mRNA-LNP expressing PfCSP and Pfs25 vaccine candidates targeting infection and transmission of Plasmodium falciparum.
mRNA-LNP expressing PfCSP and Pfs25 vaccine candidates targeting infection and transmission of Plasmodium falciparum.
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DOI：
10.1038/s41541-022-00577-8
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发表时间：
2022-12-01
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
--
作者：
疟疾是一种致命疾病，每年导致 550,000 至 627,000 人死亡。迫切需要开发旨在消除疟疾的疫苗。恶性疟原虫复杂的生命周期不仅提供了针对由按蚊引入的传染性子孢子阶段的机会，而且还提供了针对有性阶段的机会，该阶段被蚊子在吸血期间摄入，导致寄生虫传播。人们普遍认为，针对多个阶段的疫苗会诱导有效的传播，从而降低免疫力。技术进步提供了新的疫苗平台，例如 mRNA-LNP，可用于开发高效的疟疾疫苗。我们评估了两种主要的恶性疟原虫候选疫苗 Pfs25 和 PfCSP（以 mRNA-LNP 疫苗形式提供）的免疫原性。两种疫苗单独或联合给药时均能诱导极其有效的免疫反应，优于 Pfs25 和 PfCSP DNA 疫苗配方。来自 Pfs25 mRNA-LNP 免疫小鼠的纯化 IgG 在减少疟疾传播给蚊子方面非常有效。此外，用 PfCSP mRNA-LNP 免疫三次和四次后的小鼠提供了针对子孢子攻击的不同程度的保护的证据。对单独或联合施用的每种 mRNA-LNP 疫苗诱导的免疫反应和阶段特异性功能活性的比较也支持开发有效的组合疫苗，而不会产生任何免疫干扰的风险，以针对不同生命周期阶段的疟疾寄生虫。针对感染阶段和性/中肠阶段的疫苗组合预计将阻断疟疾传播，这对于实现消除目标至关重要。
Malaria is a deadly disease responsible for between 550,000 and 627,000 deaths annually. There is a pressing need to develop vaccines focused on malaria elimination. The complex lifecycle of Plasmodium falciparum provides opportunities not only to target the infectious sporozoite stage, introduced by anopheline mosquitoes, but also the sexual stages, which are ingested by mosquitoes during blood feeding, leading to parasite transmission. It is widely recognized that a vaccine targeting multiple stages would induce efficacious transmission reducing immunity. Technological advancements offer new vaccine platforms, such as mRNA-LNPs, which can be used to develop highly effective malarial vaccines. We evaluated the immunogenicity of two leading P. falciparum vaccine candidates, Pfs25 and PfCSP, delivered as mRNA-LNP vaccines. Both vaccines induced extremely potent immune responses when administered alone or in combination, which were superior to Pfs25 and PfCSP DNA vaccine formulations. Purified IgGs from Pfs25 mRNA-LNPs immunized mice were highly potent in reducing malaria transmission to mosquitoes. Additionally, mice after three and four immunizations with PfCSP mRNA-LNP provided evidence for varying degrees of protection against sporozoite challenge. The comparison of immune responses and stage-specific functional activity induced by each mRNA-LNP vaccine, administered alone or in combination, also supports the development of an effective combination vaccine without any risk of immune interference for targeting malaria parasites at various life cycle stages. A combination of vaccines targeting both the infective stage and sexual/midgut stages is expected to interrupt malaria transmission, which is critical for achieving elimination goals.
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影响因子：
32.4
作者：
Alameh MG;Tombácz I;Bettini E;Lederer K;Sittplangkoon C;Wilmore JR;Gaudette BT;Soliman OY;Pine M;Hicks P;Manzoni TB;Knox JJ;Johnson JL;Laczkó D;Muramatsu H;Davis B;Meng W;Rosenfeld AM;Strohmeier S;Lin PJC;Mui BL;Tam YK;Karikó K;Jacquet A;Krammer F;Bates P;Cancro MP;Weissman D;Luning Prak ET;Allman D;Locci M;Pardi N
通讯作者：
Pardi N
影响因子：
7.3
作者：
Brod, Florian;Miura, Kazutoyo;Biswas, Sumi
通讯作者：
Biswas, Sumi
影响因子：
7.8
作者：
Buschmann MD;Carrasco MJ;Alishetty S;Paige M;Alameh MG;Weissman D
通讯作者：
Weissman D
影响因子：
3.1
作者：
Ferraro, B.;Talbott, K. T.;Weiner, D. B.
通讯作者：
Weiner, D. B.
影响因子：
3.7
作者：
Boes A;Spiegel H;Voepel N;Edgue G;Beiss V;Kapelski S;Fendel R;Scheuermayer M;Pradel G;Bolscher JM;Behet MC;Dechering KJ;Hermsen CC;Sauerwein RW;Schillberg S;Reimann A;Fischer R
通讯作者：
Fischer R