TY  - JOUR
A1  - Singh, Amit K.
A1  - Kingston, Joseph J.
A1  - Gupta, Shishir K.
A1  - Batra, Harsh V.
T1  - Recombinant Bivalent Fusion Protein rVE Induces CD4+ and CD8+ T-Cell Mediated Memory Immune Response for Protection Against Yersinia enterocolitica Infection
JF  - Frontiers in Microbiology
N2  - 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 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.
KW  - I-tasser
KW  - Yersinia enterocolitica
KW  - memory immune responses
KW  - cytokine profiling
KW  - CD8+T cells
KW  - CD4+T cells
KW  - recombinant protein rVE
KW  - resistance
KW  - pneumonic plague
KW  - pestis infection
KW  - nonhuman-primates
KW  - III secretion
KW  - V-antigen
KW  - mice
KW  - vaccine
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136114
VL  - 6
IS  - 1407
ER  - 
TY  - JOUR
A1  - Appel, Mirjam
A1  - Scholz, Claus-Jürgen
A1  - Müller, Tobias
A1  - Dittrich, Marcus
A1  - König, Christian
A1  - Bockstaller, Marie
A1  - Oguz, Tuba
A1  - Khalili, Afshin
A1  - Antwi-Adjei, Emmanuel
A1  - Schauer, Tamas
A1  - Margulies, Carla
A1  - Tanimoto, Hiromu
A1  - Yarali, Ayse
T1  - Genome-Wide Association Analyses Point to Candidate Genes for Electric Shock Avoidance in Drosophila melanogaster
JF  - PLoS ONE
N2  - Electric shock is a common stimulus for nociception-research and the most widely used reinforcement in aversive associative learning experiments. Yet, nothing is known about the mechanisms it recruits at the periphery. To help fill this gap, we undertook a genome-wide association analysis using 38 inbred Drosophila melanogaster strains, which avoided shock to varying extents. We identified 514 genes whose expression levels and/or sequences covaried with shock avoidance scores. We independently scrutinized 14 of these genes using mutants, validating the effect of 7 of them on shock avoidance. This emphasizes the value of our candidate gene list as a guide for follow-up research. In addition, by integrating our association results with external protein-protein interaction data we obtained a shock avoidance- associated network of 38 genes. Both this network and the original candidate list contained a substantial number of genes that affect mechanosensory bristles, which are hairlike organs distributed across the fly's body. These results may point to a potential role for mechanosensory bristles in shock sensation. Thus, we not only provide a first list of candidate genes for shock avoidance, but also point to an interesting new hypothesis on nociceptive mechanisms.
KW  - functional analysis
KW  - disruption project
KW  - natural variation
KW  - complex traits
KW  - networks
KW  - behavior
KW  - flies
KW  - temperature
KW  - genetics
KW  - painful
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-152006
VL  - 10
IS  - 5
ER  -