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A spike-ferritin nanoparticle vaccine induces robust innate immune activity and drives polyfunctional SARS-CoV-2-specific T cells

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, View ORCID ProfileElke Bergmann-Leitner, Allison M.W. Malloy, Mangala Rao
doi: https://doi.org/10.1101/2021.04.28.441763
Joshua M. Carmen
1Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD,USA
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Shikha Shrivastava
1Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD,USA
2US Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD,USA
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Zhongyan Lu
3Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD,USA
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Alexander Anderson
1Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD,USA
2US Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD,USA
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Elaine B. Morrison
1Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD,USA
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Rajeshwer S. Sankhala
4Emerging Infectious Diseases Branch, Center of Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD,USA
5Emerging Infectious Diseases Branch, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD,USA
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Wei-Hung Chen
4Emerging Infectious Diseases Branch, Center of Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD,USA
5Emerging Infectious Diseases Branch, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD,USA
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William C. Chang
4Emerging Infectious Diseases Branch, Center of Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD,USA
5Emerging Infectious Diseases Branch, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD,USA
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Jessica S. Bolton
6Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD,USA
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Gary R. Matyas
1Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD,USA
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Nelson L. Michael
7Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD,USA
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M. Gordon Joyce
4Emerging Infectious Diseases Branch, Center of Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD,USA
5Emerging Infectious Diseases Branch, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD,USA
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Kayvon Modjarrad
4Emerging Infectious Diseases Branch, Center of Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD,USA
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Jeffrey R. Currier
8Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD,USA
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Elke Bergmann-Leitner
6Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD,USA
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  • ORCID record for Elke Bergmann-Leitner
Allison M.W. Malloy
3Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD,USA
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  • For correspondence: Allison.malloy@usuhs.edu
Mangala Rao
1Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD,USA
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  • For correspondence: mangala.rao.civ@mail.mil mrao@hivresearch.org
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Abstract

Potent cellular responses to viral infections are pivotal for long -lived protection. Evidence is growing that these responses are critical in SARS -CoV-2 immunity. Assessment of a SARS -CoV-2 spike ferritin nanoparticle (SpFN) immunogen paired with two distinct adjuvants, Alhydrogel® (AH) or Army Liposome Formulation containing QS-21 (ALFQ) demonstrated unique vaccine evoked immune signatures. SpFN+ALFQ enhanced recruitment of highly activated classical and non -classical antigen presenting cells (APCs) to the vaccine-draining lymph nodes of mice. The multifaceted APC response of SpFN+ALFQ vaccinated mice was associated with an increased frequency of polyfunctional spike -specific T cells with a bias towards TH1 responses and more robust SARS-CoV-2 spike-specific recall response. In addition, SpFN+ALFQ induced Kb spike(539-546)-specific memory CD8+ T cells with effective cytolytic function and distribution to the lungs. This epitope is also present in SARS-CoV, thus suggesting that generation of cross-reactive T cells may provide protection against other coronavirus strains. Our study reveals that a nanoparticle vaccine, combined with a potent adjuvant, generates effective SARS-CoV-2 specific innate and adaptive immune T cell responses that are key components to inducing long-lived immunity.

One Sentence Summary SpFN vaccine generates multifactorial cellular immune responses.

Competing Interest Statement

M.G.J and K.M are named as inventors on International Patent Application No. WO/2021/21405 entitled “Vaccines against SARS-CoV-2 and other coronaviruses.” MGJ is named as an inventor on International Patent Application No. WO/2018/081318 and US Patent 10,960,070 entitled “Prefusion Coronavirus Spike Proteins and Their Use.” The other authors declare no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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Posted April 28, 2021.
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A spike-ferritin nanoparticle vaccine induces robust innate immune activity and drives polyfunctional SARS-CoV-2-specific T cells
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
bioRxiv 2021.04.28.441763; doi: https://doi.org/10.1101/2021.04.28.441763
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A spike-ferritin nanoparticle vaccine induces robust innate immune activity and drives polyfunctional SARS-CoV-2-specific T cells
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
bioRxiv 2021.04.28.441763; doi: https://doi.org/10.1101/2021.04.28.441763

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