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.

Autor:	Watson-Jones D; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: deborah.watson-jones@lshtm.ac.uk., Changalucha J; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania., Whitworth H; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK., Pinto L; HPV Serology Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA., Mutani P; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania., Indangasi J; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK., Kemp T; HPV Serology Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA., Hashim R; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania., Kamala B; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania., Wiggins R; York Biomedical Research Institute & Hull York Medical School, University of York, York, UK., Songoro T; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania., Connor N; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK., Mbwanji G; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania., Pavon MA; Infection and Cancer Laboratory, Cancer Epidemiology Research Programme, ICO-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain., Lowe B; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK., Mmbando D; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania., Kapiga S; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK., Mayaud P; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK., de SanJosé S; Unit of Infections and Cancer Cancer Epidemiology Research Programme, Institut Català d' Oncologia, Barcelona, Spain; National Cancer Institute, Rockville, USA., Dillner J; Karolinska Institute, Stockholm, Sweden., Hayes RJ; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK., Lacey CJ; York Biomedical Research Institute & Hull York Medical School, University of York, York, UK., Baisley K; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
Jazyk:	angličtina
Zdroj:	The Lancet. Global health [Lancet Glob Health] 2022 Oct; Vol. 10 (10), pp. e1473-e1484.
DOI:	10.1016/S2214-109X(22)00309-6
Abstrakt:	Background: An estimated 15% of girls aged 9-14 years worldwide have been vaccinated against human papillomavirus (HPV) with the recommended two-dose or three-dose schedules. A one-dose HPV vaccine schedule would be simpler and cheaper to deliver. We report immunogenicity and safety results of different doses of two different HPV vaccines in Tanzanian girls. Methods: In this open-label, randomised, phase 3, non-inferiority trial, we enrolled healthy schoolgirls aged 9-14 years from Government schools in Mwanza, Tanzania. Eligible participants were randomly assigned to receive one, two, or three doses of either the 2-valent vaccine (Cervarix, GSK Biologicals, Rixensart) or the 9-valent vaccine (Gardasil-9, Sanofi Pasteur MSD, Lyon). The primary outcome was HPV 16 specific or HPV 18 specific seropositivity following one dose compared with two or three doses of the same HPV vaccine 24 months after vaccination. Safety was assessed as solicited adverse events up to 30 days after each dose and unsolicited adverse events up to 24 months after vaccination or to last study visit. The primary outcome was done in the per-protocol population, and safety was analysed in the total vaccinated population. This study was registered in ClinicalTrials.gov, NCT02834637. Findings: Between Feb 23, 2017, and Jan 6, 2018, we screened 1002 girls for eligibility. 72 girls were excluded. 930 girls were enrolled and randomly assigned to receive one dose of Cervarix (155 participants), two doses of Cervarix (155 participants), three doses of Cervarix (155 participants), one dose of Gardasil-9 (155 participants), two doses of Gardasil-9 (155 participants), or three doses of Gardasil-9 (155 participants). 922 participants received all scheduled doses within the defined window (three withdrew, one was lost to follow-up, and one died before completion; two received their 6-month doses early, and one received the wrong valent vaccine in error; all 930 participants were included in the total vaccinated cohort). Retention at 24 months was 918 (99%) of 930 participants. In the according-to-protocol cohort, at 24 months, 99% of participants who received one dose of either HPV vaccine were seropositive for HPV 16 IgG antibodies, compared with 100% of participants who received two doses, and 100% of participants who received three doses. This met the prespecified non-inferiority criteria. Anti-HPV 18 seropositivity at 24 months did not meet non-inferiority criteria for one dose compared to two doses or three doses for either vaccine, although more than 98% of girls in all groups had HPV 18 antibodies. 53 serious adverse events (SAEs) were experienced by 42 (4·5%) of 930 girls, the most common of which was hospital admission for malaria. One girl died of malaria. Number of events was similar between groups and no SAEs were considered related to vaccination. Interpretation: A single dose of the 2-valent or 9-valent HPV vaccine in girls aged 9-14 years induced robust immune responses up to 24 months, suggesting that this reduced dose regimen could be suitable for prevention of HPV infection among girls in the target age group for vaccination. Funding: UK Department for International Development/UK Medical Research Council/Wellcome Trust Joint Global Health Trials Scheme, The Bill & Melinda Gates Foundation, and the US National Cancer Institute. Translation: For the KiSwahili translation of the abstract see Supplementary Materials section. Competing Interests: Declaration of interests DW-J reports a grant from GSK Biologicals in 2007 for a previous study on safety and immunogenicity of Cervarix in Tanzania unrelated to this submitted work. All other authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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