Multicomponent intranasal adjuvant for mucosal and durable systemic SARS-CoV-2 immunity in young and aged mice.
Multicomponent intranasal adjuvant for mucosal and durable systemic SARS-CoV-2 immunity in young and aged mice.
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多组分鼻内佐剂用于青年和老年小鼠的黏膜和持久的SARS-CoV-2免疫。
DOI：
10.1038/s41541-023-00691-1
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发表时间：
2023-06-29
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
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作者：
目前，多种 FDA 批准的 SARS-CoV-2 疫苗可以针对严重疾病提供出色的保护。尽管如此，免疫力可能会相对较快地减弱，特别是在老年人中，并且能够逃避感染和疫苗接种诱导的免疫力的新型病毒变种不断出现。鼻内（IN）疫苗接种比肠外疫苗更有效地诱导粘膜免疫反应，这将提高保护作用并减少病毒传播。在这里，我们开发了一种合理设计的 IN 佐剂，由基于纳米乳 (NE) 的组合佐剂和基于 RNA 的 RIG-I 激动剂 (IVT DI) 组成，以驱动更强大、更广泛的保护性抗体和 T 细胞反应。我们之前证明了这种组合佐剂（NE/IVT）通过一系列先天受体的协同激活有效诱导保护性免疫。我们现在证明，具有 SARS-CoV-2 受体结合域 (RBD) 的 NE/IVT 可在年轻和老年小鼠中诱导出同等强度和质量的强大且持久的体液、粘膜和细胞免疫反应。这与 MF59 样肌内佐剂 Addavax 形成鲜明对比，后者的免疫原性随着年龄的增长而降低。在年轻和老年的 NE/IVT 免疫动物中均诱导了强效抗原特异性 IFN-γ/IL-2/TNF-α，这一点很重要，因为它们的产生减少与老年人的保护性免疫力欠佳有关。这些发现凸显了含佐剂的粘膜疫苗在改善针对 COVID-19 的保护方面的潜力。
Multiple FDA-approved SARS-CoV-2 vaccines currently provide excellent protection against severe disease. Despite this, immunity can wane relatively fast, particularly in the elderly and novel viral variants capable of evading infection- and vaccination-induced immunity continue to emerge. Intranasal (IN) vaccination more effectively induces mucosal immune responses than parenteral vaccines, which would improve protection and reduce viral transmission. Here, we developed a rationally designed IN adjuvant consisting of a combined nanoemulsion (NE)-based adjuvant and an RNA-based RIG-I agonist (IVT DI) to drive more robust, broadly protective antibody and T cell responses. We previously demonstrated this combination adjuvant (NE/IVT) potently induces protective immunity through synergistic activation of an array of innate receptors. We now demonstrate that NE/IVT with the SARS-CoV-2 receptor binding domain (RBD), induces robust and durable humoral, mucosal, and cellular immune responses of equivalent magnitude and quality in young and aged mice. This contrasted with the MF59-like intramuscular adjuvant, Addavax, which showed a decrease in immunogenicity with age. Robust antigen-specific IFN-γ/IL-2/TNF-α was induced in both young and aged NE/IVT-immunized animals, which is significant as their reduced production is associated with suboptimal protective immunity in the elderly. These findings highlight the potential of adjuvanted mucosal vaccines for improving protection against COVID-19.
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影响因子：
12.4
作者：
da Silva, Maria Karolaynne;Fulco, Umberto Laino;da Silva Junior, Edilson Dantas;Nobre Oliveira, Jonas Ivan
通讯作者：
Nobre Oliveira, Jonas Ivan
影响因子：
5.5
作者：
Freitag, Tobias L.;Fagerlund, Riku;Karam, Nihay Laham;Leppanen, Veli-Matti;Ugurlu, Hasan;Kant, Ravi;Makinen, Petri;Tawfek, Ahmed;Jha, Sawan Kumar;Strandin, Tomas;Leskinen, Katarzyna;Hepojoki, Jussi;Kesti, Tapio;Kareinen, Lauri;Kuivanen, Suvi;Koivulehto, Emma;Sormunen, Aino;Laidinen, Svetlana;Khattab, Ayman;Saavalainen, Paivi;Meri, Seppo;Kipar, Anja;Sironen, Tarja;Vapalahti, Olli;Alitalo, Kari;Yla-Herttuala, Seppo;Saksela, Kalle
通讯作者：
Saksela, Kalle
影响因子：
4.1
作者：
Herrera NG;Morano NC;Celikgil A;Georgiev GI;Malonis RJ;Lee JH;Tong K;Vergnolle O;Massimi AB;Yen LY;Noble AJ;Kopylov M;Bonanno JB;Garrett-Thomson SC;Hayes DB;Bortz RH 3rd;Wirchnianski AS;Florez C;Laudermilch E;Haslwanter D;Fels JM;Dieterle ME;Jangra RK;Barnhill J;Mengotto A;Kimmel D;Daily JP;Pirofski LA;Chandran K;Brenowitz M;Garforth SJ;Eng ET;Lai JR;Almo SC
通讯作者：
Almo SC
DOI：
10.1056/nejmoa2202261
发表时间：
2022-06-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Collier DA;Ferreira IATM;Kotagiri P;Datir RP;Lim EY;Touizer E;Meng B;Abdullahi A;CITIID-NIHR BioResource COVID-19 Collaboration;Elmer A;Kingston N;Graves B;Le Gresley E;Caputo D;Bergamaschi L;Smith KGC;Bradley JR;Ceron-Gutierrez L;Cortes-Acevedo P;Barcenas-Morales G;Linterman MA;McCoy LE;Davis C;Thomson E;Lyons PA;McKinney E;Doffinger R;Wills M;Gupta RK
通讯作者：
Gupta RK