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

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Joshua M Carmen #, Shikha Shrivastava #, Zhongyan Lu #, Alexander Anderson, Elaine B Morrison, Rajeshwer S Sankhala, Wei-Hung Chen, William C Chang, Jessica S Bolton, Gary R Matyas, Nelson L Michael, M Gordon Joyce, Kayvon Modjarrad, Jeffrey R Currier, Elke Bergmann-Leitner, Allison M W Malloy, Mangala Rao

  • NPJ Vaccines
  • 9.2
  • 2021 Dec 13;6(1):151.
  • 流式
  • 呼吸系统
  • T细胞
  • 新冠
  • γδ T,

Abstract

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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