SARS-CoV-2 ferritin nanoparticle vaccine induces robust innate immune activity driving polyfunctional spike-specific T cell responses
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, Michael Joyce, Kayvon Modjarrad, Jeffrey R. Currier, Elke S. Bergmann‐Leitner, Allison M. W. Malloy, Mangala Rao
Abstract
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 K b 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.