Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses.

Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses.
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DOI:
10.1038/s41467-022-32149-8
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发表时间:
2022-08-09
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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信使RNA(mRNA)疫苗代表了一种新的、有效的疫苗平台,具有快速开发的高能力。产生具有引发持久、广泛交叉反应性免疫应答潜力的通用流感病毒疫苗对于降低流感相关发病率和死亡率是必要的。本论文主要研究基于脂质纳米颗粒包裹核苷修饰mRNA(mRNA-LNP)平台的通用型B型流感病毒疫苗的开发。我们基于不同的靶抗原评估候选疫苗,这些靶抗原可提供针对来自两种抗原谱系的祖先和最近的流感B病毒的攻击的保护。结合所有测试抗原的五价疫苗在单次接种后以每抗原50 ng的极低剂量保护小鼠免于发病。这些发现支持表达多种保守抗原的核苷修饰的mRNA-LNP作为通用流感病毒疫苗候选物的进一步进展。由B型流感病毒引起的公共卫生问题常常被忽视,但却构成了一个重大的全球负担。在这里,作者基于脂质纳米颗粒包封的核苷修饰的mRNA平台评估了多价疫苗候选物的细胞和体液免疫应答,并证明了对小鼠免受广泛的流感B病毒攻击的保护。
Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates. The public health concern caused by influenza B virus is often overlooked, yet represents a significant global burden. Here, the authors evaluate the cellular and humoral immune responses of multivalent vaccine candidates, based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA platform, and demonstrate protection of mice from challenge with a broad panel of influenza B viruses.
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