Potential of Nucleic Acid Receptor Ligands to Improve Vaccination Efficacy against the Filarial Nematode <i>Litomosoides sigmodontis</i>
More than two-hundred-million people are infected with filariae worldwide. However, there is no vaccine available that confers long-lasting protection against filarial infections. Previous studies indicated that vaccination with irradiated infective L3 larvae reduces the worm load. This present stud...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/5/966 |
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| author | Johanna F. Scheunemann Frederic Risch Julia J. Reichwald Benjamin Lenz Anna-Lena Neumann Stephan Garbe Stefan J. Frohberger Marianne Koschel Jesuthas Ajendra Maximilian Rothe Eicke Latz Christoph Coch Gunther Hartmann Beatrix Schumak Achim Hoerauf Marc P. Hübner |
| author_facet | Johanna F. Scheunemann Frederic Risch Julia J. Reichwald Benjamin Lenz Anna-Lena Neumann Stephan Garbe Stefan J. Frohberger Marianne Koschel Jesuthas Ajendra Maximilian Rothe Eicke Latz Christoph Coch Gunther Hartmann Beatrix Schumak Achim Hoerauf Marc P. Hübner |
| author_sort | Johanna F. Scheunemann |
| collection | DOAJ |
| description | More than two-hundred-million people are infected with filariae worldwide. However, there is no vaccine available that confers long-lasting protection against filarial infections. Previous studies indicated that vaccination with irradiated infective L3 larvae reduces the worm load. This present study investigated whether the additional activation of cytosolic nucleic acid receptors as an adjuvant improves the efficacy of vaccination with irradiated L3 larvae of the rodent filaria <i>Litomosoides sigmodontis</i> with the aim of identifying novel vaccination strategies for filarial infections. Subcutaneous injection of irradiated L3 larvae in combination with poly(I:C) or 3pRNA resulted in neutrophil recruitment to the skin, accompanied by higher IP-10/CXCL10 and IFN-β RNA levels. To investigate the impact on parasite clearance, BALB/c mice received three subcutaneous injections in 2-week intervals with irradiated L3 larvae in combination with poly(I:C) or 3pRNA prior to the challenge infection. Vaccination with irradiated L3 larvae in combination with poly(I:C) or 3pRNA led to a markedly greater reduction in adult-worm counts by 73% and 57%, respectively, compared to the immunization with irradiated L3 larvae alone (45%). In conclusion, activation of nucleic acid-sensing immune receptors boosts the protective immune response against <i>L. sigmodontis</i> and nucleic acid-receptor agonists as vaccine adjuvants represent a promising novel strategy to improve the efficacy of vaccines against filariae and potentially other helminths. |
| first_indexed | 2024-03-11T03:15:43Z |
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| id | doaj.art-b87d9cd8fe334b3eaac4ac43de97300f |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T03:15:43Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-b87d9cd8fe334b3eaac4ac43de97300f2023-11-18T03:36:25ZengMDPI AGVaccines2076-393X2023-05-0111596610.3390/vaccines11050966Potential of Nucleic Acid Receptor Ligands to Improve Vaccination Efficacy against the Filarial Nematode <i>Litomosoides sigmodontis</i>Johanna F. Scheunemann0Frederic Risch1Julia J. Reichwald2Benjamin Lenz3Anna-Lena Neumann4Stephan Garbe5Stefan J. Frohberger6Marianne Koschel7Jesuthas Ajendra8Maximilian Rothe9Eicke Latz10Christoph Coch11Gunther Hartmann12Beatrix Schumak13Achim Hoerauf14Marc P. Hübner15Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, GermanyClinic for Radiotherapy and Radiation Oncology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Innate Immunity, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Innate Immunity, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, GermanyMore than two-hundred-million people are infected with filariae worldwide. However, there is no vaccine available that confers long-lasting protection against filarial infections. Previous studies indicated that vaccination with irradiated infective L3 larvae reduces the worm load. This present study investigated whether the additional activation of cytosolic nucleic acid receptors as an adjuvant improves the efficacy of vaccination with irradiated L3 larvae of the rodent filaria <i>Litomosoides sigmodontis</i> with the aim of identifying novel vaccination strategies for filarial infections. Subcutaneous injection of irradiated L3 larvae in combination with poly(I:C) or 3pRNA resulted in neutrophil recruitment to the skin, accompanied by higher IP-10/CXCL10 and IFN-β RNA levels. To investigate the impact on parasite clearance, BALB/c mice received three subcutaneous injections in 2-week intervals with irradiated L3 larvae in combination with poly(I:C) or 3pRNA prior to the challenge infection. Vaccination with irradiated L3 larvae in combination with poly(I:C) or 3pRNA led to a markedly greater reduction in adult-worm counts by 73% and 57%, respectively, compared to the immunization with irradiated L3 larvae alone (45%). In conclusion, activation of nucleic acid-sensing immune receptors boosts the protective immune response against <i>L. sigmodontis</i> and nucleic acid-receptor agonists as vaccine adjuvants represent a promising novel strategy to improve the efficacy of vaccines against filariae and potentially other helminths.https://www.mdpi.com/2076-393X/11/5/966filariae<i>Litomosoides sigmodontis</i>3pRNApoly(I:C)vaccinationnucleic acid receptor |
| spellingShingle | Johanna F. Scheunemann Frederic Risch Julia J. Reichwald Benjamin Lenz Anna-Lena Neumann Stephan Garbe Stefan J. Frohberger Marianne Koschel Jesuthas Ajendra Maximilian Rothe Eicke Latz Christoph Coch Gunther Hartmann Beatrix Schumak Achim Hoerauf Marc P. Hübner Potential of Nucleic Acid Receptor Ligands to Improve Vaccination Efficacy against the Filarial Nematode <i>Litomosoides sigmodontis</i> Vaccines filariae <i>Litomosoides sigmodontis</i> 3pRNA poly(I:C) vaccination nucleic acid receptor |
| title | Potential of Nucleic Acid Receptor Ligands to Improve Vaccination Efficacy against the Filarial Nematode <i>Litomosoides sigmodontis</i> |
| title_full | Potential of Nucleic Acid Receptor Ligands to Improve Vaccination Efficacy against the Filarial Nematode <i>Litomosoides sigmodontis</i> |
| title_fullStr | Potential of Nucleic Acid Receptor Ligands to Improve Vaccination Efficacy against the Filarial Nematode <i>Litomosoides sigmodontis</i> |
| title_full_unstemmed | Potential of Nucleic Acid Receptor Ligands to Improve Vaccination Efficacy against the Filarial Nematode <i>Litomosoides sigmodontis</i> |
| title_short | Potential of Nucleic Acid Receptor Ligands to Improve Vaccination Efficacy against the Filarial Nematode <i>Litomosoides sigmodontis</i> |
| title_sort | potential of nucleic acid receptor ligands to improve vaccination efficacy against the filarial nematode i litomosoides sigmodontis i |
| topic | filariae <i>Litomosoides sigmodontis</i> 3pRNA poly(I:C) vaccination nucleic acid receptor |
| url | https://www.mdpi.com/2076-393X/11/5/966 |
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