Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2.
Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2.
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DOI：
10.1016/j.cell.2022.02.005
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发表时间：
2022-03-03
期刊：
影响因子：
64.5
通讯作者：
Xing Z
中科院分区：
文献类型：
--
作者：
Afkhami S;D'Agostino MR;Zhang A;Stacey HD;Marzok A;Kang A;Singh R;Bavananthasivam J;Ye G;Luo X;Wang F;Ang JC;Zganiacz A;Sankar U;Kazhdan N;Koenig JFE;Phelps A;Gameiro SF;Tang S;Jordana M;Wan Y;Mossman KL;Jeyanathan M;Gillgrass A;Medina MFC;Smaill F;Lichty BD;Miller MS;Xing Z
新兴的 SARS-CoV-2 相关变体 (VOC) 威胁到当前肌肉注射且仅针对刺突蛋白的 COVID-19 疫苗的有效性。迫切需要开发下一代疫苗策略以实现更广泛和持久的保护。使用人类和黑猩猩来源的腺病毒载体 (Ad)，我们在小鼠模型中评估了表达spike-1、核衣壳和 RdRp 抗原的 Ad 载体三价 COVID-19 疫苗。我们表明，单剂量鼻内免疫，特别是黑猩猩 Ad 载体疫苗，在诱导三重保护性免疫方面优于肌肉注射免疫，该三重保护性免疫包括局部和全身抗体反应、粘膜组织驻留记忆 T 细胞和粘膜训练的先天免疫。我们进一步表明，鼻内免疫可以针对祖先 SARS-CoV-2 和两种 VOC（B.1.1.7 和 B.1.351）提供保护。我们的研究结果表明，Ad 载体多价疫苗的呼吸道粘膜递送代表了一种有效的下一代 COVID-19 疫苗策略，可诱导针对当前和未来 VOC 的全方位粘膜免疫。使用表达刺突、核衣壳和 RdRp 抗原的下一代腺病毒载体三价 COVID-19 疫苗进行呼吸道粘膜免疫，通过诱导全身和局部抗体、肺组织驻留记忆 T 细胞和训练有素的肺泡巨噬细胞，诱导针对 SARS-CoV-2 的全方位保护性粘膜免疫。
The emerging SARS-CoV-2 variants of concern (VOCs) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, we evaluated Ad-vectored trivalent COVID-19 vaccines expressing spike-1, nucleocapsid, and RdRp antigens in murine models. We show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. We further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Our findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC. Respiratory mucosal immunization with a next-generation adenoviral-vectored trivalent COVID-19 vaccine expressing spike, nucleocapsid, and RdRp antigens, induces all-around protective mucosal immunity against SARS-CoV-2 via induction of systemic and local antibodies, lung-tissue-resident memory T cells, and trained alveolar macrophages.
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DOI：
10.1016/j.xcrm.2021.100230
发表时间：
2021-04-20
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Hassan AO;Feldmann F;Zhao H;Curiel DT;Okumura A;Tang-Huau TL;Case JB;Meade-White K;Callison J;Chen RE;Lovaglio J;Hanley PW;Scott DP;Fremont DH;Feldmann H;Diamond MS
通讯作者：
Diamond MS
影响因子：
11.8
作者：
Banerjee, Arinjay;Nasir, Jalees A.;Mubareka, Samira
通讯作者：
Mubareka, Samira
影响因子：
64.5
作者：
Garcia-Beltran, Wilfredo F.;Lam, Evan C.;Balazs, Alejandro B.
通讯作者：
Balazs, Alejandro B.
影响因子：
7.5
作者：
Cao H;Mai J;Zhou Z;Li Z;Duan R;Watt J;Chen Z;Bandara RA;Li M;Ahn SK;Poon B;Christie-Holmes N;Gray-Owen SD;Banerjee A;Mossman K;Kozak R;Mubareka S;Rini JM;Hu J;Liu J
通讯作者：
Liu J
影响因子：
82.9
作者：
Amanat F;Stadlbauer D;Strohmeier S;Nguyen THO;Chromikova V;McMahon M;Jiang K;Arunkumar GA;Jurczyszak D;Polanco J;Bermudez-Gonzalez M;Kleiner G;Aydillo T;Miorin L;Fierer DS;Lugo LA;Kojic EM;Stoever J;Liu STH;Cunningham-Rundles C;Felgner PL;Moran T;García-Sastre A;Caplivski D;Cheng AC;Kedzierska K;Vapalahti O;Hepojoki JM;Simon V;Krammer F
通讯作者：
Krammer F