SARS-CoV-2 Ferritin Nanoparticle Vaccine Induces Robust Innate Immune Activity Driving Polyfunctional Spike-specific T Cell Responses

Overview

Journal NPJ Vaccines

Date 2021 Dec 14

PMID 34903722

Citations 41

Authors

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

Affiliations

Soon will be listed here.

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 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.

Citing Articles

TCR transgenic clone selection guided by immune receptor analysis and single-cell RNA expression of polyclonal responders.

Debeuf N, Lameire S, Vanheerswynghels M, Deckers J, De Wolf C, Toussaint W Elife. 2025; 13.

PMID: 39854619 PMC: 11684785. DOI: 10.7554/eLife.98344.

Antigen Delivery Platforms for Next-Generation Coronavirus Vaccines.

Chentoufi A, Ulmer J, BenMohamed L Vaccines (Basel). 2025; 13(1).

PMID: 39852809 PMC: 11769099. DOI: 10.3390/vaccines13010030.

An Evaluation of the Cellular and Humoral Response of a Multi-Epitope Vaccine Candidate Against COVID-19 with Different Alum Adjuvants.

Vega Rojas L, Ruiz-Manzano R, Velasco-Elizondo M, Carbajo-Mata M, Hernandez-Silva D, Rocha-Solache M Pathogens. 2025; 13(12.

PMID: 39770342 PMC: 11728595. DOI: 10.3390/pathogens13121081.

Comparative Analysis of the Neutralizing Capacity of Monovalent and Bivalent Formulations of Betuvax-CoV-2, a Subunit Recombinant COVID-19 Vaccine, Against Various Strains of SARS-CoV-2.

Vakhrusheva A, Romanovskaya-Romanko E, Stukova M, Sukhova M, Kuznetsova K, Kudriavtsev A Vaccines (Basel). 2024; 12(10).

PMID: 39460365 PMC: 11512205. DOI: 10.3390/vaccines12101200.

Ferritin Vaccine Platform for Animal and Zoonotic Viruses.

Ahmadivand S, Fux R, Palic D Vaccines (Basel). 2024; 12(10).

PMID: 39460279 PMC: 11511493. DOI: 10.3390/vaccines12101112.

References

Wrapp D, Wang N, Corbett K, Goldsmith J, Hsieh C, Abiona O . Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020; 367(6483):1260-1263. PMC: 7164637. DOI: 10.1126/science.abb2507. View

Powell A, Zhang K, Sanyal M, Tang S, Weidenbacher P, Li S . A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice. ACS Cent Sci. 2021; 7(1):183-199. PMC: 7805605. DOI: 10.1021/acscentsci.0c01405. View

Genito C, Beck Z, Phares T, Kalle F, Limbach K, Stefaniak M . Liposomes containing monophosphoryl lipid A and QS-21 serve as an effective adjuvant for soluble circumsporozoite protein malaria vaccine FMP013. Vaccine. 2017; 35(31):3865-3874. DOI: 10.1016/j.vaccine.2017.05.070. View

Lowy D, Schiller J . Prophylactic human papillomavirus vaccines. J Clin Invest. 2006; 116(5):1167-73. PMC: 1451224. DOI: 10.1172/JCI28607. View

Logunov D, Dolzhikova I, Zubkova O, Tukhvatullin A, Shcheblyakov D, Dzharullaeva A . Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020; 396(10255):887-897. PMC: 7471804. DOI: 10.1016/S0140-6736(20)31866-3. View

Thompson E, Darrah P, Foulds K, Hoffer E, Caffrey-Carr A, Norenstedt S . Monocytes Acquire the Ability to Prime Tissue-Resident T Cells via IL-10-Mediated TGF-β Release. Cell Rep. 2019; 28(5):1127-1135.e4. PMC: 6825402. DOI: 10.1016/j.celrep.2019.06.087. View

Welsby I, Detienne S, NKuli F, Thomas S, Wouters S, Bechtold V . Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21. Front Immunol. 2017; 7:663. PMC: 5215313. DOI: 10.3389/fimmu.2016.00663. View

Randolph G, Jakubzick C, Qu C . Antigen presentation by monocytes and monocyte-derived cells. Curr Opin Immunol. 2007; 20(1):52-60. PMC: 2408874. DOI: 10.1016/j.coi.2007.10.010. View

Fathman C, Lineberry N . Molecular mechanisms of CD4+ T-cell anergy. Nat Rev Immunol. 2007; 7(8):599-609. DOI: 10.1038/nri2131. View

10.

Kanekiyo M, Wei C, Yassine H, McTamney P, Boyington J, Whittle J . Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature. 2013; 499(7456):102-6. PMC: 8312026. DOI: 10.1038/nature12202. View

11.

Tian J, Patel N, Haupt R, Zhou H, Weston S, Hammond H . SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun. 2021; 12(1):372. PMC: 7809486. DOI: 10.1038/s41467-020-20653-8. View

12.

Bert N, Tan A, Kunasegaran K, Tham C, Hafezi M, Chia A . SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature. 2020; 584(7821):457-462. DOI: 10.1038/s41586-020-2550-z. View

13.

Beck Z, Matyas G, Jalah R, Rao M, Polonis V, Alving C . Differential immune responses to HIV-1 envelope protein induced by liposomal adjuvant formulations containing monophosphoryl lipid A with or without QS21. Vaccine. 2015; 33(42):5578-5587. DOI: 10.1016/j.vaccine.2015.09.001. View

14.

Caserta S, Kleczkowska J, Mondino A, Zamoyska R . Reduced functional avidity promotes central and effector memory CD4 T cell responses to tumor-associated antigens. J Immunol. 2010; 185(11):6545-54. DOI: 10.4049/jimmunol.1001867. View

15.

Ksiazek T, Erdman D, Goldsmith C, Zaki S, Peret T, Emery S . A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003; 348(20):1953-66. DOI: 10.1056/NEJMoa030781. View

16.

Sa Ribero M, Jouvenet N, Dreux M, Nisole S . Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog. 2020; 16(7):e1008737. PMC: 7390284. DOI: 10.1371/journal.ppat.1008737. View

17.

Alving C, Peachman K, Matyas G, Rao M, Beck Z . Army Liposome Formulation (ALF) family of vaccine adjuvants. Expert Rev Vaccines. 2020; 19(3):279-292. PMC: 7412170. DOI: 10.1080/14760584.2020.1745636. View

18.

Jenkins M, Pardoll D, Mizuguchi J, Quill H, Schwartz R . T-cell unresponsiveness in vivo and in vitro: fine specificity of induction and molecular characterization of the unresponsive state. Immunol Rev. 1987; 95:113-35. DOI: 10.1111/j.1600-065x.1987.tb00502.x. View

19.

Roederer M, Nozzi J, Nason M . SPICE: exploration and analysis of post-cytometric complex multivariate datasets. Cytometry A. 2011; 79(2):167-74. PMC: 3072288. DOI: 10.1002/cyto.a.21015. View

20.

De-Simone F, Sariyer R, Otalora Y, Yarandi S, Craigie M, Gordon J . IFN-Gamma Inhibits JC Virus Replication in Glial Cells by Suppressing T-Antigen Expression. PLoS One. 2015; 10(6):e0129694. PMC: 4465661. DOI: 10.1371/journal.pone.0129694. View