pGM-CSF as an adjuvant in DNA vaccination against SARS-CoV-2

• Published in: International journal of biological macromolecules 2024-04, Vol.264 (Pt 2), p.130660-130660, Article 130660
• Main Authors: Liu, Chang, Xue, Ruo-Yi, Li, Guo-Cheng, Zhang, Yi, Wu, Wei-Yi, Liu, Jing-Yi, Feng, Rang, Jin, Zhe, Deng, Yan, Jin, Zi-Li, Cheng, Hao, Mao, Ling, Zou, Quan-Ming, Li, Hai-Bo
• Format: Article
• Language: English
• Subjects: Adjuvant; adjuvants; Adjuvants, Immunologic - pharmacology; Adjuvants, Pharmaceutic; Animals; antibodies; Antibodies, Neutralizing; Antibodies, Viral; antigens; B-lymphocytes; blood serum; cell-mediated immunity; cost effectiveness; COVID-19 - prevention & control; COVID-19 Vaccines; DNA; DNA vaccine; GM-CSF; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; lungs; Mice; neutralization; nose; Pseudovirus; public health; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; spleen; T-lymphocytes; Vaccination; Vaccines, DNA; viruses
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.130660

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. [Display omitted] •pGM-CSF enhanced the specific humoral and cellular immune response of RBD antigen-based DNA vaccines.•pRBD plus pGM-CSF induced robust neutralization antibodies against wild-type and Omicron pseudovirus and authentic virus.•pGM-CSF promoted Tcm storage in the spleen and Trm in the lung tissue.•pGM-CSF may play an adjuvant role by promoting antigen expression, immune cells recruitment and GC B cell responses.