Abstract
SARS-CoV-2 spike (S) variants that may evade antibody-mediated immunity are emerging. Evidence shows that vaccines with a stronger immune response are still effective against mutant strains. Here, we report a targeted type 1 conventional dendritic (cDC1) cell strategy for improved COVID-19 vaccine design. cDC1 cells specifically express X-C motif chemokine receptor 1 (Xcr1), the only receptor for chemokine Xcl1. We fused the S gene sequence with the Xcl1 gene to deliver the expressed S protein to cDC1 cells. Immunization with a plasmid encoding the S protein fused to Xcl1 showed stronger induction of antibody and antigen-specific T cell immune responses than immunization with the S plasmid alone in mice. The fusion gene-induced antibody also displayed more powerful SARS-CoV-2 wild-type virus and pseudovirus neutralizing activity. Xcl1 also increased long-lived antibody-secreting plasma cells in bone marrow. These preliminary results indicate that Xcl1 serves as a molecular adjuvant for the SARS-CoV-2 vaccine and that our Xcl1-S fusion DNA vaccine is a potential COVID-19 vaccine candidate for use in further translational studies.
Highlights
In December 2019, an outbreak of severe pneumonia was reported in Wuhan, China.Scientists identified the virus SARS-CoV-2 as the etiologic cause [1]
As a method to deliver the S protein to cDC1 cells, we used a linker containing 11 amino acids,5-serine-(glycine)5, to fuse the mouse Xcl1 C-terminus to the S protein N-terminus and generate the mXcl1-S protein
As SARS-CoV-2 invades the human body through the respiratory tract, effective distribution of specific antibodies in the lung mucosa could protect against lower respiratory disease (LRD), which could lead to severe cases for COVID-19
Summary
In December 2019, an outbreak of severe pneumonia was reported in Wuhan, China. Scientists identified the virus SARS-CoV-2 as the etiologic cause [1]. The plasmid DNA vaccine paved the way for genetically fusing antigens to antibodies or chemokine ligands to target surface markers on APCs. Previous studies have developed a number of DNA vaccines expressing fusion proteins targeting surface receptors on APCs, such as MHC-II, CCR5, CD40, CD14, and Xcr1 [20–24]. Previous studies have developed a number of DNA vaccines expressing fusion proteins targeting surface receptors on APCs, such as MHC-II, CCR5, CD40, CD14, and Xcr1 [20–24] Immunization with these DNA vaccines enhances immune responses and induces protection against tumor and virus infection. Among these receptors, the Xcr receptor is expressed on cDC1 cells in mice and humans. Xcl1-S DNA vaccine has good immunogenic potential against COVID-19, encouraging future translational studies to contain the current pandemic
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