Sunflower seed oil combined with ginseng stem-leaf saponins as an adjuvant to enhance the immune response elicited by Newcastle disease vaccine in chickens.

The present study was to evaluate the adjuvant effect of sunflower seed oil containing saponins extracted from the stem and leaf of Panax ginseng C.A. Meyer (E515-D) on the immune response induced by an inactivated Newcastle disease virus (NDV) in chickens. The results showed that E515-D promoted significantly higher serum NDV-specific HI and neutralizing antibody responses, IFN-γ and IL-4 levels, and lymphocyte proliferative responses to Con A, LPS, and NDV antigen than the conventional adjuvant Marcol 52. Different adjuvant effect between E515-D and Marcol 52 may be attributed to different genes expressed in two groups. Transcriptome analysis of splenocytes showed that there were 1198 differentially expressed genes (DEGs) with 539 up and 659 down regulated in E515-D group while 1395 DEGs with 697 up and 698 down regulated in Marcol 52 group in comparison with the control group. Analysis of gene ontology (GO) term and kyoto encyclopedia of Genes and Genomes (KEGG) pathways showed that the predominant immune related pathways included "Toll-like receptor signaling pathway", "NOD-like receptor signaling pathway", "C-type lectin receptor signaling pathway", and "Phosphatidylinositol signaling system" in E515-D group while Marcol 52 were "NOD-like receptor signaling pathway", "Phagosome", and "Lysosome", and the most relevant DEGs in E515-D group were STAT1, STAT2, PI3K, and IL-6. Considering the excellent adjuvant activity and vegetable origin, E515-D deserves further study as an adjuvant for vaccines used in food animals.

[1]  Chilakamarti V. Ramana,et al.  Stat1-dependent and -independent pathways in IFN-γ-dependent signaling , 2002 .

[2]  Songhua Hu,et al.  Effect of oral administration of ginseng stem-and-leaf saponins (GSLS) on the immune responses to Newcastle disease vaccine in chickens. , 2011, Vaccine.

[3]  K. Tomii,et al.  Evolutionary analyses of caspase-8 and its paralogs: Deep origins of the apoptotic signaling pathways. , 2015, BioEssays : news and reviews in molecular, cellular and developmental biology.

[4]  W. Zhe Studies on the relationship of challenge against newcastle disease and serology(HI) test , 2004 .

[5]  M. Rothschild,et al.  RNA-seq analysis of broiler liver transcriptome reveals novel responses to high ambient temperature , 2014, BMC Genomics.

[6]  D. Kapczynski,et al.  Maternal antibody inhibition of recombinant Newcastle disease virus vectored vaccine in a primary or booster avian influenza vaccination program of broiler chickens. , 2018, Vaccine.

[7]  Feifei Guo,et al.  Screening and identification of critical transcription factors involved in the protection of cardiomyocytes against hydrogen peroxide-induced damage by Yixin-shu , 2017, Scientific Reports.

[8]  Songhua Hu,et al.  Ginsenosides Rg1 and Re act as adjuvant via TLR4 signaling pathway. , 2012, Vaccine.

[9]  C. Afonso,et al.  Newcastle disease vaccines—A solved problem or a continuous challenge? , 2016, Veterinary Microbiology.

[10]  Siguo Liu,et al.  A bacterial ghost improves the immunological efficacy of a Newcastle disease virus inactivated vaccine. , 2017, Veterinary microbiology.

[11]  H. Stone Efficacy of experimental animal and vegetable oil-emulsion vaccines for Newcastle disease and avian influenza. , 1993, Avian diseases.

[12]  Huahua Yu,et al.  Chitosan, hydroxypropyltrimethyl ammonium chloride chitosan and sulfated chitosan nanoparticles as adjuvants for inactivated Newcastle disease vaccine. , 2020, Carbohydrate polymers.

[13]  M. Yamanaka,et al.  Local pathological reactions and immune response of chickens to ISA-70 and other adjuvants containing Newcastle disease virus antigen. , 1993, Avian diseases.

[14]  S. Gringhuis,et al.  Signalling through C-type lectin receptors: shaping immune responses , 2009, Nature Reviews Immunology.

[15]  T. Qin,et al.  Cordyceps militaris polysaccharides can improve the immune efficacy of Newcastle disease vaccine in chicken. , 2013, International journal of biological macromolecules.

[16]  S. Rhee,et al.  Toll-like Receptors 2 and 4 Activate STAT1 Serine Phosphorylation by Distinct Mechanisms in Macrophages* , 2003, Journal of Biological Chemistry.

[17]  S. Akira,et al.  Pathogen Recognition and Innate Immunity , 2006, Cell.

[18]  H. Stone Newcastle disease oil emulsion vaccines prepared with animal, vegetable, and synthetic oils. , 1997, Avian diseases.

[19]  D. Kapczynski,et al.  Immune responses of poultry to Newcastle disease virus. , 2013, Developmental and comparative immunology.

[20]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[21]  X. Chi,et al.  Ginsenoside Rg1 enhanced immune responses to infectious bursal disease vaccine in chickens with oxidative stress induced by cyclophosphamide , 2018, Poultry science.

[22]  E. Claassen,et al.  Immune responses and side effects of five different oil-based adjuvants in mice. , 1998, Veterinary immunology and immunopathology.

[23]  Niwat Chansiripornchai,et al.  Efficacy of live B1 or Ulster 2C Newcastle disease vaccines simultaneously vaccinated with inactivated oil adjuvant vaccine for protection of Newcastle disease virus in broiler chickens , 2006, Acta veterinaria Scandinavica.

[24]  C. Afonso,et al.  Characterization of Live LaSota Vaccine Strain–Induced Protection in Chickens upon Early Challenge with a Virulent Newcastle Disease Virus of Heterologous Genotype , 2012, Avian diseases.

[25]  B. Pulendran,et al.  Modulation of adaptive immunity with Toll-like receptors. , 2009, Seminars in immunology.

[26]  Dongxiao Sun,et al.  Using RNA sequencing to identify putative competing endogenous RNAs (ceRNAs) potentially regulating fat metabolism in bovine liver , 2017, Scientific Reports.

[27]  G. Koch,et al.  Immunoglobulin Class Distribution of Systemic and Mucosal Antibody Responses to Newcastle Disease in Chickens , 2003, Avian diseases.

[28]  Xiaohua Wang,et al.  Response of live Newcastle disease virus encapsulated in N-2-hydroxypropyl dimethylethyl ammonium chloride chitosan nanoparticles. , 2017, Carbohydrate polymers.

[29]  W. Wang,et al.  Enhancement of humoral immune responses to inactivated Newcastle disease and avian influenza vaccines by oral administration of ginseng stem-and-leaf saponins in chickens. , 2011, Poultry science.

[30]  Z. Bu,et al.  Novel in-ovo chimeric recombinant Newcastle disease vaccine protects against both Newcastle disease and infectious bursal disease. , 2014, Vaccine.

[31]  W. Xu,et al.  Transcriptome analysis of bovine lymphocytes stimulated by Atractylodis macrocephalae Koidz. polysaccharides in vitro. , 2018, Veterinary immunology and immunopathology.

[32]  X. Chi,et al.  Combined adjuvant effect of ginseng stem-leaf saponins and selenium on immune responses to a live bivalent vaccine of Newcastle disease virus and infectious bronchitis virus in chickens , 2019, Poultry science.

[33]  P. Petronini,et al.  Targeting PI3K/AKT/mTOR pathway in non small cell lung cancer. , 2014, Biochemical pharmacology.

[34]  S. Hu,et al.  Improved immune responses to a bivalent vaccine of Newcastle disease and avian influenza in chickens by ginseng stem-leaf saponins. , 2015, Veterinary immunology and immunopathology.

[35]  J. Prieto,et al.  Hepatitis C virus induces the expression of CCL17 and CCL22 chemokines that attract regulatory T cells to the site of infection. , 2011, Journal of hepatology.

[36]  H. Pan,et al.  Ginsenoside Rg1 regulates innate immune responses in macrophages through differentially modulating the NF-κB and PI3K/Akt/mTOR pathways. , 2014, International immunopharmacology.

[37]  W. Xu,et al.  Soybean oil containing ginseng saponins as adjuvants promotes production of cytokines and enhances immune responses to foot‐and‐mouth disease vaccine , 2018, Microbiology and immunology.

[38]  D. Levy,et al.  JAK-STAT Signaling: From Interferons to Cytokines* , 2007, Journal of Biological Chemistry.

[39]  Hua Yu,et al.  STATs in cancer inflammation and immunity: a leading role for STAT3 , 2009, Nature Reviews Cancer.

[40]  Songhua Hu,et al.  Rapeseed Oil and Ginseng Saponins Work Synergistically To Enhance Th1 and Th2 Immune Responses Induced by the Foot-and-Mouth Disease Vaccine , 2014, Clinical and Vaccine Immunology.

[41]  Zhenhuan Guo,et al.  Epimedium polysaccharide and propolis flavone can synergistically stimulate lymphocyte proliferation in vitro and enhance the immune responses to ND vaccine in chickens. , 2010, International journal of biological macromolecules.

[42]  S. Fukanoki,et al.  Effect of liquid paraffin on antibody responses and local adverse reactions of bivalent oil adjuvanted vaccines containing newcastle disease virus and infectious bronchitis virus. , 2000, The Journal of veterinary medical science.

[43]  M. Megahed,et al.  GENETIC CHARACTERIZATION OF EGYPTIAN NEWCASTLE DISEASE VIRUS STRAINS ISOLATED FROM FLOCKS VACCINATED AGAINST NEWCASTLE DISEASE VIRUS, 2014-2015 , 2018 .

[44]  Rachael P. Huntley,et al.  Gene Ontology annotation of sequence-specific DNA binding transcription factors: setting the stage for a large-scale curation effort , 2013, Database J. Biol. Databases Curation.

[45]  Xinglong Wang,et al.  Adenoviral‐expressed recombinant granulocyte monocyte colony‐stimulating factor (GM‐CSF) enhances protective immunity induced by inactivated Newcastle Disease Virus (NDV) vaccine , 2017, Antiviral research.

[46]  W. Xu,et al.  Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant , 2019, Vaccines.

[47]  Songhua Hu,et al.  Ginseng Stem-Leaf Saponins and Oil Adjuvant Synergistically Promote the Immune Responses to Newcastle Disease in Chickens , 2012 .

[48]  E. Elinav,et al.  Integration of Innate Immune Signaling. , 2016, Trends in immunology.