Phase 2a trial of 0, 1, and 3 month and 0, 7, and 28 day immunization schedules of malaria vaccine RTS,S/AS02 in malaria-naïve adults at the Walter Reed Army Institute of Research

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作者：Kent E. Kester ; James F. Cummings ; Christian F. Ockenhouse ; Robin Nielsen ; B. Ted Hall ; Daniel M. Gordon ; Robert J. Schwenk ; Urszula Krzych ; Carolyn A. Holl ; Gregory Richmond ; Megan G. Dowler ; Jackie
关键词：RTS ; S ; Malaria ; Vaccine ; Falciparum ; Adjuvant System ; AS02 ; Circumsporozoite protein ; Hepatitis B ; Antibody ; Clinical trials ; Rapid immunization ; IFN-γ ; ELISPOT
刊名：Vaccine
出版年：2008
期刊代码：89_0264410x
类别：imm
出版时间：24 April 2008
卷：26
期：18
页码：2191-2202
文件大小：834 K

摘要

We did a randomised, controlled, phase IIb trial of RTS,S/AS02A given at 0, 1, and 2 months in 2022 Mozambican children aged 1–4 years. We previously determined vaccine efficacy (VE) against clinical malaria in a double-blind phase that included study months 2·5–8·5 (VE_2·5–8·5). We now report VE in a single-blind phase up to month 21 (VE_8·5–21). The primary endpoint was time to first or only clinical episode of Plasmodium falciparum malaria (axillary temperature der=0 src="http://www.sciencedirect.com/scidirimg/entities/2a7e.gif" alt="greater-or-equal, slanted" title="greater-or-equal, slanted">37·5°C and P falciparum asexual parasitaemia >2500 per μL) detected through a passive case detection system. We also determined VE for other case definitions and for episodes of severe malaria. This study is registered with the ClinicalTrials.gov identifier NCT00197041.

lass="h4">Findings

During the single-blind phase, VE_(8·5–21) was 28·9%(95%CI 8·4–44·8; p=0·008). At month 21, prevalence of P falciparum infection was 29%lower in the RTS,S/AS02A group than in the control (p=0·017). Considering the entire study period, VE_(2·5–21) was 35·3%(95%CI 21·6–46·6; p<0·0001) and VE_(2·5–21) for severe malaria was 48·6%(95%CI 12·3–71·0; p=0·02).

lass="h4">Interpretation

These results show that RTS,S/AS02A confers partial protection in African children aged 1–4 years living in rural endemic areas against a range of clinical disease caused by P falciparum for at least 18 months, and confirm the potential of malaria vaccines to become credible control tools for public-health use.

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dea71d7dc3ce5fbd05906" onMouseOver="InfoBubble.show('infobubble_3','mlktLink_3')" onMouseOut="InfoBubble.timeout()">Efficacy of the RTS,S/AS02A vaccine against Plasmodium ...
The Lancet

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der=0 src="/scidirimg/jrn_nsub.gif" alt="You are not entitled to access the full text of this document" title="You are not entitled to access the full text of this document" width=12 height=14"> Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial
The Lancet, Volume 364, Issue 9443, 16 October 2004-22 October 2004, Pages 1411-1420
Pedro L Alonso, Jahit Sacarlal, John J Aponte, Amanda Leach, Eusebio Macete, Jessica Milman, Inacio Mandomando, Bart Spiessens, Caterina Guinovart, Mateu Espasa, Quique Bassat, Pedro Aide, Opokua Ofori-Anyinam, Margarita M Navia, Sabine Corachan, Marc Ceuppens, Marie-Claude Dubois, Marie-Ange Demoitié, Filip Dubovsky, Clara Menéndez, et al.

Abstract

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lass="h3">Summary

lass="h4">Background

Development of an effective malaria vaccine could greatly contribute to disease control. RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on Plasmodium falciparum circumsporozoite surface antigen. We aimed to assess vaccine efficacy, immunogenicity, and safety in young African children.

lass="h4">Methods

We did a double-blind, phase IIb, randomised controlled trial in Mozambique in 2022 children aged 1–4 years. The study included two cohorts of children living in two separate areas which underwent different follow-up schemes. Participants were randomly allocated three doses of either RTS,S/AS02A candidate malaria vaccine or control vaccines. The primary endpoint, determined in cohort 1 (n=1605), was time to first clinical episode of P falciparum malaria (axillary temperature ≥37·5°C and P falciparum asexual parasitaemia >2500 per μL) over a 6-month surveillance period. Efficacy for prevention of new infections was determined in cohort 2 (n=417). Analysis was per protocol.

lass="h4">Findings

115 children in cohort 1 and 50 in cohort 2 did not receive all three doses and were excluded from the per-protocol analysis. Vaccine efficacy for the first clinical episodes was 29·9%(95%CI 11·0–44·8; p=0·004). At the end of the 6-month observation period, prevalence of P falciparum infection was 37%lower in the RTS,S/AS02A group compared with the control group (11·9%vs 18·9%; p=0·0003). Vaccine efficacy for severe malaria was 57·7%(95%CI 16·2–80·6; p=0·019). In cohort 2, vaccine efficacy for extending time to first infection was 45·0%(31·4–55·9; p<0·0001).

lass="h4">Interpretation

The RTS,S/AS02A vaccine was safe, well tolerated, and immunogenic. Our results show development of an effective vaccine against malaria is feasible.

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