Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses.
Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses.
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DOI：
10.1073/pnas.2206333119
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发表时间：
2022-11-08
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
在这里，我们已经利用核苷修饰的信使RNA-脂质纳米颗粒（mRNA-LNP）疫苗来递送靶向不同保守蛋白的流感病毒抗原的组合，以诱导具有实质性广度的强烈免疫应答。我们认为这份报告代表了流感病毒疫苗研究的重大进展，因为它描述了一种独特的疫苗接种方法，在单次给药后，该方法可诱导小鼠对多种甲型流感2型血凝素病毒的广泛保护性免疫应答。包含多种保守抗原大大拓宽了针对一组异源（包括禽）流感病毒株的保护的广度和水平。总之，我们的数据表明，mRNA-LNP四价2组流感病毒疫苗是一种有前途的候选疫苗，靶向不同的流感病毒株。不仅靶向血凝素，而且靶向其他流感病毒抗原的组合疫苗制剂可以形成通用流感病毒疫苗的基础，该通用流感病毒疫苗具有引发持久的、广泛的交叉反应性免疫应答的潜力。脂质纳米颗粒（LNP）包裹的信使RNA（mRNA）疫苗可用于用单一疫苗有效靶向多种抗原。在这里，我们评估了核苷修饰的mRNA-LNP疫苗的免疫原性和保护效力，这些疫苗含有四种甲型流感2组病毒抗原（血凝素茎、神经氨酸酶、基质蛋白2和核蛋白）。我们发现，所有的疫苗成分诱导抗原特异性细胞和体液免疫反应后，单剂量管理。虽然单价制剂不是唯一的保护，但组合的四价制剂保护小鼠免受所有攻击病毒，包括相关的H1N1流感病毒1组毒株，体重减轻最小。重要的是，在小鼠中单次接种后，联合疫苗以125 ng/抗原的剂量保护免于发病。根据这些发现，我们确信核苷修饰的mRNA-LNP平台可用于引发针对大量流感病毒的保护。
Here, we have utilized nucleoside-modified messenger RNA-lipid nanoparticle (mRNA-LNP) vaccines to deliver a combination of influenza virus antigens targeting different conserved proteins to induce strong immune responses with substantial breadth. We believe this report represents a major advancement in influenza virus vaccine research as it describes a unique vaccination approach that induces broadly protective immune responses against multiple influenza A group 2 hemagglutinin viruses in mice after administration of a single dose. The inclusion of multiple conserved antigens considerably broadens the breadth and levels of protection against a panel of heterologous (including avian) influenza virus strains. Taken together, our data demonstrate that the mRNA-LNP quadrivalent group 2 influenza virus vaccine is a promising vaccine candidate that targets diverse influenza virus strains. Combined vaccine formulations targeting not only hemagglutinin but also other influenza virus antigens could form the basis for a universal influenza virus vaccine that has the potential to elicit long-lasting, broadly cross-reactive immune responses. Lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) vaccines can be utilized to efficiently target multiple antigens with a single vaccine. Here, we assessed the immunogenicity and protective efficacy of nucleoside-modified mRNA-LNP vaccines that contain four influenza A group 2 virus antigens (hemagglutinin stalk, neuraminidase, matrix protein 2, and nucleoprotein) in mice. We found that all vaccine components induced antigen-specific cellular and humoral immune responses after administration of a single dose. While the monovalent formulations were not exclusively protective, the combined quadrivalent formulation protected mice from all challenge viruses, including a relevant H1N1 influenza virus group 1 strain, with minimal weight loss. Importantly, the combined vaccine protected from morbidity at a dose of 125 ng per antigen after a single vaccination in mice. With these findings, we confidently conclude that the nucleoside-modified mRNA-LNP platform can be used to elicit protection against a large panel of influenza viruses.
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影响因子：
3.7
作者：
Belser, Jessica A.;Johnson, Adam;Tumpey, Terrence M.
通讯作者：
Tumpey, Terrence M.
影响因子：
6.4
作者：
COUCH, RB;KASEL, JA;KILBOURNE, ED
通讯作者：
KILBOURNE, ED
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
3.7
作者：
Easterbrook JD;Schwartzman LM;Gao J;Kash JC;Morens DM;Couzens L;Wan H;Eichelberger MC;Taubenberger JK
通讯作者：
Taubenberger JK
影响因子：
5.5
作者：
John, Shinu;Yuzhakov, Olga;Ciaramella, Giuseppe
通讯作者：
Ciaramella, Giuseppe