Details

Autor(en) / Beteiligte

• Moon, James E
• Ockenhouse, Christian
• Regules, Jason A
• Vekemans, Johan
• Lee, Cynthia
• Chuang, Ilin
• Traskine, Magali
• Jongert, Erik
• Ivinson, Karen
• Morelle, Danielle
• Komisar, Jack L
• Lievens, Marc
• Sedegah, Martha
• Garver, Lindsey S
• Sikaffy, April K
• Waters, Norman C
• Ballou, William Ripley
• Ofori-Anyinam, Opokua

Titel

A Phase IIa Controlled Human Malaria Infection and Immunogenicity Study of RTS,S/AS01E and RTS,S/AS01B Delayed Fractional Dose Regimens in Malaria-Naive Adults

Ist Teil von

• The Journal of infectious diseases, 2020-10, Vol.222 (10), p.1681-1691

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Background A previous RTS,S/AS01B vaccine challenge trial demonstrated that a 3-dose (0-1-7–month) regimen with a fractional third dose can produce high vaccine efficacy (VE) in adults challenged 3 weeks after vaccination. This study explored the VE of different delayed fractional dose regimens of adult and pediatric RTS,S/AS01 formulations. Methods A total of 130 participants were randomized into 5 groups. Four groups received 3 doses of RTS,S/AS01B or RTS,S/AS01E on a 0-1-7–month schedule, with the final 1 or 2 doses being fractional (one-fifth dose volume). One group received 1 full (month 0) and 1 fractional (month 7) dose of RTS,S/AS01E. Immunized and unvaccinated control participants underwent Plasmodium falciparum–infected mosquito challenge (controlled human malaria infection) 3 months after immunization, a timing chosen to potentially discriminate VEs between groups. Results The VE of 3-dose formulations ranged from 55% (95% confidence interval, 27%–72%) to 76% (48%–89%). Groups administered equivalent formulations of RTS,S/AS01E and RTS,S/AS01B demonstrated comparable VE. The 2-dose group demonstrated lower VE (29% [95% confidence interval, 6%–46%]). All regimens were well tolerated and immunogenic, with trends toward higher anti-circumsporozoite antibody titers in participants protected against infection. Conclusions RTS,S/AS01E can provide VE comparable to an equivalent RTS,S/AS01B regimen in adults, suggesting a universal formulation may be considered. Results also suggest that the 2-dose regimen is inferior to the 3-dose regimens evaluated. Clinical Trial Registration NCT03162614 We explored the ability of different delayed fractional dose-regimens of RTS,S/AS01-formulations to increase vaccine efficacy using CHMI. The pediatric RTS,S/AS01E-formulation was comparably efficacious with an equivalent RTS,S/AS01B regimen in adults. The two-dose regimen evaluated was inferior to the three-dose regimens.