Priming biologically active antibody responses against an isolated, conformational viral epitope by DNA vaccination.
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 (T(77)) or non-hsp-binding 60 aa (T(60)) N terminus. A DNA vaccine encoding non-hsp-binding secreted T(60)-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 T(77)-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 T(60)-SII-expressing or the T(77)-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 S(20-50) fragment (containing the immunodominant, L(d)-binding epitope S(28-39)) of HBsAg was fused C-terminally to the pCI/T(77)-SII sequence (pCI/T(77)-SII-L(d) 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.
Institute of Medical Microbiology and Immunology, University of Ulm, Ulm, Germany.
Petra
P
Riedl
Shereen
S
El-Kholy
Jörg
J
Reimann
Reinhold
R
Schirmbeck
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006510:Hepatitis B Antibodies / Q000096:biosynthesis*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D000952:Antigens, Polyomavirus Transforming; D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D015395:Histocompatibility Antigens Class I; C494372:Hspa8 protein, mouse; D010446:Peptide Fragments; D019444:Vaccines, DNA