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Recombinant Bivalent Fusion Protein rVE Induces CD4+ and CD8+ T-Cell Mediated Memory Immune Response for Protection Against Yersinia enterocolitica Infection

Please always quote using this URN: urn:nbn:de:bvb:20-opus-136114
  • Studies investigating the correlates of immune protection against Yersinia infection have established that both humoral and cell mediated immune responses are required for the comprehensive protection. In our previous study, we established that the bivalent fusion protein (rVE) comprising immunologically active regions of Y pestis LcrV (100-270 aa) and YopE (50-213 aa) proteins conferred complete passive and active protection against lethal Y enterocolitica 8081 challenge. In the present study, cohort of BALB/c mice immunized with rVE or itsStudies investigating the correlates of immune protection against Yersinia infection have established that both humoral and cell mediated immune responses are required for the comprehensive protection. In our previous study, we established that the bivalent fusion protein (rVE) comprising immunologically active regions of Y pestis LcrV (100-270 aa) and YopE (50-213 aa) proteins conferred complete passive and active protection against lethal Y enterocolitica 8081 challenge. In the present study, cohort of BALB/c mice immunized with rVE or its component proteins rV, rE were assessed for cell mediated immune responses and memory immune protection against Y enterocolitica 8081 rVE immunization resulted in extensive proliferation of both CD4 and CD8 T cell subsets; significantly high antibody titer with balanced IgG1: IgG2a/IgG2b isotypes (1:1 ratio) and up regulation of both Th1 (INF-\(\alpha\), IFN-\(\gamma\), IL 2, and IL 12) and Th2 (IL 4) cytokines. On the other hand, rV immunization resulted in Th2 biased IgG response (11:1 ratio) and proliferation of CD4+ T-cell; rE group of mice exhibited considerably lower serum antibody titer with predominant Th1 response (1:3 ratio) and CD8+ T-cell proliferation. Comprehensive protection with superior survival (100%) was observed among rVE immunized mice when compared to the significantly lower survival rates among rE (37.5%) and rV (25%) groups when IP challenged with Y enterocolitica 8081 after 120 days of immunization. Findings in this and our earlier studies define the bivalent fusion protein rVE as a potent candidate vaccine molecule with the capability to concurrently stimulate humoral and cell mediated immune responses and a proof of concept for developing efficient subunit vaccines against Gram negative facultative intracellular bacterial pathogens.show moreshow less

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Metadaten
Author: Amit K. Singh, Joseph J. Kingston, Shishir K. Gupta, Harsh V. Batra
URN:urn:nbn:de:bvb:20-opus-136114
Document Type:Journal article
Faculties:Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Frontiers in Microbiology
Year of Completion:2015
Volume:6
Issue:1407
Source:Frontiers in Microbiology 6:1407. doi:10.3389/fmicb.2015.01407
DOI:https://doi.org/10.3389/fmicb.2015.01407
Dewey Decimal Classification:0 Informatik, Informationswissenschaft, allgemeine Werke / 00 Informatik, Wissen, Systeme / 004 Datenverarbeitung; Informatik
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Tag:CD4+T cells; CD8+T cells; I-tasser; III secretion; V-antigen; Yersinia enterocolitica; cytokine profiling; memory immune responses; mice; nonhuman-primates; pestis infection; pneumonic plague; recombinant protein rVE; resistance; vaccine
Release Date:2016/07/13
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung