Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents.
Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents.
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DOI：
10.3389/fimmu.2021.772240
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发表时间：
2021
影响因子：
7.3
通讯作者：
Förster R
中科院分区：
文献类型：
--
作者：
Bošnjak B;Odak I;Barros-Martins J;Sandrock I;Hammerschmidt SI;Permanyer M;Patzer GE;Greorgiev H;Gutierrez Jauregui R;Tscherne A;Schwarz JH;Kalodimou G;Ssebyatika G;Ciurkiewicz M;Willenzon S;Bubke A;Ristenpart J;Ritter C;Tuchel T;Meyer Zu Natrup C;Shin DL;Clever S;Limpinsel L;Baumgärtner W;Krey T;Volz A;Sutter G;Förster R
抗原特异性组织驻留记忆T细胞（Trms）和中和伊加抗体提供了最有效的保护肺部免受病毒感染。为了诱导针对SARS-CoV-2的肺免疫的这些基本组分，我们测试了各种免疫方案，包括鼻内递送新型修饰的安卡拉牛痘病毒（MVA）-SARS-2-刺突疫苗候选物。我们表明，一个单一的鼻内MVA-SARS-CoV-2-S的应用程序在小鼠强烈诱导肺刺突特异性的CD 8 + T细胞，虽然限制生产的中和抗体。在初免-加强方案中，鼻内加强疫苗递送被证明对于全身和肺组织驻留的刺突特异性CD 8 + T细胞的大规模扩增以及Th 1-而不是Th 2-CD 4 + T细胞的发育至关重要。同样，血清和支气管肺泡灌洗液中存在非常高滴度的IgG和伊加抗刺突抗体，这些抗体对所有当前关注的SARS-CoV-2变体具有高病毒中和能力。重要的是，在肌内引发和鼻内加强治疗方案中应用的MVA-SARS-2-刺突疫苗完全保护仓鼠免于发生SARS-CoV-2肺部感染和病理。总之，这些结果确定肌内引发，然后用MVA-SARS-2-S进行呼吸道加强，作为诱导局部、呼吸道以及全身免疫应答的有希望的方法，适合于保护免受SARS-CoV-2感染。
Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8+ T cells, albeit restricted production of neutralizing antibodies. In prime-boost protocols, intranasal booster vaccine delivery proved to be crucial for a massive expansion of systemic and lung tissue-resident spike-specific CD8+ T cells and the development of Th1 - but not Th2 - CD4+ T cells. Likewise, very high titers of IgG and IgA anti-spike antibodies were present in serum and broncho-alveolar lavages that possessed high virus neutralization capacities to all current SARS-CoV-2 variants of concern. Importantly, the MVA-SARS-2-spike vaccine applied in intramuscular priming and intranasal boosting treatment regimen completely protected hamsters from developing SARS-CoV-2 lung infection and pathology. Together, these results identify intramuscular priming followed by respiratory tract boosting with MVA-SARS-2-S as a promising approach for the induction of local, respiratory as well as systemic immune responses suited to protect from SARS-CoV-2 infections.
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DOI：
10.1007/978-1-4939-3043-2_17
发表时间：
2016-01-01
期刊：
BACULOVIRUS AND INSECT CELL EXPRESSION PROTOCOLS, 3RD EDITION
影响因子：
--
作者：
Backovic, Marija;Krey, Thomas
通讯作者：
Krey, Thomas
影响因子：
5.4
作者：
Eedara BB;Alabsi W;Encinas-Basurto D;Polt R;Ledford JG;Mansour HM
通讯作者：
Mansour HM
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：
16.6
作者：
Chiuppesi F;Salazar MD;Contreras H;Nguyen VH;Martinez J;Park Y;Nguyen J;Kha M;Iniguez A;Zhou Q;Kaltcheva T;Levytskyy R;Ebelt ND;Kang TH;Wu X;Rogers TF;Manuel ER;Shostak Y;Diamond DJ;Wussow F
通讯作者：
Wussow F
影响因子：
3.7
作者：
Carroll, MW;Moss, B
通讯作者：
Moss, B