Oral Immunization with <i>Escherichia coli Nissle 1917</i> Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice
As of October 2022, the COVID-19 pandemic continues to pose a major public health conundrum, with increased rates of symptomatic infections in vaccinated individuals. An ideal vaccine candidate for the prevention of outbreaks should be rapidly scalable, easy to administer, and able to elicit a poten...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/3/569 |
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| author | Giovanni Sarnelli Alessandro Del Re Marcella Pesce Jie Lu Giovanni Esposito Walter Sanseverino Chiara Corpetti Silvia Basili Franzin Luisa Seguella Irene Palenca Sara Rurgo Fatima Domenica Elisa De Palma Aurora Zilli Giuseppe Esposito |
| author_facet | Giovanni Sarnelli Alessandro Del Re Marcella Pesce Jie Lu Giovanni Esposito Walter Sanseverino Chiara Corpetti Silvia Basili Franzin Luisa Seguella Irene Palenca Sara Rurgo Fatima Domenica Elisa De Palma Aurora Zilli Giuseppe Esposito |
| author_sort | Giovanni Sarnelli |
| collection | DOAJ |
| description | As of October 2022, the COVID-19 pandemic continues to pose a major public health conundrum, with increased rates of symptomatic infections in vaccinated individuals. An ideal vaccine candidate for the prevention of outbreaks should be rapidly scalable, easy to administer, and able to elicit a potent mucosal immunity. Towards this aim, we proposed an engineered <i>Escherichia coli</i> (<i>E. coli</i>) <i>Nissle 1917</i> (EcN) strain with SARS-CoV-2 spike protein (SP)-coding plasmid, which was able to expose SP on its cellular surface by a hybridization with the adhesin involved in diffuse adherence 1 (AIDA1). In this study, we presented the effectiveness of a 16-week intragastrically administered, engineered EcN in producing specific systemic and mucosal immunoglobulins against SARS-CoV-2 SP in mice. We observed a time-dependent increase in anti-SARS-CoV-2 SP IgG antibodies in the sera at week 4, with a titre that more than doubled by week 12 and a stable circulating titre by week 16 (+309% and +325% vs. control; both <i>p</i> < 0.001). A parallel rise in mucosal IgA antibody titre in stools, measured via intestinal and bronchoalveolar lavage fluids of the treated mice, reached a plateau by week 12 and until the end of the immunization protocol (+300, +47, and +150%, at week 16; all <i>p</i> < 0.001 vs. controls). If confirmed in animal models of infection, our data indicated that the engineered EcN may be a potential candidate as an oral vaccine against COVID-19. It is safe, inexpensive, and, most importantly, able to stimulate the production of both systemic and mucosal anti-SARS-CoV-2 spike-protein antibodies. |
| first_indexed | 2024-03-11T06:53:04Z |
| format | Article |
| id | doaj.art-e9b4418e855d4f95b4f1df7e80e4c5a7 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T06:53:04Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-e9b4418e855d4f95b4f1df7e80e4c5a72023-11-17T09:53:08ZengMDPI AGBiomolecules2218-273X2023-03-0113356910.3390/biom13030569Oral Immunization with <i>Escherichia coli Nissle 1917</i> Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in MiceGiovanni Sarnelli0Alessandro Del Re1Marcella Pesce2Jie Lu3Giovanni Esposito4Walter Sanseverino5Chiara Corpetti6Silvia Basili Franzin7Luisa Seguella8Irene Palenca9Sara Rurgo10Fatima Domenica Elisa De Palma11Aurora Zilli12Giuseppe Esposito13Department of Clinical Medicine and Surgery, Section of Gastroenterology, University Federico II, 80138 Naples, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Clinical Medicine and Surgery, Section of Gastroenterology, University Federico II, 80138 Naples, ItalyNextbiomics S.R.L. (Società a Responsabilità Limitata), 80100 Naples, ItalyNextbiomics S.R.L. (Società a Responsabilità Limitata), 80100 Naples, ItalyNextbiomics S.R.L. (Società a Responsabilità Limitata), 80100 Naples, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Clinical Medicine and Surgery, Section of Gastroenterology, University Federico II, 80138 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies, Centro Ingegneria Genetica-Biotecnologie Avanzate s.c.a rl, 80131 Naples, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, 00185 Rome, ItalyNextbiomics S.R.L. (Società a Responsabilità Limitata), 80100 Naples, ItalyAs of October 2022, the COVID-19 pandemic continues to pose a major public health conundrum, with increased rates of symptomatic infections in vaccinated individuals. An ideal vaccine candidate for the prevention of outbreaks should be rapidly scalable, easy to administer, and able to elicit a potent mucosal immunity. Towards this aim, we proposed an engineered <i>Escherichia coli</i> (<i>E. coli</i>) <i>Nissle 1917</i> (EcN) strain with SARS-CoV-2 spike protein (SP)-coding plasmid, which was able to expose SP on its cellular surface by a hybridization with the adhesin involved in diffuse adherence 1 (AIDA1). In this study, we presented the effectiveness of a 16-week intragastrically administered, engineered EcN in producing specific systemic and mucosal immunoglobulins against SARS-CoV-2 SP in mice. We observed a time-dependent increase in anti-SARS-CoV-2 SP IgG antibodies in the sera at week 4, with a titre that more than doubled by week 12 and a stable circulating titre by week 16 (+309% and +325% vs. control; both <i>p</i> < 0.001). A parallel rise in mucosal IgA antibody titre in stools, measured via intestinal and bronchoalveolar lavage fluids of the treated mice, reached a plateau by week 12 and until the end of the immunization protocol (+300, +47, and +150%, at week 16; all <i>p</i> < 0.001 vs. controls). If confirmed in animal models of infection, our data indicated that the engineered EcN may be a potential candidate as an oral vaccine against COVID-19. It is safe, inexpensive, and, most importantly, able to stimulate the production of both systemic and mucosal anti-SARS-CoV-2 spike-protein antibodies.https://www.mdpi.com/2218-273X/13/3/569COVID-19engineered probioticsoral vaccineIgA |
| spellingShingle | Giovanni Sarnelli Alessandro Del Re Marcella Pesce Jie Lu Giovanni Esposito Walter Sanseverino Chiara Corpetti Silvia Basili Franzin Luisa Seguella Irene Palenca Sara Rurgo Fatima Domenica Elisa De Palma Aurora Zilli Giuseppe Esposito Oral Immunization with <i>Escherichia coli Nissle 1917</i> Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice Biomolecules COVID-19 engineered probiotics oral vaccine IgA |
| title | Oral Immunization with <i>Escherichia coli Nissle 1917</i> Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice |
| title_full | Oral Immunization with <i>Escherichia coli Nissle 1917</i> Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice |
| title_fullStr | Oral Immunization with <i>Escherichia coli Nissle 1917</i> Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice |
| title_full_unstemmed | Oral Immunization with <i>Escherichia coli Nissle 1917</i> Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice |
| title_short | Oral Immunization with <i>Escherichia coli Nissle 1917</i> Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice |
| title_sort | oral immunization with i escherichia coli nissle 1917 i expressing sars cov 2 spike protein induces mucosal and systemic antibody responses in mice |
| topic | COVID-19 engineered probiotics oral vaccine IgA |
| url | https://www.mdpi.com/2218-273X/13/3/569 |
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