Download This PaperConjugation with 8-Arm PEG and CRM 197 Enhances the Immunogenicity of SARS-CoV-2 ORF8 Protein
23 Pages Posted: 11 Apr 2022
Abstract
The SARS-CoV-2 variants raise concerns about the effectiveness of vaccines. Safe and effective vaccines are urgently needed to combat the COVID-19 pandemic. As a SARS-CoV-2 antigen target, ORF8 strongly inhibits the IFN-β and NF-κB-responsive promoter, which is a potential antigen target for the development of SARS-CoV-2 vaccine. Adjuvants or delivery system were necessitated to improve the immunogenicity of ORF8. CRM197 was a carrier protein with the ability to activate T helper cells for antigens. Eight-arm PEG could conjugate multiple antigen molecules in one entity with inherent adjuvant effect. In the present study, ORF8 was conjugated with CRM197 and 8-arm PEG, respectively. The cellular and humoral immune responses to the conjugates (ORF8-CRM and ORF8-PEG) were evaluated in the BALB/c mice. As compared with ORF8-CRM and ORF8 administrated with aluminum adjuvant (ORF8/AL), ORF8-PEG induced a higher ORF8-specific IgG titer (2.6×104), higher levels of cytokines (IFN-γ, TNF-α, IFN-β, and IL-5), stronger splenocyte proliferation. Thus, conjugation with 8-arm PEG was an effective method to improve the immune response to ORF8. Moreover, ORF8-PEG did not lead to apparent toxicity to the cardiac, liver and renal functions. ORF8-PEG was expected to act as an effective vaccine to provide the immune protection against SARS-CoV-2.
Note:
Funding Information: This study was financially supported by Beijing Natural Science Foundation (M21013), National Natural Science Foundation of China (31970875), and National Key Research and Development Project of China (2018YFA0900804).
Conflict of Interests: None.
Ethical Approval: All procedures of the animal experiments were approved by the Animal Ethical Experimentation Committee of Institute of Process Engineering, Chinese Academy of Sciences (Beijing, China, Permission no. SYXK2019-0004), according to the requirements of the National Act on the Use of Experimental Animals (China).
Keywords: SARS-CoV-2, ORF8, CRM197, eight-arm PEG, vaccine
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