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 inVaccine Vol. 33; no. 36; pp. 4526 - 4532
Main Authors Sachan, Swati, Ramakrishnan, Saravanan, Annamalai, Arunsaravanakumar, Sharma, Bal Krishan, Malik, Hina, Saravanan, B.C, Jain, Lata, Saxena, Meeta, Kumar, Ajay, Krishnaswamy, Narayanan
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 26.08.2015
Elsevier Limited
Subjects
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
Newcastle disease
Immune response genes
Cytokines
TLR agonist
Resiquimod
Chicken
Adjuvant
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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.
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&lt;0.01). LTT stimulation index (P ≤ 0.01) as well as CD4(+) and CD8(+) cells in flow cytometry (P&lt;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&lt;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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Copyright © 2015 Elsevier Ltd. All rights reserved.
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IsPeerReviewed true
IsScholarly true
Issue 36
Keywords Newcastle disease
Immune response genes
Cytokines
TLR agonist
Resiquimod
Chicken
Adjuvant
Language English
License Copyright © 2015 Elsevier Ltd. All rights reserved.
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PublicationTitle Vaccine
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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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StartPage 4526
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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