Alonso Pedro L, Sacarlal Jahit, Aponte John J, Leach Amanda, Macete Eusebio, Aide Pedro, Sigauque Betuel, Milman Jessica, Mandomando Inacio, Bassat Quique, Guinovart Caterina, Espasa Mateu, Corachan Sabine, Lievens Marc, Navia Margarita M, Dubois Marie-Claude, Menendez Clara, Dubovsky Filip, Cohen Joe, Thompson Ricardo, Ballou W Ripley
Centre de Salut Internacional, Hospital Clínic/ Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Villarroel 170, 08036 Barcelona, Spain.
Lancet. 2005 Dec 10;366(9502):2012-8. doi: 10.1016/S0140-6736(05)67669-6.
RTS,S/AS02A is a pre-erythrocytic stage malaria vaccine that provides partial protection against infection in malaria-naive adult volunteers and hyperimmune adults. A previous report showed that this vaccine reduced risk of clinical malaria, delayed time to new infection, and reduced episodes of severe malaria over 6 months in African children. An important remaining issue is the durability of protection against clinical disease in these children.
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 37.5 degrees C and P falciparum asexual parasitaemia >2500 per microL) 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.
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).
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.
RTS,S/AS02A是一种疟原虫前体阶段疟疾疫苗，可在未感染过疟疾的成年志愿者和超免疫成年人中提供部分感染防护。此前一份报告显示，该疫苗可降低非洲儿童临床疟疾风险、延迟新感染时间，并减少6个月内的严重疟疾发作次数。这些儿童中针对临床疾病的保护持久性仍是一个重要的遗留问题。
我们在2022年对1至4岁的莫桑比克儿童进行了一项随机、对照、IIb期试验，在0、1和2个月时接种RTS,S/AS02A。我们之前在一个双盲阶段（包括研究的第2.5至8.5个月）确定了该疫苗针对临床疟疾的疫苗效力（VE(2.5 - 8.5)）。我们现在报告直至第21个月的单盲阶段的VE(8.5 - 21)。主要终点是通过被动病例检测系统检测到的首次或仅有的恶性疟原虫疟疾临床发作时间（腋窝温度37.5摄氏度且恶性疟原虫无性体血症>每微升2500个）。我们还确定了针对其他病例定义和严重疟疾发作的VE。本研究已在ClinicalTrials.gov注册，标识符为NCT00197041。
在单盲阶段，VE(8.5 - 21)为28.9%（95%置信区间8.4 - 44.8；p = 0.008）。在第21个月时，RTS,S/AS02A组的恶性疟原虫感染患病率比对照组低29%（p = 0.017）。考虑整个研究期，VE(2.5 - 21)为35.3%（95%置信区间21.6 - 46.6；p < 0.0001），针对严重疟疾的VE(2.5 - 21)为48.6%（95%置信区间12.3 - 71.0；p = 0.02）。
这些结果表明，RTS,S/AS02A可为生活在农村流行地区的1至4岁非洲儿童提供针对由恶性疟原虫引起的一系列临床疾病的部分保护，为期至少18个月，并证实了疟疾疫苗成为可靠的公共卫生控制工具的潜力。
