A synthetic cyclic peptide for promoting antigen presentation and immune activation
Abstract Cyclic peptides are often used as scaffolds for the multivalent presentation of drug molecules due to their structural stability and constrained conformation. We identified a cyclic deca-peptide incorporating lipoamino acids for delivering T helper and B cell epitopes against group A Strept...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-024-01050-4 |
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| author | Jiahui Zhang Harrison Y. R. Madge Asmaa Mahmoud Lantian Lu Wanyi Wang Wenbin Huang Prashamsa Koirala Jazmina L. Gonzalez Cruz Wei Yang Kong Sahra Bashiri Ahmed O. Shalash Waleed M. Hussein Zeinab G. Khalil James W. Wells Istvan Toth Rachel J. Stephenson |
| author_facet | Jiahui Zhang Harrison Y. R. Madge Asmaa Mahmoud Lantian Lu Wanyi Wang Wenbin Huang Prashamsa Koirala Jazmina L. Gonzalez Cruz Wei Yang Kong Sahra Bashiri Ahmed O. Shalash Waleed M. Hussein Zeinab G. Khalil James W. Wells Istvan Toth Rachel J. Stephenson |
| author_sort | Jiahui Zhang |
| collection | DOAJ |
| description | Abstract Cyclic peptides are often used as scaffolds for the multivalent presentation of drug molecules due to their structural stability and constrained conformation. We identified a cyclic deca-peptide incorporating lipoamino acids for delivering T helper and B cell epitopes against group A Streptococcus (GAS), eliciting robust humoral immune responses. In this study, we assessed the function-immunogenicity relationship of the multi-component vaccine candidate (referred to as VC-13) to elucidate a mechanism of action. We identified a potential universal delivery platform, not only capable of adjuvanting different peptide epitopes (e.g., NS1 and 88/30 from group A Streptococcus, gonadotropin hormone releasing hormone [GnRH]), but also protein antigens (e.g., bovine serum albumin [BSA], receptor binding domain (RBD) of the SARS-CoV-2 protein responsible for COVID-19 infection [SARS-CoV-2 RBD]) and small molecular haptens (e.g., cocaine). All vaccine candidates self-assembled into sub-500 nm nanoparticles and induced high antigen-specific systemic IgG titers and opsonic potential compared to the antigen co-administered with a commercial adjuvant, complete Freund’s adjuvant. Notably, presence of the cyclic decapeptide in this vaccine increased accumulation in the draining inguinal lymph nodes, facilitating cellular uptake of peptide antigens. Furthermore, the lipoamino acid promoted dendritic cell activation, acting as both toll-like receptors 2 and 4 -targeting moiety. Our study revealed the importance of the cyclic decapeptide and lipoamino acid presence in antigen presentation and immune response activation, leading onto the development of a fully synthetic, self-assembled, and promising platform for the delivery of subunit vaccines and anti-drug vaccines. |
| format | Article |
| id | doaj-art-80c59d6d3f66411886425a81320832d1 |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-80c59d6d3f66411886425a81320832d12025-01-19T12:09:17ZengNature Portfolionpj Vaccines2059-01052025-01-0110111310.1038/s41541-024-01050-4A synthetic cyclic peptide for promoting antigen presentation and immune activationJiahui Zhang0Harrison Y. R. Madge1Asmaa Mahmoud2Lantian Lu3Wanyi Wang4Wenbin Huang5Prashamsa Koirala6Jazmina L. Gonzalez Cruz7Wei Yang Kong8Sahra Bashiri9Ahmed O. Shalash10Waleed M. Hussein11Zeinab G. Khalil12James W. Wells13Istvan Toth14Rachel J. Stephenson15School of Chemistry and Molecular Biosciences, The University of QueenslandSchool of Chemistry and Molecular Biosciences, The University of QueenslandSchool of Chemistry and Molecular Biosciences, The University of QueenslandSchool of Chemistry and Molecular Biosciences, The University of QueenslandSchool of Chemistry and Molecular Biosciences, The University of QueenslandSchool of Chemistry and Molecular Biosciences, The University of QueenslandSchool of Chemistry and Molecular Biosciences, The University of QueenslandFaculty of Medicine, Frazer Institute, The University of QueenslandFaculty of Medicine, Frazer Institute, The University of QueenslandSchool of Chemistry and Molecular Biosciences, The University of QueenslandSchool of Chemistry and Molecular Biosciences, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandFaculty of Medicine, Frazer Institute, The University of QueenslandSchool of Chemistry and Molecular Biosciences, The University of QueenslandSchool of Chemistry and Molecular Biosciences, The University of QueenslandAbstract Cyclic peptides are often used as scaffolds for the multivalent presentation of drug molecules due to their structural stability and constrained conformation. We identified a cyclic deca-peptide incorporating lipoamino acids for delivering T helper and B cell epitopes against group A Streptococcus (GAS), eliciting robust humoral immune responses. In this study, we assessed the function-immunogenicity relationship of the multi-component vaccine candidate (referred to as VC-13) to elucidate a mechanism of action. We identified a potential universal delivery platform, not only capable of adjuvanting different peptide epitopes (e.g., NS1 and 88/30 from group A Streptococcus, gonadotropin hormone releasing hormone [GnRH]), but also protein antigens (e.g., bovine serum albumin [BSA], receptor binding domain (RBD) of the SARS-CoV-2 protein responsible for COVID-19 infection [SARS-CoV-2 RBD]) and small molecular haptens (e.g., cocaine). All vaccine candidates self-assembled into sub-500 nm nanoparticles and induced high antigen-specific systemic IgG titers and opsonic potential compared to the antigen co-administered with a commercial adjuvant, complete Freund’s adjuvant. Notably, presence of the cyclic decapeptide in this vaccine increased accumulation in the draining inguinal lymph nodes, facilitating cellular uptake of peptide antigens. Furthermore, the lipoamino acid promoted dendritic cell activation, acting as both toll-like receptors 2 and 4 -targeting moiety. Our study revealed the importance of the cyclic decapeptide and lipoamino acid presence in antigen presentation and immune response activation, leading onto the development of a fully synthetic, self-assembled, and promising platform for the delivery of subunit vaccines and anti-drug vaccines.https://doi.org/10.1038/s41541-024-01050-4 |
| spellingShingle | Jiahui Zhang Harrison Y. R. Madge Asmaa Mahmoud Lantian Lu Wanyi Wang Wenbin Huang Prashamsa Koirala Jazmina L. Gonzalez Cruz Wei Yang Kong Sahra Bashiri Ahmed O. Shalash Waleed M. Hussein Zeinab G. Khalil James W. Wells Istvan Toth Rachel J. Stephenson A synthetic cyclic peptide for promoting antigen presentation and immune activation npj Vaccines |
| title | A synthetic cyclic peptide for promoting antigen presentation and immune activation |
| title_full | A synthetic cyclic peptide for promoting antigen presentation and immune activation |
| title_fullStr | A synthetic cyclic peptide for promoting antigen presentation and immune activation |
| title_full_unstemmed | A synthetic cyclic peptide for promoting antigen presentation and immune activation |
| title_short | A synthetic cyclic peptide for promoting antigen presentation and immune activation |
| title_sort | synthetic cyclic peptide for promoting antigen presentation and immune activation |
| url | https://doi.org/10.1038/s41541-024-01050-4 |
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