An mRNA SARS-CoV-2 Vaccine Employing Charge-Altering Releasable Transporters with a TLR-9 Agonist Induces Neutralizing Antibodies and T Cell Memory.
An mRNA SARS-CoV-2 Vaccine Employing Charge-Altering Releasable Transporters with a TLR-9 Agonist Induces Neutralizing Antibodies and T Cell Memory.
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DOI：
10.1021/acscentsci.1c00361
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发表时间：
2021-07-28
影响因子：
18.2
通讯作者：
Levy R
中科院分区：
文献类型：
--
作者：
Haabeth OAW;Lohmeyer JJK;Sallets A;Blake TR;Sagiv-Barfi I;Czerwinski DK;McCarthy B;Powell AE;Wender PA;Waymouth RM;Levy R
SARS-CoV-2大流行需要快速开发预防性疫苗。两种mRNA疫苗已被FDA批准紧急使用，并已证明具有非凡的有效性。这些mRNA疫苗的成功确立了mRNA的开发速度和治疗潜力。这些授权的疫苗编码SARS-CoV-2刺突蛋白的全长版本。它们与具有固有免疫刺激特性的脂质纳米颗粒（LNP）递送载体一起配制。不同的疫苗接种策略和替代的mRNA递送载体将是期望的，以确保未来几代SARS-CoV-2疫苗的灵活性和mRNA疫苗的总体开发。在这里，我们报告了一种替代mRNA疫苗的方法，使用称为电荷改变可释放转运蛋白（CART）的运载工具的发展。使用这些固有的非免疫原性的车辆，我们可以定制疫苗的免疫原性，包括共配制佐剂，如寡脱氧核苷酸与CpG基序（CpG-ODN）。接种mRNA-CART疫苗的小鼠在循环和肺支气管液中产生了治疗相关水平的受体结合结构域（RBD）特异性中和抗体。此外，疫苗接种引起强烈和持久的RBD特异性TH 1 T细胞应答，包括CD 4+和CD 8 + T细胞记忆。改变电荷的可释放转运蛋白有效地递送共配制的SARS-CoV-2 RBD mRNA和佐剂。初免-加强免疫在小鼠中导致稳健的抗原特异性B和T细胞应答。
The SARS-CoV-2 pandemic has necessitated the rapid development of prophylactic vaccines. Two mRNA vaccines have been approved for emergency use by the FDA and have demonstrated extraordinary effectiveness. The success of these mRNA vaccines establishes the speed of development and therapeutic potential of mRNA. These authorized vaccines encode full-length versions of the SARS-CoV-2 spike protein. They are formulated with lipid nanoparticle (LNP) delivery vehicles that have inherent immunostimulatory properties. Different vaccination strategies and alternative mRNA delivery vehicles would be desirable to ensure flexibility of future generations of SARS-CoV-2 vaccines and the development of mRNA vaccines in general. Here, we report on the development of an alternative mRNA vaccine approach using a delivery vehicle called charge-altering releasable transporters (CARTs). Using these inherently nonimmunogenic vehicles, we can tailor the vaccine immunogenicity by inclusion of coformulated adjuvants such as oligodeoxynucleotides with CpG motifs (CpG-ODN). Mice vaccinated with the mRNA-CART vaccine developed therapeutically relevant levels of receptor binding domain (RBD)-specific neutralizing antibodies in both the circulation and in the lung bronchial fluids. In addition, vaccination elicited strong and long-lasting RBD-specific TH1 T cell responses including CD4+ and CD8+ T cell memory. Charge-altering releasable transporters effectively deliver coformulated SARS-CoV-2 RBD mRNA and adjuvant. Prime-boost immunization leads to robust antigen-specific B and T cell responses in mice.
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影响因子：
6.2
作者：
Bode C;Zhao G;Steinhagen F;Kinjo T;Klinman DM
通讯作者：
Klinman DM
DOI：
10.1126/science.abc4730
发表时间：
2020-09-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gu H;Chen Q;Yang G;He L;Fan H;Deng YQ;Wang Y;Teng Y;Zhao Z;Cui Y;Li Y;Li XF;Li J;Zhang NN;Yang X;Chen S;Guo Y;Zhao G;Wang X;Luo DY;Wang H;Yang X;Li Y;Han G;He Y;Zhou X;Geng S;Sheng X;Jiang S;Sun S;Qin CF;Zhou Y
通讯作者：
Zhou Y
影响因子：
7.2
作者：
Grunwitz, Christian;Salomon, Nadja;Sahin, Ugur
通讯作者：
Sahin, Ugur
DOI：
10.1073/pnas.1810002115
发表时间：
2018-09-25
影响因子：
11.1
作者：
Haabeth, Ole A. W.;Blake, Timothy R.;Levy, Ronald
通讯作者：
Levy, Ronald
影响因子：
4.4
作者：
Jung, J;Yi, AK;Choi, YS
通讯作者：
Choi, YS