The Adjuvants Polyphosphazene (PCEP) and a Combination of Curdlan Plus Leptin Promote a Th17-Type Immune Response to an Intramuscular Vaccine in Mice
Our aim was to determine whether polyphosphazene (PCEP), Curdlan (β-glucan, a dectin-1 agonist), and Leptin could act as adjuvants to promote a Th17-type adaptive immune response in mice. Mice were vaccinated via the intramuscular route then boosted three weeks later with Ovalbumin plus: PCEP, Lepti...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/5/507 |
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| author | Alyssa Chaffey Glenn Hamonic Dylan Chand George K. Mutwiri Heather L. Wilson |
| author_facet | Alyssa Chaffey Glenn Hamonic Dylan Chand George K. Mutwiri Heather L. Wilson |
| author_sort | Alyssa Chaffey |
| collection | DOAJ |
| description | Our aim was to determine whether polyphosphazene (PCEP), Curdlan (β-glucan, a dectin-1 agonist), and Leptin could act as adjuvants to promote a Th17-type adaptive immune response in mice. Mice were vaccinated via the intramuscular route then boosted three weeks later with Ovalbumin plus: PCEP, Leptin, Curdlan, PCEP+Curdlan, Curdlan+Leptin, or saline. Mice vaccinated with OVA+PCEP and OVA+Curdlan+Leptin showed significantly higher frequency of antigen-specific CD4+ T cells secreting IL-17 relative to OVA-vaccinated mice. No formulation increased the frequency of CD4+ T cells secreting IL-4 or IFNγ. Since activation of innate immunity precedes the development of adaptive immunity, we wished to establish whether induction of Th17-type immunity could be predicted from in vitro experiments and/or from the local cytokine environment after immunization with adjuvants alone. Elevated IL-6 and TGFβ with reduced secretion of IL-12 is a cytokine milieu known to promote differentiation of Th17-type immunity. We injected the immunostimulants or saline buffer into murine thigh muscles and measured acute local cytokine production. PCEP induced significant production of IL-6 and reduced IL-12 production in muscle but it did not lead to elevated TGFβ production. Curdlan+Leptin injected into muscle induced significant production of TGFβ and IL-17 but not IL-6 or IL-12. We also stimulated splenocytes with media or PCEP, Leptin, Curdlan, PCEP+Curdlan, Curdlan+Leptin, PCEP+Leptin, and PCEP+Curdlan+Leptin and measured cytokine production. PCEP stimulation of splenocytes failed to induce significant production of IL-6, IL-12, TGFβ, or IL-17 and therefore ex vivo splenocyte stimulation failed to predict the increased frequency of Th17-type T cells in response to the vaccine. Curdlan-stimulated splenocytes produced Th1-type, inducing cytokine, IL-12. Curdlan+/-PCEP stimulated TGF-β production and Curdlan+Leptin+/- PCEP induced secretion of IL-17. We conclude that PCEP as well as Curdlan+Leptin are Th17-type vaccine adjuvants in mice but that cytokines produced in response to these adjuvants in muscle after injection or in ex vivo cultured splenocytes did not predict their role as a Th17-type adjuvant. Together, these data suggest that the cytokine environments induced by these immunostimulants did not predict induction of an antigen-specific Th17-type adaptive immune response. This is the first report of these adjuvants inducing a Th17-type adaptive immune response. |
| first_indexed | 2024-03-10T11:25:02Z |
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| id | doaj.art-9cc6ae4800c54dbeaff56280ecadf11f |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T11:25:02Z |
| publishDate | 2021-05-01 |
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| spelling | doaj.art-9cc6ae4800c54dbeaff56280ecadf11f2023-11-21T19:45:54ZengMDPI AGVaccines2076-393X2021-05-019550710.3390/vaccines9050507The Adjuvants Polyphosphazene (PCEP) and a Combination of Curdlan Plus Leptin Promote a Th17-Type Immune Response to an Intramuscular Vaccine in MiceAlyssa Chaffey0Glenn Hamonic1Dylan Chand2George K. Mutwiri3Heather L. Wilson4Vaccinology & Immunotherapeutic Program, School of Public Health, University of Saskatchewan, 104 Clinic Place, Saskatoon, SK S7N 2Z4, CanadaLarge Animal Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, CanadaVaccinology & Immunotherapeutic Program, School of Public Health, University of Saskatchewan, 104 Clinic Place, Saskatoon, SK S7N 2Z4, CanadaVaccinology & Immunotherapeutic Program, School of Public Health, University of Saskatchewan, 104 Clinic Place, Saskatoon, SK S7N 2Z4, CanadaVaccinology & Immunotherapeutic Program, School of Public Health, University of Saskatchewan, 104 Clinic Place, Saskatoon, SK S7N 2Z4, CanadaOur aim was to determine whether polyphosphazene (PCEP), Curdlan (β-glucan, a dectin-1 agonist), and Leptin could act as adjuvants to promote a Th17-type adaptive immune response in mice. Mice were vaccinated via the intramuscular route then boosted three weeks later with Ovalbumin plus: PCEP, Leptin, Curdlan, PCEP+Curdlan, Curdlan+Leptin, or saline. Mice vaccinated with OVA+PCEP and OVA+Curdlan+Leptin showed significantly higher frequency of antigen-specific CD4+ T cells secreting IL-17 relative to OVA-vaccinated mice. No formulation increased the frequency of CD4+ T cells secreting IL-4 or IFNγ. Since activation of innate immunity precedes the development of adaptive immunity, we wished to establish whether induction of Th17-type immunity could be predicted from in vitro experiments and/or from the local cytokine environment after immunization with adjuvants alone. Elevated IL-6 and TGFβ with reduced secretion of IL-12 is a cytokine milieu known to promote differentiation of Th17-type immunity. We injected the immunostimulants or saline buffer into murine thigh muscles and measured acute local cytokine production. PCEP induced significant production of IL-6 and reduced IL-12 production in muscle but it did not lead to elevated TGFβ production. Curdlan+Leptin injected into muscle induced significant production of TGFβ and IL-17 but not IL-6 or IL-12. We also stimulated splenocytes with media or PCEP, Leptin, Curdlan, PCEP+Curdlan, Curdlan+Leptin, PCEP+Leptin, and PCEP+Curdlan+Leptin and measured cytokine production. PCEP stimulation of splenocytes failed to induce significant production of IL-6, IL-12, TGFβ, or IL-17 and therefore ex vivo splenocyte stimulation failed to predict the increased frequency of Th17-type T cells in response to the vaccine. Curdlan-stimulated splenocytes produced Th1-type, inducing cytokine, IL-12. Curdlan+/-PCEP stimulated TGF-β production and Curdlan+Leptin+/- PCEP induced secretion of IL-17. We conclude that PCEP as well as Curdlan+Leptin are Th17-type vaccine adjuvants in mice but that cytokines produced in response to these adjuvants in muscle after injection or in ex vivo cultured splenocytes did not predict their role as a Th17-type adjuvant. Together, these data suggest that the cytokine environments induced by these immunostimulants did not predict induction of an antigen-specific Th17-type adaptive immune response. This is the first report of these adjuvants inducing a Th17-type adaptive immune response.https://www.mdpi.com/2076-393X/9/5/507miceovalbumincell-mediated immunityflow cytometryinterleukin-17Th17-type T cells |
| spellingShingle | Alyssa Chaffey Glenn Hamonic Dylan Chand George K. Mutwiri Heather L. Wilson The Adjuvants Polyphosphazene (PCEP) and a Combination of Curdlan Plus Leptin Promote a Th17-Type Immune Response to an Intramuscular Vaccine in Mice Vaccines mice ovalbumin cell-mediated immunity flow cytometry interleukin-17 Th17-type T cells |
| title | The Adjuvants Polyphosphazene (PCEP) and a Combination of Curdlan Plus Leptin Promote a Th17-Type Immune Response to an Intramuscular Vaccine in Mice |
| title_full | The Adjuvants Polyphosphazene (PCEP) and a Combination of Curdlan Plus Leptin Promote a Th17-Type Immune Response to an Intramuscular Vaccine in Mice |
| title_fullStr | The Adjuvants Polyphosphazene (PCEP) and a Combination of Curdlan Plus Leptin Promote a Th17-Type Immune Response to an Intramuscular Vaccine in Mice |
| title_full_unstemmed | The Adjuvants Polyphosphazene (PCEP) and a Combination of Curdlan Plus Leptin Promote a Th17-Type Immune Response to an Intramuscular Vaccine in Mice |
| title_short | The Adjuvants Polyphosphazene (PCEP) and a Combination of Curdlan Plus Leptin Promote a Th17-Type Immune Response to an Intramuscular Vaccine in Mice |
| title_sort | adjuvants polyphosphazene pcep and a combination of curdlan plus leptin promote a th17 type immune response to an intramuscular vaccine in mice |
| topic | mice ovalbumin cell-mediated immunity flow cytometry interleukin-17 Th17-type T cells |
| url | https://www.mdpi.com/2076-393X/9/5/507 |
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