Genotypic analysis of RTS,S/AS01E malaria vaccine efficacy against parasite infection as a function of dosage regimen and baseline malaria infection status in children aged 5–17 months in Ghana and Kenya: a longitudinal phase 2b randomised controlled trial

作者：Michal Juraska, Angela M. Early, Li Li, S. F. Schaffner, Marc Lievens, Akanksha Khorgade, Brian Simpkins, Nima S. Hejazi, David Benkeser, Qi Wang, Laina D. Mercer, Samuel Adjei, Tsiri Agbenyega, Scott F. Anderson, Daniel Ansong, Dennis K Bii, Patrick Boakye Yiadom Buabeng, Sean English, Nicholas FitzGerald, Jonna Grimsby, Simon Kariuki, Kephas Otieno, François Roman, Aaron M. Samuels, Nelli Westercamp, Christian F. Ockenhouse, Opokua Ofori‐Anyinam, Cynthia Lee, Bronwyn MacInnis, Dyann F. Wirth, Peter B. Gilbert, Daniel E. Neafsey · 发表于：The Lancet Infectious Diseases · 年份：2024 · DOI：10.1016/s1473-3099(24)00179-8 · 被引用次数：17 · 研究领域：Malaria Research and Control、Immune responses and vaccinations、Parasites and Host Interactions

BACKGROUND: , confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy. METHODS: regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291. FINDINGS: regimen significantly reduced the mean number of new infections i...