Priming Biologically Active Antibody Responses Against an Isolated, Conformational Viral Epitope by DNA Vaccination
| Autor: | Petra Riedl, Shereen El Kholy, Jörg Reimann, Reinhold Schirmbeck |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
HBsAg
Antigens Polyomavirus Transforming Immunology Priming (immunology) Epitope DNA vaccination Mice Viral envelope Antigen MHC class I Vaccines DNA Animals Immunology and Allergy HSP70 Heat-Shock Proteins Hepatitis B Vaccines Hepatitis B Antibodies Mice Inbred BALB C Hepatitis B Surface Antigens biology Histocompatibility Antigens Class I HSC70 Heat-Shock Proteins virus diseases Virology Molecular biology Fusion protein Peptide Fragments Mice Inbred C57BL biology.protein Immunization Carrier Proteins T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Immunology. 169:1251-1260 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.169.3.1251 |
| Popis: | The immunodominant, conformational “a” determinant of hepatitis B surface Ag (HBsAg) elicits Ab responses. We selectively expressed the Ab-binding, glycosylated, native a determinant (residue 120–147) of HBsAg in a fusion protein containing C-terminally the HBsAg fragment SII (residue 80–180) fused to a SV40 T-Ag-derived hsp73-binding 77 aa (T77) or non-hsp-binding 60 aa (T60) N terminus. A DNA vaccine encoding non-hsp-binding secreted T60-SII fusion protein-stimulated murine Ab responses with a similar efficacy as a DNA vaccine encoding the secreted, native, small HBsAg. A DNA vaccine encoding hsp73-binding, intracellular T77-SII fusion protein-stimulated murine Ab responses less efficiently but comparable to a DNA vaccine encoding the intracellular, native, large HBsAg. HBsAg-specific Abs elicited by either the T60-SII-expressing or the T77-SII-expressing DNA vaccine suppressed HBsAg antigenemia in transgenic mice that produce HBsAg from a transgene in the liver; hence, a biologically active B cell response cross-reacting with the native, viral envelope epitope was primed by both DNA vaccine constructs. HBsAg-specific Ab and CTL responses were coprimed when an S20–50 fragment (containing the immunodominant, Ld-binding epitope S28–39) of HBsAg was fused C-terminally to the pCI/T77-SII sequence (pCI/T77-SII-Ld DNA vaccine). Chimeric, polyepitope DNA vaccines encoding conformational, Ab-binding epitopes and MHC class I-binding epitopes can thus efficiently deliver antigenic information to different compartments of the immune system in an immunogenic way. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|