Enhancement of SARS-CoV-2 N Antigen-Specific T Cell Functionality by Modulating the Autophagy-Mediated Signal Pathway in Mice

Wen, Ziyu; Yuan, Yue; Zhao, Yangguo; Wang, Haohang; Han, Zirong; Li, Minchao; Yuan, Jianhui; Sun, Caijun

doi:10.3390/v15061316

Open AccessArticle

Enhancement of SARS-CoV-2 N Antigen-Specific T Cell Functionality by Modulating the Autophagy-Mediated Signal Pathway in Mice

by

Ziyu Wen

^1,†,

Yue Yuan

^1,†,

Yangguo Zhao

¹,

Haohang Wang

¹,

Zirong Han

¹,

Minchao Li

¹,

Jianhui Yuan

^2,* and

Caijun Sun

^1,3,*

¹

School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China

²

Nanshan District Center for Disease Control and Prevention, Shenzhen 518000, China

³

Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou 510080, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Viruses 2023, 15(6), 1316; https://doi.org/10.3390/v15061316

Submission received: 3 May 2023 / Revised: 28 May 2023 / Accepted: 31 May 2023 / Published: 2 June 2023

(This article belongs to the Special Issue Innate Immunity to Virus Infection 2023)

Download

Browse Figures

Versions Notes

Abstract

The frequent SARS-CoV-2 variants have caused a continual challenge, weakening the effectiveness of current vaccines, and thus it is of great importance to induce robust and conserved T cellular immunity for developing the next-generation vaccine against SARS-CoV-2 variants. In this study, we proposed a conception of enhancing the SARS-CoV-2 specific T cell functionality by fusing autophagosome-associated LC3b protein to the nucleocapsid (N) (N-LC3b). When compared to N protein alone, the N-LC3b protein was more effectively targeted to the autophagosome/lysosome/MHC II compartment signal pathway and thus elicited stronger CD4⁺ and CD8⁺ T cell immune responses in mice. Importantly, the frequency of N-specific polyfunctional CD4⁺ and CD8⁺ T cells, which can simultaneously secrete multiple cytokines (IFN-γ⁺/IL-2⁺/TNF-α⁺), in the N-LC3b group was significantly higher than that in the N alone group. Moreover, there was a significantly improved T cell proliferation, especially for CD8⁺ T cells in the N-LC3b group. In addition, the N-LC3b also induced a robust humoral immune response, characterized by the Th1-biased IgG2a subclass antibodies against the SARS-CoV-2 N protein. Overall, these findings demonstrated that our strategy could effectively induce a potential SARS-CoV-2 specific T cellular immunity with enhanced magnitude, polyfunctionality, and proliferation, and thus provided insights to develop a promising strategy for the design of a novel universal vaccine against SARS-CoV-2 variants and other emerging infectious diseases.

Keywords: SARS-CoV-2; N protein; autophagy; T cellular immunity

Share and Cite

MDPI and ACS Style

Wen, Z.; Yuan, Y.; Zhao, Y.; Wang, H.; Han, Z.; Li, M.; Yuan, J.; Sun, C. Enhancement of SARS-CoV-2 N Antigen-Specific T Cell Functionality by Modulating the Autophagy-Mediated Signal Pathway in Mice. Viruses 2023, 15, 1316. https://doi.org/10.3390/v15061316

AMA Style

Wen Z, Yuan Y, Zhao Y, Wang H, Han Z, Li M, Yuan J, Sun C. Enhancement of SARS-CoV-2 N Antigen-Specific T Cell Functionality by Modulating the Autophagy-Mediated Signal Pathway in Mice. Viruses. 2023; 15(6):1316. https://doi.org/10.3390/v15061316

Chicago/Turabian Style

Wen, Ziyu, Yue Yuan, Yangguo Zhao, Haohang Wang, Zirong Han, Minchao Li, Jianhui Yuan, and Caijun Sun. 2023. "Enhancement of SARS-CoV-2 N Antigen-Specific T Cell Functionality by Modulating the Autophagy-Mediated Signal Pathway in Mice" Viruses 15, no. 6: 1316. https://doi.org/10.3390/v15061316

APA Style

Wen, Z., Yuan, Y., Zhao, Y., Wang, H., Han, Z., Li, M., Yuan, J., & Sun, C. (2023). Enhancement of SARS-CoV-2 N Antigen-Specific T Cell Functionality by Modulating the Autophagy-Mediated Signal Pathway in Mice. Viruses, 15(6), 1316. https://doi.org/10.3390/v15061316

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Enhancement of SARS-CoV-2 N Antigen-Specific T Cell Functionality by Modulating the Autophagy-Mediated Signal Pathway in Mice

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI