BECC438b TLR4 agonist supports unique immune response profiles from nasal and muscular DTaP pertussis vaccines in murine challenge models
The protection afforded by acellular pertussis vaccines wanes over time, and there is a need to develop improved vaccine formulations. Options to improve the vaccines involve the utilization of different adjuvants and administration via different routes. While intramuscular (IM) vaccination provides a robust systemic immune response, intranasal (IN) vaccination theoretically induces a localized immune response within the nasal cavity. In the case of a Bordetella pertussis infection, IN vaccination results in an immune response that is similar to natural infection, which provides the longest duration of protection. Current acellular formulations utilize an alum adjuvant, and antibody levels wane over time. To overcome the current limitations with the acellular vaccine, we incorporated a novel TLR4 agonist, BECC438b, into both IM and IN acellular formulations to determine its ability to protect against infection in a murine airway challenge model. Following immunization and challenge, we observed that DTaP + BECC438b reduced bacterial burden within the lung and trachea for both administration routes when compared with mock-vaccinated and challenged (MVC) mice. Interestingly, IN administration of DTaP + BECC438b induced a Th1-polarized immune response, while IM vaccination polarized toward a Th2 immune response. RNA sequencing analysis of the lung demonstrated that DTaP + BECC438b activates biological pathways similar to natural infection. Additionally, IN administration of DTaP + BECC438b activated the expression of genes involved in a multitude of pathways associated with the immune system. Overall, these data suggest that BECC438b adjuvant and the IN vaccination route can impact efficacy and responses of pertussis vaccines in pre-clinical mouse models.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:92 |
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| Enthalten in: |
Infection and immunity - 92(2024), 3 vom: 12. März, Seite e0022323 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
DeJong, Megan A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.03.2024 Date Revised 14.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1128/iai.00223-23 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368130134 |
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| 100 | 1 | |a DeJong, Megan A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a BECC438b TLR4 agonist supports unique immune response profiles from nasal and muscular DTaP pertussis vaccines in murine challenge models |
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| 500 | |a Date Completed 13.03.2024 | ||
| 500 | |a Date Revised 14.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The protection afforded by acellular pertussis vaccines wanes over time, and there is a need to develop improved vaccine formulations. Options to improve the vaccines involve the utilization of different adjuvants and administration via different routes. While intramuscular (IM) vaccination provides a robust systemic immune response, intranasal (IN) vaccination theoretically induces a localized immune response within the nasal cavity. In the case of a Bordetella pertussis infection, IN vaccination results in an immune response that is similar to natural infection, which provides the longest duration of protection. Current acellular formulations utilize an alum adjuvant, and antibody levels wane over time. To overcome the current limitations with the acellular vaccine, we incorporated a novel TLR4 agonist, BECC438b, into both IM and IN acellular formulations to determine its ability to protect against infection in a murine airway challenge model. Following immunization and challenge, we observed that DTaP + BECC438b reduced bacterial burden within the lung and trachea for both administration routes when compared with mock-vaccinated and challenged (MVC) mice. Interestingly, IN administration of DTaP + BECC438b induced a Th1-polarized immune response, while IM vaccination polarized toward a Th2 immune response. RNA sequencing analysis of the lung demonstrated that DTaP + BECC438b activates biological pathways similar to natural infection. Additionally, IN administration of DTaP + BECC438b activated the expression of genes involved in a multitude of pathways associated with the immune system. Overall, these data suggest that BECC438b adjuvant and the IN vaccination route can impact efficacy and responses of pertussis vaccines in pre-clinical mouse models | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BECC | |
| 650 | 4 | |a Bordetella pertussis | |
| 650 | 4 | |a DTaP | |
| 650 | 4 | |a FHA | |
| 650 | 4 | |a TLR4 agonist | |
| 650 | 4 | |a adjuvant | |
| 650 | 4 | |a bacterial challenge | |
| 650 | 4 | |a leukocytosis | |
| 650 | 4 | |a lipid A | |
| 650 | 4 | |a pertussis | |
| 650 | 4 | |a pertussis mouse model | |
| 650 | 4 | |a pertussis toxin | |
| 650 | 4 | |a pertussis toxoid | |
| 650 | 4 | |a vaccine evaluation | |
| 650 | 4 | |a vaccines | |
| 650 | 4 | |a whooping cough | |
| 650 | 7 | |a Diphtheria-Tetanus-acellular Pertussis Vaccines |2 NLM | |
| 650 | 7 | |a Toll-Like Receptor 4 |2 NLM | |
| 650 | 7 | |a Pertussis Vaccine |2 NLM | |
| 650 | 7 | |a Diphtheria-Tetanus-Pertussis Vaccine |2 NLM | |
| 650 | 7 | |a Adjuvants, Immunologic |2 NLM | |
| 650 | 7 | |a Antibodies, Bacterial |2 NLM | |
| 700 | 1 | |a Wolf, M Allison |e verfasserin |4 aut | |
| 700 | 1 | |a Bitzer, Graham J |e verfasserin |4 aut | |
| 700 | 1 | |a Hall, Jesse M |e verfasserin |4 aut | |
| 700 | 1 | |a Fitzgerald, Nicholas A |e verfasserin |4 aut | |
| 700 | 1 | |a Pyles, Gage M |e verfasserin |4 aut | |
| 700 | 1 | |a Huckaby, Annalisa B |e verfasserin |4 aut | |
| 700 | 1 | |a Petty, Jonathan E |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Katherine |e verfasserin |4 aut | |
| 700 | 1 | |a Barbier, Mariette |e verfasserin |4 aut | |
| 700 | 1 | |a Bevere, Justin R |e verfasserin |4 aut | |
| 700 | 1 | |a Ernst, Robert K |e verfasserin |4 aut | |
| 700 | 1 | |a Damron, F Heath |e verfasserin |4 aut | |
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