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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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文摘
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 (VE2·5–8·5). We now report VE in a single-blind phase up to month 21 (VE8·5–21). The primary endpoint was time to first or only clinical episode of Plasmodium falciparum malaria (axillary temperature 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.

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).

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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Efficacy of the RTS,S/AS02A vaccine against Plasmodium ...
The Lancet
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

Summary

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.

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.

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).

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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doi:10.1016/j.vaccine.2008.02.048
Published by Elsevier Ltd.

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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