Dataset Information

Enrichment of Ly6C^hi monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model.

ABSTRACT: Adjuvants are considered a necessary component for HBV therapeutic vaccines but few are licensed in clinical practice due to concerns about safety or efficiency. In our recent study, we established that a combination protocol of 3-day pretreatments with GM-CSF before a vaccination (3 × GM-CSF+VACCINE) into the same injection site could break immune tolerance and cause over 90% reduction of HBsAg level in the HBsAg transgenic mouse model. Herein, we further investigated the therapeutic potential of the combination in AAV8-1.3HBV-infected mice. After 4 vaccinations, both serum HBeAg and HBsAg were cleared and there was a 95% reduction of HBV-positive hepatocytes, in addition to the presence of large number of infiltrating CD8⁺ T cells in the livers. Mechanistically, the HBV-specific T-cell responses were elicited via a 3 × GM-CSF+VACCINE-induced conversion of CCR2-dependent CD11b⁺ Ly6C^hi monocytes into CD11b⁺CD11c⁺ DCs. Experimental depletion of Ly6C^hi monocytes resulted in a defective HBV-specific immune response thereby abrogating HBV eradication. This vaccination strategy could lead to development of an effective therapeutic protocol against chronic HBV in infected patients.

SUBMITTER: Zhao W

PROVIDER: S-EPMC5718782 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Enrichment of Ly6C<sup>hi</sup> monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model.

Zhao Weidong W Zhou Xian X Zhao Gan G Lin Qing Q Wang Xianzheng X Yu Xueping X Wang Bin B

Human vaccines & immunotherapeutics 20170712 12

Adjuvants are considered a necessary component for HBV therapeutic vaccines but few are licensed in clinical practice due to concerns about safety or efficiency. In our recent study, we established that a combination protocol of 3-day pretreatments with GM-CSF before a vaccination (3 × GM-CSF+VACCINE) into the same injection site could break immune tolerance and cause over 90% reduction of HBsAg level in the HBsAg transgenic mouse model. Herein, we further investigated the therapeutic potential ...[more]

PMID: 28699816

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Project description:Heme oxygenase-1 (Hmox1) is a stress-inducible protein crucial in heme catabolism. The end products of its enzymatic activity possess anti-oxidative, anti-apoptotic and anti-inflammatory properties. Cardioprotective effects of Hmox1 were demonstrated in experimental models of myocardial infarction (MI). Nevertheless, its importance in timely resolution of post-ischemic inflammation remains incompletely understood. The aim of this study was to determine the role of Hmox1 in the monocyte/macrophage-mediated cardiac remodeling in a mouse model of MI. Hmox1 knockout (Hmox1-/-) and wild-type (WT, Hmox1+/+) mice were subjected to a permanent ligation of the left anterior descending coronary artery. Significantly lower incidence of left ventricle (LV) free wall rupture was noted between 3rd and 5th day after MI in Hmox1-/- mice resulting in their better overall survival. Then, starting from 7th until 21st day post-MI a more potent deterioration of LV function was observed in Hmox1-/- than in the surviving Hmox1+/+ mice. This was accompanied by higher numbers of Ly6Chi monocytes in peripheral blood, as well as higher expression of monocyte chemoattractant protein-1 and adhesion molecules in the hearts of MI-operated Hmox1-/- mice. Consequently, a greater post-MI monocyte-derived myocardial macrophage infiltration was noted in Hmox1-deficient individuals. Splenectomy decreased the numbers of circulating inflammatory Ly6Chi monocytes in blood, reduced the numbers of proinflammatory cardiac macrophages and significantly improved the post-MI LV function in Hmox1-/- mice. In conclusion, Hmox1 deficiency has divergent consequences in MI. On the one hand, it improves early post-MI survival by decreasing the occurrence of cardiac rupture. Afterwards, however, the hearts of Hmox1-deficient mice undergo adverse late LV remodeling due to overactive and prolonged post-ischemic inflammatory response. We identified spleen as an important source of these cardiovascular complications in Hmox1-/- mice.

Dataset Information

Enrichment of Ly6C^hi monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model.

Publications

Enrichment of Ly6C<sup>hi</sup> monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model.

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Dataset Information

Enrichment of Ly6Chi monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model.

Publications

Enrichment of Ly6C<sup>hi</sup> monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Enrichment of Ly6C^hi monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model.