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Nucleosomal Histone Proteins of L. donovani: A combination of recombinant H2A, H2B, H3 and H4 proteins were highly immunogenic and offered optimum prophylactic efficacy against Leishmania challenge in hamsters

หน่วยงาน Central Drug Research Institute (CDRI), India

รายละเอียด

ชื่อเรื่อง : Nucleosomal Histone Proteins of L. donovani: A combination of recombinant H2A, H2B, H3 and H4 proteins were highly immunogenic and offered optimum prophylactic efficacy against Leishmania challenge in hamsters
นักวิจัย : Baharia, R K , Tandon, Rati , Sahasrabuddhe, A A , Sundar, Shyam , Dube, Anuradha
คำค้น : Leishmania Donovani Nucleosomal Histone Proteins , Recombinant H2A , H2B , H3 And H4 , Immunogenicity , Prophylactic Efficacy , Hamsters
หน่วยงาน : Central Drug Research Institute (CDRI), India
ผู้ร่วมงาน : -
ปีพิมพ์ : 2557
อ้างอิง : PLoS One, 2014, 9(6): e97911 , http://hdl.handle.net/123456789/1371
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : CSIR-CDRI Communication No. 8675
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

The present study includes cloning and expression of recombinant L.donovani histone proteins (rLdH2B, rLdH3, rLdH2A and rLdH4), assessment of their immunogenicity in Leishmania infected cured patients/endemic contacts as well as in cured hamsters and finally evaluation of their prophylactic efficacy in hamsters against L. donovani challenge. All recombinant proteins were expressed and purified from the heterologous bacterial host system. Leishmania infected cured patients/ endemic contacts as well as cured hamsters exhibited significantly higher proliferative responses to individual recombinant histones and their pooled combination (rLdH2B+rLdH3+rLdH2A+rLdH4) than those of L.donovani infected hosts. The L.donovani soluble antigens (SLD) stimulated PBMCs of cured/exposed and Leishmania patients to produce a mixed Thl/Th2-type cytokine profile, whereas rLdH2B, rLdH3, rLdH2A, rLdH4 and pooled combination (rLdH2-4) stimulated the production of Th1 cytokines IFN-γ, IL-12 and TNF-α but not Th2 cytokines IL-4 or IL-10. The immunogenicity of these histone proteins along with their combination was also checked in cured hamsters where they stimulated higher lymphoproliferation and Nitric oxide production in lymphocytes of cured hamsters than that of infected controls. Moreover, significantly increased IgG2 response, an indicative of cell mediated immunity, was observed in cured hamsters against these individual proteins and their combination as compared to infected hamsters. Further, it was demonstrated that rLdH2B, rLdH3, rLdH2A and rLdH4 and pooled combination were able to provide considerable protection for hamsters against L. donovani challenge. The efficacy was supported by the increased iNOS mRNA transcripts and Th1-type cytokines - IFN-γ, IL-12 and TNF-α and down-regulation of IL-4, IL-10 and TGF-β. Hence, it is inferred that pooled rLdH2-4 elicits Thl-type of immune responses exclusively and confer considerable protection against experimental VL.

บรรณานุกรม :
Baharia, R K , Tandon, Rati , Sahasrabuddhe, A A , Sundar, Shyam , Dube, Anuradha . (2557). Nucleosomal Histone Proteins of L. donovani: A combination of recombinant H2A, H2B, H3 and H4 proteins were highly immunogenic and offered optimum prophylactic efficacy against Leishmania challenge in hamsters.
    : Central Drug Research Institute (CDRI), India.
Baharia, R K , Tandon, Rati , Sahasrabuddhe, A A , Sundar, Shyam , Dube, Anuradha . 2557. "Nucleosomal Histone Proteins of L. donovani: A combination of recombinant H2A, H2B, H3 and H4 proteins were highly immunogenic and offered optimum prophylactic efficacy against Leishmania challenge in hamsters".
    : Central Drug Research Institute (CDRI), India.
Baharia, R K , Tandon, Rati , Sahasrabuddhe, A A , Sundar, Shyam , Dube, Anuradha . "Nucleosomal Histone Proteins of L. donovani: A combination of recombinant H2A, H2B, H3 and H4 proteins were highly immunogenic and offered optimum prophylactic efficacy against Leishmania challenge in hamsters."
    : Central Drug Research Institute (CDRI), India, 2557. Print.
Baharia, R K , Tandon, Rati , Sahasrabuddhe, A A , Sundar, Shyam , Dube, Anuradha . Nucleosomal Histone Proteins of L. donovani: A combination of recombinant H2A, H2B, H3 and H4 proteins were highly immunogenic and offered optimum prophylactic efficacy against Leishmania challenge in hamsters. : Central Drug Research Institute (CDRI), India; 2557.