Abstract
Safe and effective vaccines are urgently needed to combat the COVID-19 pandemic. However, the SARS-CoV-2 variants raise concerns about the effectiveness of vaccines. As a SARS-CoV-2 antigen target, ORF8 strongly inhibits the IFN-β and NF-κB-responsive promoter, and can be potentially used for the development of SARS-CoV-2 vaccine. However, it is necessary to improve the immunogenicity of ORF8 by adjuvants or delivery systems. CRM 197 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 CRM 197 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 × 10 4 ), 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.
Keywords: CRM(197); ORF8; SARS-CoV-2; Vaccine; eight-arm PEG.
【저자키워드】 SARS-CoV-2, Vaccine, ORF8, CRM(197), eight-arm PEG., 【초록키워드】 IgG, immune response, immunogenicity, Cytokines, Vaccines, COVID-19 pandemic, variant, Toxicity, adjuvants, cytokine, SARS-CoV-2 vaccine, Protein, SARS-CoV-2 variants, ORF8, immune responses, Effectiveness, antigens, adjuvant, humoral immune response, SARS-CoV-2 antigen, liver, IFN-γ, immune protection, TNF-α, T helper cells, cellular, aluminum, proliferation, T helper cell, Conjugates, carrier protein, IFN-β, Effective vaccines, functions, IL-5, BALB/c mice, renal, promoter, conjugation, effective, conjugate, raise, splenocyte, IMPROVE, inhibit, evaluated, activate, effective vaccine, expected, inherent, multiple antigen, the SARS-CoV-2, 【제목키워드】 ORF8 protein, ENhance,