SARS-CoV-2 ferritin nanoparticle vaccine induces robust innate immune activity driving polyfunctional spike-specific T cell responses.

SARS-CoV-2 ferritin nanoparticle vaccine induces robust innate immune activity driving polyfunctional spike-specific T cell responses.
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DOI:
10.1038/s41541-021-00414-4
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发表时间:
2021-12-13
期刊:
影响因子:
9.2
通讯作者:
Rao M
Rao M
中科院分区:
医学1区
文献类型:
--
作者:
Carmen JM;Shrivastava S;Lu Z;Anderson A;Morrison EB;Sankhala RS;Chen WH;Chang WC;Bolton JS;Matyas GR;Michael NL;Joyce MG;Modjarrad K;Currier JR;Bergmann-Leitner E;Malloy AMW;Rao M

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令人担忧的变异体的出现,其中一些对COVID-19疫苗的敏感性降低,强调了对疫苗设计的理解,以优化有效细胞和体液免疫应答的诱导。我们评估了SARS-CoV-2刺突-铁蛋白纳米颗粒(SpFN)免疫原与两种不同的佐剂(Alhydrogel®或含有QS-21的Army脂质体制剂(ALFQ))配对的独特疫苗诱发的免疫特征。高度活化的多面抗原呈递细胞募集至SpFN+ALFQ接种小鼠的淋巴结与具有有效细胞溶解功能和分布至肺部的多功能刺突特异性记忆CD 4 + T细胞和Kb刺突-(539-546)特异性长寿命记忆CD 8 + T细胞的频率增加相关。SARS-CoV中存在该表位,表明可以诱导产生交叉反应性T细胞以对抗其他冠状病毒株。我们的研究表明,纳米颗粒疫苗与有效参与先天免疫细胞的有效佐剂相结合,可增强SARS-CoV-2特异性持久适应性免疫T细胞反应。
The emergence of variants of concern, some with reduced susceptibility to COVID-19 vaccines underscores consideration for the understanding of vaccine design that optimizes induction of effective cellular and humoral immune responses. We assessed a SARS-CoV-2 spike-ferritin nanoparticle (SpFN) immunogen paired with two distinct adjuvants, Alhydrogel® or Army Liposome Formulation containing QS-21 (ALFQ) for unique vaccine evoked immune signatures. Recruitment of highly activated multifaceted antigen-presenting cells to the lymph nodes of SpFN+ALFQ vaccinated mice was associated with an increased frequency of polyfunctional spike-specific memory CD4+ T cells and Kb spike-(539–546)-specific long-lived memory CD8+ T cells with effective cytolytic function and distribution to the lungs. The presence of this epitope in SARS-CoV, suggests that generation of cross-reactive T cells may be induced against other coronavirus strains. Our study reveals that a nanoparticle vaccine, combined with a potent adjuvant that effectively engages innate immune cells, enhances SARS-CoV-2-specific durable adaptive immune T cell responses.
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