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; M Gordon Joyce; Kayvon Modjarrad; Jeffrey R Currier; Elke Bergmann-Leitner; Allison M W Malloy; Mangala Rao

doi:10.1038/s41541-021-00414-4

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

NPJ Vaccines. 2021 Dec 13;6(1):151. doi: 10.1038/s41541-021-00414-4.

Authors

Joshua M Carmen^#¹, Shikha Shrivastava^#^{1

2}, Zhongyan Lu^#³, Alexander Anderson^{1

4}, Elaine B Morrison¹, Rajeshwer S Sankhala^{5

6}, Wei-Hung Chen^{5

6}, William C Chang^{5

6}, Jessica S Bolton⁷, Gary R Matyas¹, Nelson L Michael⁸, M Gordon Joyce^{5

6}, Kayvon Modjarrad⁵, Jeffrey R Currier⁹, Elke Bergmann-Leitner⁷, Allison M W Malloy¹⁰, Mangala Rao¹¹

Affiliations

¹ Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
² US Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
³ Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
⁴ Oak Ridge Institute of Science and Education, Oak Ridge, TN, USA.
⁵ Emerging Infectious Diseases Branch, Center of Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁶ Emerging Infectious Diseases Branch, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
⁷ Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁸ Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁹ Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
¹⁰ Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Allison.malloy@usuhs.edu.
¹¹ Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA. mrao@hivresearch.org.

^# Contributed equally.

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.

Abstract

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