Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens
Outer Membrane Vesicles (OMV) constitute a promising platform for the development of efficient vaccines. OMV can be decorated with heterologous antigens (proteins or polysaccharides), becoming attractive novel carriers for the development of multicomponent vaccines. Chemical conjugation represents a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10180 |
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| author | Roberta Di Benedetto Renzo Alfini Martina Carducci Maria Grazia Aruta Luisa Lanzilao Alessandra Acquaviva Elena Palmieri Carlo Giannelli Francesca Necchi Allan Saul Francesca Micoli |
| author_facet | Roberta Di Benedetto Renzo Alfini Martina Carducci Maria Grazia Aruta Luisa Lanzilao Alessandra Acquaviva Elena Palmieri Carlo Giannelli Francesca Necchi Allan Saul Francesca Micoli |
| author_sort | Roberta Di Benedetto |
| collection | DOAJ |
| description | Outer Membrane Vesicles (OMV) constitute a promising platform for the development of efficient vaccines. OMV can be decorated with heterologous antigens (proteins or polysaccharides), becoming attractive novel carriers for the development of multicomponent vaccines. Chemical conjugation represents a tool for linking antigens, also from phylogenetically distant pathogens, to OMV. Here we develop two simple and widely applicable conjugation chemistries targeting proteins or lipopolysaccharides on the surface of Generalized Modules for Membrane Antigens (GMMA), OMV spontaneously released from Gram-negative bacteria mutated to increase vesicle yield and reduce potential reactogenicity. A Design of Experiment approach was used to identify optimal conditions for GMMA activation before conjugation, resulting in consistent processes and ensuring conjugation efficiency. Conjugates produced by both chemistries induced strong humoral response against the heterologous antigen and GMMA. Additionally, the use of the two orthogonal chemistries allowed to control the linkage of two different antigens on the same GMMA particle. This work supports the further advancement of this novel platform with great potential for the design of effective vaccines. |
| first_indexed | 2024-03-10T07:01:00Z |
| format | Article |
| id | doaj.art-b98297759312411dbf3abe6c57a5bd54 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:01:00Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b98297759312411dbf3abe6c57a5bd542023-11-22T16:05:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191018010.3390/ijms221910180Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous AntigensRoberta Di Benedetto0Renzo Alfini1Martina Carducci2Maria Grazia Aruta3Luisa Lanzilao4Alessandra Acquaviva5Elena Palmieri6Carlo Giannelli7Francesca Necchi8Allan Saul9Francesca Micoli10GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyOuter Membrane Vesicles (OMV) constitute a promising platform for the development of efficient vaccines. OMV can be decorated with heterologous antigens (proteins or polysaccharides), becoming attractive novel carriers for the development of multicomponent vaccines. Chemical conjugation represents a tool for linking antigens, also from phylogenetically distant pathogens, to OMV. Here we develop two simple and widely applicable conjugation chemistries targeting proteins or lipopolysaccharides on the surface of Generalized Modules for Membrane Antigens (GMMA), OMV spontaneously released from Gram-negative bacteria mutated to increase vesicle yield and reduce potential reactogenicity. A Design of Experiment approach was used to identify optimal conditions for GMMA activation before conjugation, resulting in consistent processes and ensuring conjugation efficiency. Conjugates produced by both chemistries induced strong humoral response against the heterologous antigen and GMMA. Additionally, the use of the two orthogonal chemistries allowed to control the linkage of two different antigens on the same GMMA particle. This work supports the further advancement of this novel platform with great potential for the design of effective vaccines.https://www.mdpi.com/1422-0067/22/19/10180conjugation chemistryGMMAOMVcarrier proteinvaccineglycoconjugate |
| spellingShingle | Roberta Di Benedetto Renzo Alfini Martina Carducci Maria Grazia Aruta Luisa Lanzilao Alessandra Acquaviva Elena Palmieri Carlo Giannelli Francesca Necchi Allan Saul Francesca Micoli Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens International Journal of Molecular Sciences conjugation chemistry GMMA OMV carrier protein vaccine glycoconjugate |
| title | Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens |
| title_full | Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens |
| title_fullStr | Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens |
| title_full_unstemmed | Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens |
| title_short | Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens |
| title_sort | novel simple conjugation chemistries for decoration of gmma with heterologous antigens |
| topic | conjugation chemistry GMMA OMV carrier protein vaccine glycoconjugate |
| url | https://www.mdpi.com/1422-0067/22/19/10180 |
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