Immunization with HBsAg-Fc fusion protein induces a predominant production of Th1 cytokines and reduces HBsAg level in transgenic mice / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 3266-3272, 2012.
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| WPRIM
| ID: wpr-316525
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ABSTRACT
<p><b>BACKGROUND</b>The Fc receptor associated pathway might improve the immune responses against hepatitis B virus (HBV) as previously described by us. In addition, the Flt3 ligand (FL) has been reported to potentiate antigen presenting cells in vivo and may act as a potential adjuvant to boost antigen-specific immune responses. In this study, the immune efficacies of a set of fusion proteins of HBsAg and Fc and/or FL were evaluated in HBsAg transgenic mice.</p><p><b>METHODS</b>The fusion proteins composed of HBsAg and the Fc domain of murine IgG1 (HBsAg-Fc) and/or the Flt3 ligand, and yeast-derived recombinant HBsAg were used as immunogen to immunize HBsAg transgenic mice, respectively. Serum and liver HBsAg levels, serum anti-HBsAg and cytokine profile, and the activities of alanine aminotransferase (ALT)/AST were investigated after immunization.</p><p><b>RESULTS</b>After six injections, the most pronounced decrease in serum and liver HBsAg levels was observed in the HBsAg-Fc immunized group. In addition, serum Th1 cytokines and ALT/AST activities were highest in this group, indicating an effective induction of a favorable cellular immune response. Interestingly, the fusion protein containing HBsAg-Fc and the Flt3 ligand stimulated an alternative Th1-type immune response featured with high level productions of tumor necrosis factor α (TNF-α) and monocyte chemoabstractant protein 1 (MCP-1), causing a more severe cytotoxicity in hepatocytes while showed less effective in reducing serum HBsAg level.</p><p><b>CONCLUSION</b>HBsAg-Fc is effective in eliciting both the humoral and cellular immune responses against HBsAg in HBsAg transgenic mice, which makes it a potential immunogen for the immunotherapy of chronic hepatitis B.</p>
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WPRIM
Asunto principal:
Proteínas Recombinantes de Fusión
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Ensayo de Inmunoadsorción Enzimática
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Ratones Transgénicos
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Receptores Fc
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Citocinas
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Factor de Necrosis Tumoral alfa
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Quimiocina CCL2
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Alergia e Inmunología
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Inmunidad Humoral
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Genética
Límite:
Animals
Idioma:
En
Revista:
Chinese Medical Journal
Año:
2012
Tipo del documento:
Article