Abstract：
The emergence of SARS-CoV-2 presents a significant global public health dilemma. Vaccination has long been recognized as the most effective means of preventing the spread of infectious diseases. DNA vaccines have attracted attention due to their safety profile, cost-effectiveness, and ease of production. This study aims to assess the efficacy of plasmid-encoding GM-CSF (pGM-CSF) as an adjuvant to augment the specific humoral and cellular immune response elicited by DNA vaccines based on the receptor-binding domain (RBD) antigen. Compared to the use of plasmid-encoded RBD (pRBD) alone, mice that were immunized with a combination of pRBD and pGM-CSF exhibited significantly elevated levels of RBD-specific antibody titers in serum, BALF, and nasal wash. Furthermore, these mice generated more potent neutralization antibodies against both the wild-type and Omicron pseudovirus, as well as the ancestral virus. In addition, pGM-CSF enhanced pRBD-induced CD4+ and CD8+ T cell responses and promoted central memory T cells storage in the spleen. At the same time, tissue-resident memory T (Trm) cells in the lung also increased significantly, and higher levels of specific responses were maintained 60 days post the final immunization. pGM-CSF may play an adjuvant role by promoting antigen expression, immune cells recruitment and GC B cell responses. In conclusion, pGM-CSF may be an effective adjuvant candidate for the DNA vaccines against SARS-CoV-2.
摘要：
SARS-CoV-2的出现带来了重大的全球公共卫生困境。疫苗接种长期以来被认为是预防传染病传播的最有效手段。DNA疫苗因其安全性而受到关注，成本效益，和易于生产。这项研究旨在评估编码质粒的GM-CSF（pGM-CSF）作为佐剂的功效，以增强基于受体结合域（RBD）抗原的DNA疫苗引起的特异性体液和细胞免疫反应。与单独使用质粒编码的RBD(pRBD)相比，用pRBD和pGM-CSF联合免疫的小鼠表现出血清中RBD特异性抗体滴度的显着升高水平，BALF,和鼻腔清洗。此外，这些小鼠产生了针对野生型和Omicron假病毒的更有效的中和抗体，以及祖先病毒。此外,pGM-CSF增强pRBD诱导的CD4+和CD8+T细胞反应，并促进脾脏中的中枢记忆T细胞储存。同时,肺中的组织驻留记忆T（Trm）细胞也显着增加，在最后一次免疫后60天维持更高水平的特异性应答。pGM-CSF可能通过促进抗原表达发挥佐剂作用，免疫细胞募集和GCB细胞反应。总之,pGM-CSF可能是针对SARS-CoV-2的DNA疫苗的有效佐剂候选物。
