cGAMP-adjuvanted multivalent influenza mRNA vaccines induce broadly protective immunity through cutaneous vaccination in mice.
cGAMP-adjuvanted multivalent influenza mRNA vaccines induce broadly protective immunity through cutaneous vaccination in mice.
复制标题
DOI：
10.1016/j.omtn.2022.10.024
复制
发表时间：
2022-12-13
期刊：
影响因子：
--
通讯作者：
Wang, Bao-Zhong
中科院分区：
文献类型：
--
作者：
Zhu, Wandi;Wei, Lai;Dong, Chunhong;Wang, Ye;Kim, Joo;Ma, Yao;Gonzalez, Gilbert X.;Wang, Bao-Zhong
越来越多的临床前和临床结果表明，mRNA 疫苗可以有效预防传染病，并且在动物模型和人类中是安全的。在这项研究中，我们利用 H1N1 和 H3N2 流感病毒的血凝素 mRNA、基质蛋白 1 和核蛋白制备了一种多价流感 mRNA 脂质纳米颗粒 (LNP) 疫苗。我们发现，mRNA LNP 的皮肤免疫诱导了强烈的 Th1 和 Th2 细胞免疫，具有强大的抗原特异性抗体滴度，并增加了分泌细胞因子的脾细胞和抗体分泌细胞。 cGAMP的补充提高了mRNA LNP的免疫原性。与我们研究中的 αGC 或 cGAMP/αGC 佐剂 mRNA LNP 制剂相比，cGAMP mRNA LNP 诱导更强烈的抗体反应。在 cGAMP mRNA LNP 免疫组中观察到，脾脏中 IL-4 和 IFN-γ 分泌细胞和效应记忆 T 细胞群增多，细胞免疫增强，肺中 CD4+ 常驻记忆 (TRM) T 细胞增加。这些结果表明，cGAMP 是小鼠多价 mRNA LNP 疫苗皮肤接种的有效佐剂，可在脾脏和肺中诱导更强的免疫反应，并且 cGAMP 佐剂的 mRNA LNP 可以防止同源和异源病毒感染。佐剂封装的多价 mRNA 脂质纳米颗粒疫苗可诱导强烈的免疫反应，从而在小鼠中产生交叉保护。
Increasing preclinical and clinical results have demonstrated that mRNA vaccines efficiently prevent infectious diseases and are safe in animal models and humans. In this study, we fabricated a multivalent influenza mRNA lipid nanoparticle (LNP) vaccine with mRNAs of hemagglutinins from influenza H1N1 and H3N2 viruses, matrix protein 1, and nucleoprotein. We found that cutaneous immunization with mRNA LNPs induced strong Th1 and Th2 cellular immunity with robust antigen-specific antibody titers and increased cytokine-secreting splenocytes and antibody-secreting cells. The supplement of cGAMP improved the immunogenicity of mRNA LNPs. Compared with αGC or cGAMP/αGC adjuvanted mRNA LNP formulations in our study, cGAMP mRNA LNPs induced more robust antibody responses. Enhanced cellular immunity with more IL-4 and IFN-γ secreting cells and effector memory T cell populations in spleens, as well as increased CD4+ resident memory (TRM) T cells in lungs were observed in cGAMP mRNA LNPs immunized group. These results demonstrated that cGAMP is an effective adjuvant for cutaneous vaccination of multivalent mRNA LNP vaccines in mice to induce stronger immune responses in the spleen and lung, and the cGAMP-adjuvanted mRNA LNPs protected against homologous and heterologous viral infection. Adjuvant encapsulated multivalent mRNA lipid nanoparticle vaccine induces strong immune responses conferring cross-protections in mice.
登录
查看更多内容
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：
7.7
作者：
Chauveau L;Bridgeman A;Tan TK;Beveridge R;Frost JN;Rijal P;Pedroza-Pacheco I;Partridge T;Gilbert-Jaramillo J;Knight ML;Liu X;Russell RA;Borrow P;Drakesmith H;Townsend AR;Rehwinkel J
通讯作者：
Rehwinkel J
影响因子：
5.4
作者：
Heufler, C;Koch, F;Schuler, G
通讯作者：
Schuler, G
影响因子：
--
作者：
Baaten, Bas Jg;Li, Cheng-Rui;Bradley, Linda M
通讯作者：
Bradley, Linda M
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