<i>Neisseria meningitidis</i> Factor H Binding Protein Surface Exposure on <i>Salmonella</i> Typhimurium GMMA Is Critical to Induce an Effective Immune Response against Both Diseases
GMMA, outer membrane vesicles resulting from hyperblebbing mutated bacterial strains, are a versatile vaccine platform for displaying both homologous and heterologous antigens. Periplasmic expression is a popular technique for protein expression in the lumen of the blebs. However, the ability of int...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/10/6/726 |
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| author | Francesca Necchi Giuseppe Stefanetti Renzo Alfini Elena Palmieri Martina Carducci Roberta Di Benedetto Fabiola Schiavo Maria Grazia Aruta Fabiola Giusti Ilaria Ferlenghi Yun Shan Goh Simona Rondini Francesca Micoli |
| author_facet | Francesca Necchi Giuseppe Stefanetti Renzo Alfini Elena Palmieri Martina Carducci Roberta Di Benedetto Fabiola Schiavo Maria Grazia Aruta Fabiola Giusti Ilaria Ferlenghi Yun Shan Goh Simona Rondini Francesca Micoli |
| author_sort | Francesca Necchi |
| collection | DOAJ |
| description | GMMA, outer membrane vesicles resulting from hyperblebbing mutated bacterial strains, are a versatile vaccine platform for displaying both homologous and heterologous antigens. Periplasmic expression is a popular technique for protein expression in the lumen of the blebs. However, the ability of internalized antigens to induce antibody responses has not been extensively investigated. Herein, the <i>Neisseria meningitidis</i> factor H binding protein (fHbp) was heterologously expressed in the lumen of O-antigen positive (OAg+) and O-antigen negative (OAg−) <i>Salmonella</i> Typhimurium GMMA. Only the OAg− GMMA induced an anti-fHbp IgG response in mice if formulated on Alum, although it was weak and much lower compared to the recombinant fHbp. The OAg− GMMA on Alum showed partial instability, with possible exposure of fHbp to the immune system. When we chemically conjugated fHbp to the surface of both OAg+ and OAg− GMMA, these constructs induced a stronger functional response compared to the fHbp immunization alone. Moreover, the OAg+ GMMA construct elicited a strong response against both the target antigens (fHbp and OAg), with no immune interference observed. This result suggests that antigen localization on GMMA surface can play a critical role in the induction of an effective immune response and can encourage the development of GMMA based vaccines delivering key protective antigens on their surface. |
| first_indexed | 2024-03-10T10:35:38Z |
| format | Article |
| id | doaj.art-e5b92a098e244190a436721b35069e81 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T10:35:38Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-e5b92a098e244190a436721b35069e812023-11-21T23:21:51ZengMDPI AGPathogens2076-08172021-06-0110672610.3390/pathogens10060726<i>Neisseria meningitidis</i> Factor H Binding Protein Surface Exposure on <i>Salmonella</i> Typhimurium GMMA Is Critical to Induce an Effective Immune Response against Both DiseasesFrancesca Necchi0Giuseppe Stefanetti1Renzo Alfini2Elena Palmieri3Martina Carducci4Roberta Di Benedetto5Fabiola Schiavo6Maria Grazia Aruta7Fabiola Giusti8Ilaria Ferlenghi9Yun Shan Goh10Simona Rondini11Francesca Micoli12GSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK, 53100 Siena, ItalyGSK, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGMMA, outer membrane vesicles resulting from hyperblebbing mutated bacterial strains, are a versatile vaccine platform for displaying both homologous and heterologous antigens. Periplasmic expression is a popular technique for protein expression in the lumen of the blebs. However, the ability of internalized antigens to induce antibody responses has not been extensively investigated. Herein, the <i>Neisseria meningitidis</i> factor H binding protein (fHbp) was heterologously expressed in the lumen of O-antigen positive (OAg+) and O-antigen negative (OAg−) <i>Salmonella</i> Typhimurium GMMA. Only the OAg− GMMA induced an anti-fHbp IgG response in mice if formulated on Alum, although it was weak and much lower compared to the recombinant fHbp. The OAg− GMMA on Alum showed partial instability, with possible exposure of fHbp to the immune system. When we chemically conjugated fHbp to the surface of both OAg+ and OAg− GMMA, these constructs induced a stronger functional response compared to the fHbp immunization alone. Moreover, the OAg+ GMMA construct elicited a strong response against both the target antigens (fHbp and OAg), with no immune interference observed. This result suggests that antigen localization on GMMA surface can play a critical role in the induction of an effective immune response and can encourage the development of GMMA based vaccines delivering key protective antigens on their surface.https://www.mdpi.com/2076-0817/10/6/726GMMASalmonellaNeisseria meningitidisfHbp |
| spellingShingle | Francesca Necchi Giuseppe Stefanetti Renzo Alfini Elena Palmieri Martina Carducci Roberta Di Benedetto Fabiola Schiavo Maria Grazia Aruta Fabiola Giusti Ilaria Ferlenghi Yun Shan Goh Simona Rondini Francesca Micoli <i>Neisseria meningitidis</i> Factor H Binding Protein Surface Exposure on <i>Salmonella</i> Typhimurium GMMA Is Critical to Induce an Effective Immune Response against Both Diseases Pathogens GMMA Salmonella Neisseria meningitidis fHbp |
| title | <i>Neisseria meningitidis</i> Factor H Binding Protein Surface Exposure on <i>Salmonella</i> Typhimurium GMMA Is Critical to Induce an Effective Immune Response against Both Diseases |
| title_full | <i>Neisseria meningitidis</i> Factor H Binding Protein Surface Exposure on <i>Salmonella</i> Typhimurium GMMA Is Critical to Induce an Effective Immune Response against Both Diseases |
| title_fullStr | <i>Neisseria meningitidis</i> Factor H Binding Protein Surface Exposure on <i>Salmonella</i> Typhimurium GMMA Is Critical to Induce an Effective Immune Response against Both Diseases |
| title_full_unstemmed | <i>Neisseria meningitidis</i> Factor H Binding Protein Surface Exposure on <i>Salmonella</i> Typhimurium GMMA Is Critical to Induce an Effective Immune Response against Both Diseases |
| title_short | <i>Neisseria meningitidis</i> Factor H Binding Protein Surface Exposure on <i>Salmonella</i> Typhimurium GMMA Is Critical to Induce an Effective Immune Response against Both Diseases |
| title_sort | i neisseria meningitidis i factor h binding protein surface exposure on i salmonella i typhimurium gmma is critical to induce an effective immune response against both diseases |
| topic | GMMA Salmonella Neisseria meningitidis fHbp |
| url | https://www.mdpi.com/2076-0817/10/6/726 |
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