tetano
Editor, Senior Moderator
Adv Sci (Weinh)
. 2023 May 10;e2207474.
doi: 10.1002/advs.202207474. Online ahead of print. A Newly Identified Spike Protein Targeted Linear B-Cell Epitope Based Dissolvable Microneedle Array Successfully Eliciting Neutralizing Activities against SARS-CoV-2 Wild-Type Strain in Mice
Lin Li[SUP] 1 [/SUP], Zhongpeng Zhao[SUP] 2 [/SUP], Xiaolan Yang[SUP] 2 [/SUP], Zhongyi Su[SUP] 1 [/SUP], Wendong Li[SUP] 1 [/SUP], Shaolong Chen[SUP] 2 [/SUP], Lu Wang[SUP] 1 [/SUP], Ting Sun[SUP] 1 [/SUP], Chen Du[SUP] 1 [/SUP], Ziyi Li[SUP] 1 [/SUP], Zeqian Yang[SUP] 1 [/SUP], Min Li[SUP] 2 [/SUP], Tiecheng Wang[SUP] 3 [/SUP], Ying Wang[SUP] 1 [/SUP], Yubo Fan[SUP] 1 [/SUP], Hui Wang[SUP] 2 [/SUP], Jing Zhang[SUP] 1 [/SUP]
Affiliations
Vaccination is a cost-effective medical intervention. Inactivated whole virusor large protein fragments-based severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccines have high unnecessary antigenic load to induce allergenicity and/orreactogenicity, which can be avoided by peptide vaccines of short peptide fragments that may induce highly targeted immune response. However, epitope identification and peptide delivery remain the major obstacles in developing peptide vaccines. Here, a multi-source data integrated linear B-cell epitope screening strategy is presented and a linear B-cell epitope enriched hotspot region is identified in Spike protein, from which a monomeric peptide vaccine (Epitope25) is developed and applied to subcutaneously immunize wildtype BALB/c mice. Indirect ELISA assay reveals specific and dose-dependent binding between Epitope25 and serum IgG antibodies from immunized mice. The neutralizing activity of sera from vaccinated mice is validated by pseudo and live SARS-CoV-2 wild-type strain neutralization assays. Then a dissolvable microneedle array (DMNA) is developed to pain-freely deliver Epitope25. Compared with intramuscular injection, DMNA and subcutaneous injection elicit neutralizing activities against SARS-CoV-2 wild-type strain as demonstrated by live SARS-CoV-2 virus neutralization assay. No obvious damages are found in major organs of immunized mice. This study may lay the foundation for developing linear B-cell epitope-based vaccines against SARS-CoV-2.
Keywords: SARS-CoV-2; dissolvable microneedle array; linear B-cell epitope; neutralizing antibody; spike protein.
. 2023 May 10;e2207474.
doi: 10.1002/advs.202207474. Online ahead of print. A Newly Identified Spike Protein Targeted Linear B-Cell Epitope Based Dissolvable Microneedle Array Successfully Eliciting Neutralizing Activities against SARS-CoV-2 Wild-Type Strain in Mice
Lin Li[SUP] 1 [/SUP], Zhongpeng Zhao[SUP] 2 [/SUP], Xiaolan Yang[SUP] 2 [/SUP], Zhongyi Su[SUP] 1 [/SUP], Wendong Li[SUP] 1 [/SUP], Shaolong Chen[SUP] 2 [/SUP], Lu Wang[SUP] 1 [/SUP], Ting Sun[SUP] 1 [/SUP], Chen Du[SUP] 1 [/SUP], Ziyi Li[SUP] 1 [/SUP], Zeqian Yang[SUP] 1 [/SUP], Min Li[SUP] 2 [/SUP], Tiecheng Wang[SUP] 3 [/SUP], Ying Wang[SUP] 1 [/SUP], Yubo Fan[SUP] 1 [/SUP], Hui Wang[SUP] 2 [/SUP], Jing Zhang[SUP] 1 [/SUP]
Affiliations
- PMID: 37162232
- DOI: 10.1002/advs.202207474
Vaccination is a cost-effective medical intervention. Inactivated whole virusor large protein fragments-based severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccines have high unnecessary antigenic load to induce allergenicity and/orreactogenicity, which can be avoided by peptide vaccines of short peptide fragments that may induce highly targeted immune response. However, epitope identification and peptide delivery remain the major obstacles in developing peptide vaccines. Here, a multi-source data integrated linear B-cell epitope screening strategy is presented and a linear B-cell epitope enriched hotspot region is identified in Spike protein, from which a monomeric peptide vaccine (Epitope25) is developed and applied to subcutaneously immunize wildtype BALB/c mice. Indirect ELISA assay reveals specific and dose-dependent binding between Epitope25 and serum IgG antibodies from immunized mice. The neutralizing activity of sera from vaccinated mice is validated by pseudo and live SARS-CoV-2 wild-type strain neutralization assays. Then a dissolvable microneedle array (DMNA) is developed to pain-freely deliver Epitope25. Compared with intramuscular injection, DMNA and subcutaneous injection elicit neutralizing activities against SARS-CoV-2 wild-type strain as demonstrated by live SARS-CoV-2 virus neutralization assay. No obvious damages are found in major organs of immunized mice. This study may lay the foundation for developing linear B-cell epitope-based vaccines against SARS-CoV-2.
Keywords: SARS-CoV-2; dissolvable microneedle array; linear B-cell epitope; neutralizing antibody; spike protein.