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Precise Epitope Organization with Self-adjuvant Framework Nucleic Acid for Efficient COVID-19 Peptide Vaccine Construction
Authors:Dr Fengyun Shen  Zijian Xiong  Dr Yumin Wu  Prof?Dr Rui Peng  Yue Wang  Dr Lele Sun  Prof?Dr Chunhai Fan  Prof?Dr Zhuang Liu
Institution:1. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Lab Carbon Based Functional Materials and Devices, Soochow University, 215123 Suzhou, Jiangsu, China

School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 201240 Shanghai, China

Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), ?Investigation (lead), Methodology (lead), Writing - original draft (lead);2. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Lab Carbon Based Functional Materials and Devices, Soochow University, 215123 Suzhou, Jiangsu, China

Contribution: Data curation (supporting), ?Investigation (equal);3. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Lab Carbon Based Functional Materials and Devices, Soochow University, 215123 Suzhou, Jiangsu, China

Contribution: ?Investigation (supporting), Methodology (supporting);4. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Lab Carbon Based Functional Materials and Devices, Soochow University, 215123 Suzhou, Jiangsu, China

Contribution: Supervision (supporting);5. School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 201240 Shanghai, China

Contribution: Methodology (supporting);6. School of Life Sciences, Shanghai University, 200444 Shanghai, China;7. School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 201240 Shanghai, China

Contribution: Supervision (equal), Writing - review & editing (equal);8. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Lab Carbon Based Functional Materials and Devices, Soochow University, 215123 Suzhou, Jiangsu, China

Abstract:Peptide vaccines have advantages in easy fabrication and high safety, but their effectiveness is hampered by the poor immunogenicity of the epitopes themselves. Herein, we constructed a series of framework nucleic acids (FNAs) with regulated rigidity and size to precisely organize epitopes in order to reveal the influence of epitope spacing and carrier rigidity on the efficiency of peptide vaccines. We found that assembling epitopes on rigid tetrahedral FNAs (tFNAs) with the appropriate size could efficiently enhance their immunogenicity. Further, by integrating epitopes from SARS-CoV-2 on preferred tFNAs, we constructed a COVID-19 peptide vaccine which could induce high titers of IgG against the receptor binding domain (RBD) of SARS-CoV-2 spike protein and increase the ratio of memory B and T cells in mice. Considering the good biocompatibility of tFNAs, our research provides a new idea for developing efficient peptide vaccines against viruses and possibly other diseases.
Keywords:COVID-19  Epitope Organization  Framework Nucleic Acids  Peptide Vaccine
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