In vivo assembly of epitope-coated biopolymer particles that induce anti-tumor responses
Abstract There is an unmet need for antigen delivery systems that elicit efficient T cell priming to prevent infectious diseases or for treatment of cancers. Here, we explored the immunogenic potential of biologically assembled biopolymer particles (BPs) that have been bioengineered to display the a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00787-8 |
| _version_ | 1797340380398616576 |
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| author | Devi Jenika Saranya Pounraj David Wibowo Leonhard M. Flaxl Bernd H. A. Rehm Justine D. Mintern |
| author_facet | Devi Jenika Saranya Pounraj David Wibowo Leonhard M. Flaxl Bernd H. A. Rehm Justine D. Mintern |
| author_sort | Devi Jenika |
| collection | DOAJ |
| description | Abstract There is an unmet need for antigen delivery systems that elicit efficient T cell priming to prevent infectious diseases or for treatment of cancers. Here, we explored the immunogenic potential of biologically assembled biopolymer particles (BPs) that have been bioengineered to display the antigenic MHC I and MHC II epitopes of model antigen ovalbumin (OVA). Purified dendritic cells (DCs) captured BP-OVA and presented the associated antigenic epitopes to CD4+ T cells and CD8+ T cells. Vaccination with BP-OVA in the absence of adjuvant elicited antigen presentation to OVA-specific CD8+ and CD4+ T cells and cross-primed effective cytotoxic T lymphocyte (CTL) killers. BP-OVA induction of CTL killing did not require CD4+ T cell help, with active CTLs generated in BP-OVA vaccinated I-A b−/− and CD40 −/− mice. In contrast, IL-15 and type I IFN were required, with abrogated CTL activity in vaccinated IL-15 −/− and IFNAR1 −/− mice. cDC1 and/or CD103+ DCs were not essential for BP-OVA specific CTL with immunization eliciting responses in Batf3 −/− mice. Poly I:C, but not LPS or CpG, co-administered as an adjuvant with BP-OVA boosted CTL responses. Finally, vaccination with BP-OVA protected against B16-OVA melanoma and Eμ-myc-GFP-OVA lymphoma inoculation. In summary, we have demonstrated that epitope-displaying BPs represent an antigen delivery platform exhibiting a unique mechanism to effectively engage T cell immune responses. |
| first_indexed | 2024-03-08T10:01:17Z |
| format | Article |
| id | doaj.art-e643f993703c465094e2a0f13d78daee |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-08T10:01:17Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-e643f993703c465094e2a0f13d78daee2024-01-29T10:55:55ZengNature Portfolionpj Vaccines2059-01052024-01-019111110.1038/s41541-023-00787-8In vivo assembly of epitope-coated biopolymer particles that induce anti-tumor responsesDevi Jenika0Saranya Pounraj1David Wibowo2Leonhard M. Flaxl3Bernd H. A. Rehm4Justine D. Mintern5Department of Biochemistry and Pharmacology, The University of Melbourne, Bio21 Molecular Science and Biotechnology InstituteCentre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith UniversityCentre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith UniversityDepartment of Biochemistry and Pharmacology, The University of Melbourne, Bio21 Molecular Science and Biotechnology InstituteCentre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith UniversityDepartment of Biochemistry and Pharmacology, The University of Melbourne, Bio21 Molecular Science and Biotechnology InstituteAbstract There is an unmet need for antigen delivery systems that elicit efficient T cell priming to prevent infectious diseases or for treatment of cancers. Here, we explored the immunogenic potential of biologically assembled biopolymer particles (BPs) that have been bioengineered to display the antigenic MHC I and MHC II epitopes of model antigen ovalbumin (OVA). Purified dendritic cells (DCs) captured BP-OVA and presented the associated antigenic epitopes to CD4+ T cells and CD8+ T cells. Vaccination with BP-OVA in the absence of adjuvant elicited antigen presentation to OVA-specific CD8+ and CD4+ T cells and cross-primed effective cytotoxic T lymphocyte (CTL) killers. BP-OVA induction of CTL killing did not require CD4+ T cell help, with active CTLs generated in BP-OVA vaccinated I-A b−/− and CD40 −/− mice. In contrast, IL-15 and type I IFN were required, with abrogated CTL activity in vaccinated IL-15 −/− and IFNAR1 −/− mice. cDC1 and/or CD103+ DCs were not essential for BP-OVA specific CTL with immunization eliciting responses in Batf3 −/− mice. Poly I:C, but not LPS or CpG, co-administered as an adjuvant with BP-OVA boosted CTL responses. Finally, vaccination with BP-OVA protected against B16-OVA melanoma and Eμ-myc-GFP-OVA lymphoma inoculation. In summary, we have demonstrated that epitope-displaying BPs represent an antigen delivery platform exhibiting a unique mechanism to effectively engage T cell immune responses.https://doi.org/10.1038/s41541-023-00787-8 |
| spellingShingle | Devi Jenika Saranya Pounraj David Wibowo Leonhard M. Flaxl Bernd H. A. Rehm Justine D. Mintern In vivo assembly of epitope-coated biopolymer particles that induce anti-tumor responses npj Vaccines |
| title | In vivo assembly of epitope-coated biopolymer particles that induce anti-tumor responses |
| title_full | In vivo assembly of epitope-coated biopolymer particles that induce anti-tumor responses |
| title_fullStr | In vivo assembly of epitope-coated biopolymer particles that induce anti-tumor responses |
| title_full_unstemmed | In vivo assembly of epitope-coated biopolymer particles that induce anti-tumor responses |
| title_short | In vivo assembly of epitope-coated biopolymer particles that induce anti-tumor responses |
| title_sort | in vivo assembly of epitope coated biopolymer particles that induce anti tumor responses |
| url | https://doi.org/10.1038/s41541-023-00787-8 |
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