Adjuvant potential of resiquimod with inactivated Newcastle disease vaccine and its mechanism of action in chicken
Highlights • Resiquimod (R-848) showed potential adjuvant capacity with Newcastle disease (ND) vaccine in SPF chicken. • R-848 enhanced antigen specific humoral as well as cellular immune responses. • R-848 up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-4, IL-1β, MHC-II and iNOS transcripts...
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Published in | Vaccine Vol. 33; no. 36; pp. 4526 - 4532 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
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26.08.2015
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Abstract | Highlights • Resiquimod (R-848) showed potential adjuvant capacity with Newcastle disease (ND) vaccine in SPF chicken. • R-848 enhanced antigen specific humoral as well as cellular immune responses. • R-848 up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-4, IL-1β, MHC-II and iNOS transcripts in the chicken spleen. • R-848 potentiated the protection capacity of inactivated ND vaccine against virulent ND virus challenge. |
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AbstractList | Resiquimod (R-848), an imidazoquinoline compound, is a potent synthetic Toll-like receptor (TLR) 7 agonist. Although the solitary adjuvant potential of R-848 is well established in mammals, such reports are not available in avian species hitherto. Hence, the adjuvant potential of R-848 was tested in SPF chicken in this study. Two week old chicks were divided into four groups (10 birds/group) viz., control (A), inactivated Newcastle disease virus (NDV) vaccine prepared from velogenic strain (B), commercial oil adjuvanted inactivated NDV vaccine prepared from lentogenic strain (C) and inactivated NDV vaccine prepared from velogenic strain with R-848 (D). Booster was given two weeks post primary vaccination. Humoral immune response was assessed by haemagglutination inhibition (HI) test and ELISA while the cellular immune response was quantified by lymphocyte transformation test (LTT) and flow cytometry post-vaccination. Entire experiment was repeated twice to check the reproducibility. Highest HI titre was observed in group D at post booster weeks 1 and 2 that corresponds to mean log2 HI titre of 6.4 ± 0.16 and 6.8 ± 0.13, respectively. The response was significantly higher than that of group B or C (P<0.01). LTT stimulation index (P ≤ 0.01) as well as CD4(+) and CD8(+) cells in flow cytometry (P<0.05) were significantly high and maximum in group D. Group D conferred complete protection against virulent NDV challenge, while it was only 80% in group B and C. To understand the effects of R-848, the kinetics of immune response genes in spleen were analyzed using quantitative real-time PCR after R-848 administration (50 μg/bird, i.m. route). Resiquimod significantly up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-1β, IL-4, iNOS and MHC-II genes (P<0.01). In conclusion, the study demonstrated the adjuvant potential of R-848 when co-administered with inactivated NDV vaccine in SPF chicken which is likely due to the up-regulation of immune response genes. Resiquimod (R-848), an imidazoquinoline compound, is a potent synthetic Toll-like receptor (TLR) 7 agonist. Although the solitary adjuvant potential of R-848 is well established in mammals, such reports are not available in avian species hitherto. Hence, the adjuvant potential of R-848 was tested in SPF chicken in this study. Two week old chicks were divided into four groups (10birds/group) viz., control (A), inactivated Newcastle disease virus (NDV) vaccine prepared from velogenic strain (B), commercial oil adjuvanted inactivated NDV vaccine prepared from lentogenic strain (C) and inactivated NDV vaccine prepared from velogenic strain with R-848 (D). Booster was given two weeks post primary vaccination. Humoral immune response was assessed by haemagglutination inhibition (HI) test and ELISA while the cellular immune response was quantified by lymphocyte transformation test (LTT) and flow cytometry post-vaccination. Entire experiment was repeated twice to check the reproducibility. Highest HI titre was observed in group D at post booster weeks 1 and 2 that corresponds to mean log2 HI titre of 6.4 plus or minus 0.16 and 6.8 plus or minus 0.13, respectively. The response was significantly higher than that of group B or C (P<0.01). LTT stimulation index (P less than or equal to 0.01) as well as CD4+ and CD8+ cells in flow cytometry (P<0.05) were significantly high and maximum in group D. Group D conferred complete protection against virulent NDV challenge, while it was only 80% in group B and C. To understand the effects of R-848, the kinetics of immune response genes in spleen were analyzed using quantitative real-time PCR after R-848 administration (50 mu g/bird, i.m. route). Resiquimod significantly up-regulated the expression of IFN- alpha , IFN- beta , IFN- gamma , IL-1 beta , IL-4, iNOS and MHC-II genes (P<0.01). In conclusion, the study demonstrated the adjuvant potential of R-848 when co-administered with inactivated NDV vaccine in SPF chicken which is likely due to the up-regulation of immune response genes. Resiquimod (R-848), an imidazoquinoline compound, is a potent synthetic Toll-like receptor (TLR) 7 agonist. Although the solitary adjuvant potential of R-848 is well established in mammals, such reports are not available in avian specieshitherto. Hence, the adjuvant potential of R-848 was tested in SPF chicken in this study. Two week old chicks were divided into four groups (10birds/group)viz., control (A), inactivated Newcastle disease virus (NDV) vaccine prepared from velogenic strain (B), commercial oil adjuvanted inactivated NDV vaccine prepared from lentogenic strain (C) and inactivated NDV vaccine prepared from velogenic strain with R-848 (D). Booster was given two weeks post primary vaccination. Humoral immune response was assessed by haemagglutination inhibition (HI) test and ELISA while the cellular immune response was quantified by lymphocyte transformation test (LTT) and flow cytometry post-vaccination. Entire experiment was repeated twice to check the reproducibility. Highest HI titre was observed in group D at post booster weeks 1 and 2 that corresponds to mean log2HI titre of 6.4±0.16 and 6.8±0.13, respectively. The response was significantly higher than that of group B or C (P<0.01). LTT stimulation index (P<=0.01) as well as CD4+and CD8+cells in flow cytometry (P<0.05) were significantly high and maximum in group D. Group D conferred complete protection against virulent NDV challenge, while it was only 80% in group B and C. To understand the effects of R-848, the kinetics of immune response genes in spleen were analyzed using quantitative real-time PCR after R-848 administration (50μg/bird, i.m. route). Resiquimod significantly up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-1β, IL-4, iNOS and MHC-II genes (P<0.01). In conclusion, the study demonstrated the adjuvant potential of R-848 when co-administered with inactivated NDV vaccine in SPF chicken which is likely due to the up-regulation of immune response genes. •Resiquimod (R-848) showed potential adjuvant capacity with Newcastle disease (ND) vaccine in SPF chicken.•R-848 enhanced antigen specific humoral as well as cellular immune responses.•R-848 up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-4, IL-1β, MHC-II and iNOS transcripts in the chicken spleen.•R-848 potentiated the protection capacity of inactivated ND vaccine against virulent ND virus challenge. Resiquimod (R-848), an imidazoquinoline compound, is a potent synthetic Toll-like receptor (TLR) 7 agonist. Although the solitary adjuvant potential of R-848 is well established in mammals, such reports are not available in avian species hitherto. Hence, the adjuvant potential of R-848 was tested in SPF chicken in this study. Two week old chicks were divided into four groups (10birds/group) viz., control (A), inactivated Newcastle disease virus (NDV) vaccine prepared from velogenic strain (B), commercial oil adjuvanted inactivated NDV vaccine prepared from lentogenic strain (C) and inactivated NDV vaccine prepared from velogenic strain with R-848 (D). Booster was given two weeks post primary vaccination. Humoral immune response was assessed by haemagglutination inhibition (HI) test and ELISA while the cellular immune response was quantified by lymphocyte transformation test (LTT) and flow cytometry post-vaccination. Entire experiment was repeated twice to check the reproducibility. Highest HI titre was observed in group D at post booster weeks 1 and 2 that corresponds to mean log2 HI titre of 6.4±0.16 and 6.8±0.13, respectively. The response was significantly higher than that of group B or C (P<0.01). LTT stimulation index (P≤0.01) as well as CD4+ and CD8+ cells in flow cytometry (P<0.05) were significantly high and maximum in group D. Group D conferred complete protection against virulent NDV challenge, while it was only 80% in group B and C. To understand the effects of R-848, the kinetics of immune response genes in spleen were analyzed using quantitative real-time PCR after R-848 administration (50μg/bird, i.m. route). Resiquimod significantly up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-1β, IL-4, iNOS and MHC-II genes (P<0.01). In conclusion, the study demonstrated the adjuvant potential of R-848 when co-administered with inactivated NDV vaccine in SPF chicken which is likely due to the up-regulation of immune response genes. Resiquimod (R-848), an imidazoquinoline compound, is a potent synthetic Toll-like receptor (TLR) 7 agonist. Although the solitary adjuvant potential of R-848 is well established in mammals, such reports are not available in avian species hitherto. Hence, the adjuvant potential of R-848 was tested in SPF chicken in this study. Two week old chicks were divided into four groups (10 birds/group) viz., control (A), inactivated Newcastle disease virus (NDV) vaccine prepared from velogenic strain (B), commercial oil adjuvanted inactivated NDV vaccine prepared from lentogenic strain (C) and inactivated NDV vaccine prepared from velogenic strain with R-848 (D). Booster was given two weeks post primary vaccination. Humoral immune response was assessed by haemagglutination inhibition (HI) test and ELISA while the cellular immune response was quantified by lymphocyte transformation test (LTT) and flow cytometry post-vaccination. Entire experiment was repeated twice to check the reproducibility. Highest HI titre was observed in group D at post booster weeks 1 and 2 that corresponds to mean log2 HI titre of 6.4 ± 0.16 and 6.8 ± 0.13, respectively. The response was significantly higher than that of group B or C (P<0.01). LTT stimulation index (P ≤ 0.01) as well as CD4(+) and CD8(+) cells in flow cytometry (P<0.05) were significantly high and maximum in group D. Group D conferred complete protection against virulent NDV challenge, while it was only 80% in group B and C. To understand the effects of R-848, the kinetics of immune response genes in spleen were analyzed using quantitative real-time PCR after R-848 administration (50 μg/bird, i.m. route). Resiquimod significantly up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-1β, IL-4, iNOS and MHC-II genes (P<0.01). In conclusion, the study demonstrated the adjuvant potential of R-848 when co-administered with inactivated NDV vaccine in SPF chicken which is likely due to the up-regulation of immune response genes. Highlights • Resiquimod (R-848) showed potential adjuvant capacity with Newcastle disease (ND) vaccine in SPF chicken. • R-848 enhanced antigen specific humoral as well as cellular immune responses. • R-848 up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-4, IL-1β, MHC-II and iNOS transcripts in the chicken spleen. • R-848 potentiated the protection capacity of inactivated ND vaccine against virulent ND virus challenge. |
Author | Saxena, Meeta Annamalai, Arunsaravanakumar Saravanan, B.C Sachan, Swati Sharma, Bal Krishan Krishnaswamy, Narayanan Ramakrishnan, Saravanan Kumar, Ajay Malik, Hina Jain, Lata |
Author_xml | – sequence: 1 fullname: Sachan, Swati – sequence: 2 fullname: Ramakrishnan, Saravanan – sequence: 3 fullname: Annamalai, Arunsaravanakumar – sequence: 4 fullname: Sharma, Bal Krishan – sequence: 5 fullname: Malik, Hina – sequence: 6 fullname: Saravanan, B.C – sequence: 7 fullname: Jain, Lata – sequence: 8 fullname: Saxena, Meeta – sequence: 9 fullname: Kumar, Ajay – sequence: 10 fullname: Krishnaswamy, Narayanan |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26192354$$D View this record in MEDLINE/PubMed |
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Keywords | Newcastle disease Immune response genes Cytokines TLR agonist Resiquimod Chicken Adjuvant |
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fullname: Vasilakos |
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Snippet | Highlights • Resiquimod (R-848) showed potential adjuvant capacity with Newcastle disease (ND) vaccine in SPF chicken. • R-848 enhanced antigen specific... •Resiquimod (R-848) showed potential adjuvant capacity with Newcastle disease (ND) vaccine in SPF chicken.•R-848 enhanced antigen specific humoral as well as... Resiquimod (R-848), an imidazoquinoline compound, is a potent synthetic Toll-like receptor (TLR) 7 agonist. Although the solitary adjuvant potential of R-848... |
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SubjectTerms | Adjuvant Adjuvants, Immunologic - administration & dosage Allergy and Immunology Animal vaccines Animals Antibodies, Viral - blood Birds Chicken Chickens Cytokines Enzyme-Linked Immunosorbent Assay Flow Cytometry Gene Expression Profiling Genes Hemagglutination Inhibition Tests Imidazoles - administration & dosage Immune response Immune response genes Lymphocytes Lymphocytes - immunology Newcastle disease Newcastle Disease - prevention & control Newcastle disease virus Poultry Resiquimod TLR agonist Vaccines Vaccines, Inactivated - administration & dosage Viral Vaccines - administration & dosage |
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Title | Adjuvant potential of resiquimod with inactivated Newcastle disease vaccine and its mechanism of action in chicken |
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