Affiliation:
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
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.
Funder
National Key R&D Program of China
National Natural Science Foundation of China
Science and Technology Planning Project of Guangdong Province, China
Shenzhen Science and Technology Program
Sanming Project of Medicine in Shenzhen Nanshan
Subject
Virology,Infectious Diseases
Cited by
3 articles.
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