacey CJ, Pinto L, Baisley K. Durability of immunogenicity at 5 years after a single dose of human papillomavirus vaccine compared with two doses in Tanzanian girls aged 9-14 years: results of the long-term extension of the DoRIS randomised trial. Lancet Glob Health. 2025 Feb;13(2):e319-e328. doi: 10.1016/S2214-109X(24)00477-7.
• Results Baisley K, Kemp TJ, Mugo NR, Whitworth H, Onono MA, Njoroge B, Indangasi J, Bukusi EA, Prabhu PR, Mutani P, Galloway DA, Mwanzalime D, Kapiga S, Lacey CJ, Hayes RJ, Changalucha J, Pinto LA, Barnabas RV, Watson-Jones D. Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose in young women aged 15-20 years in Kenya (KEN SHE): an immunobridging analysis of randomised controlled trials. Lancet Glob Health. 2024 Mar;12(3):e491-e499. doi: 10.1016/S2214-109X(23)00586-7.
• Whitworth HS, Beshir KB, Baisley KJ, Mbwanji G, Indangasi J, Kemp T, Kamala B, Maxwell C, Hashim R, Mukerebe C, Mayaud P, Lowe B, Gabriel N, Connor N, Kapiga S, De Sanjose S, Lacey CJ, Hayes RJ, Pinto L, Changalucha J, Sutherland CJ, Watson-Jones D. Effect of malaria parasitaemia on antibody responses to single-dose and two-dose HPV vaccination: results from the DoRIS dose-reduction immunogenicity trial in Tanzanian girls. Vaccine. 2026 Jun 30;89:128889. doi: 10.1016/j.vaccine.2026.128889. Online ahead of print.
• Kemp TJ, Baisley K, Changalucha J, Indangasi J, Whitworth H, Lacey CJ, Mwanzalima D, Hashim R, Kapiga S, Hayes RJ, Pinto LA, Watson-Jones D. Immunogenicity of one and two doses of Gardasil(R)9 in Tanzanian girls in the DoRIS Trial. NPJ Vaccines. 2025 Dec 19;11(1):22. doi: 10.1038/s41541-025-01344-1.
• Hsiao A, Struckmann V, Stephani V, Mmbando D, Changalucha J, Baisley K, Levin A, Morgan W, Hutubessy R, Watson-Jones D, Whitworth H, Quentin W. Costs of delivering human papillomavirus vaccination using a one- or two-dose strategy in Tanzania. Vaccine. 2023 Jan 9;41(2):372-379. doi: 10.1016/j.vaccine.2022.11.032. Epub 2022 Nov 29.

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