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Novel Synthetic Lipopeptides as Potential Mucosal Adjuvants Enhanced SARS-CoV-2 rRBD-Induced Immune Response. | LitMetric

Novel Synthetic Lipopeptides as Potential Mucosal Adjuvants Enhanced SARS-CoV-2 rRBD-Induced Immune Response.

Front Immunol

National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China.

Published: April 2022

AI Article Synopsis

  • Several lipopeptides have shown potential as vaccine adjuvants by acting as TLR2 agonists and promoting immune responses, although the specifics of their effectiveness are not fully understood.
  • A study synthesized 23 synthetic lipopeptides to evaluate their TLR2 activity and mucosal adjuvant effects, identifying LP1-14, LP1-30, LP1-34, and LP2-2 as particularly effective with lower cytotoxicity compared to the well-known PamCSK.
  • The research indicates that these lipopeptides, particularly LP2-2, enhance the immune response to the SARS-CoV-2 recombinant RBD, suggesting a strong link between lipopeptide structure and TLR2

Article Abstract

As TLR2 agonists, several lipopeptides had been proved to be candidate vaccine adjuvants. In our previous study, lipopeptides mimicking N-terminal structures of the bacterial lipoproteins were also able to promote antigen-specific immune response. However, the structure-activity relationship of lipopeptides as TLR2 agonists is still unclear. Here, 23 synthetic lipopeptides with the same lipid moiety but different peptide sequences were synthesized, and their TLR2 activities and mucosal adjuvant effects to OVA were evaluated. LP1-14, LP1-30, LP1-34 and LP2-2 exhibited significantly lower cytotoxicity and stronger TLR2 activity compared with PamCSK, the latter being one of the most potent TLR2 agonists. LP1-34 and LP2-2 assisted OVA to induce more profound specific IgG in sera or sIgA in BALF than PamCSK. Furthermore, the possibility of LP1-34, LP2-2 and PamCSK as the mucosal adjuvant for the SARS-CoV-2 recombinant RBD (rRBD) was investigated. Intranasally immunized with rRBD plus either the novel lipopeptide or PamCSK significantly increased the levels of specific serum and respiratory mucosal IgG and IgA, while rRBD alone failed to induce specific immune response due to its low immunogenicity. The novel lipopeptides, especially LP2-2, significantly increased levels of rRBD-induced SARS-CoV-2 neutralizing antibody in sera, BALF and nasal wash. Finally, Support vector machine (SVM) results suggested that charged residues in lipopeptides might be beneficial to the agonist activity, while lipophilic residues might adversely affect the agonistic activity. Figuring out the relationship between peptide sequence in the lipopeptide and its TLR2 activity may lay the foundation for the rational design of novel lipopeptide adjuvant for COVID-19 vaccine.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959576PMC
http://dx.doi.org/10.3389/fimmu.2022.833418DOI Listing

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