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Different sources of “help” facilitate the antibody response to hepatitis D virus δ antigen

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Abstract

Repeated injections of hepatitis D antigen (HDAg) delivered either as a recombinant protein, or expressed from a DNA vaccine elicited no (or only very low) antibody responses in inbred mouse strains. Codelivery of oligonucleotides (ODN) with immune-stimulating sequences (ISS) with the protein antigen, or ISS in DNA vaccines (encoding HDAg) did not overcome the low intrinsic immunogenicity of this small viral antigen for B cells. In contrast, codelivery of immunogenic, heterologous proteins (either mixed to recombinant HDAg as recombinant proteins, or fused to HDAg sequences as chimeric antigens expressed from DNA vaccines) provided specific, CD4+ T cell-dependent “help” that supported efficient priming of antibody responses to HDAg. Chimeric proteins in which selected HDAg fragments were fused in frame with immunogenic, heterologous protein fragments produced by DNA vaccines allowed the mapping of antibody-binding HDAg domains of the viral antigen. The described approach thus facilitates induction of serum antibody responses against native viral antigens with low immunogenicity for B cells

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Abbreviations

eGFP :

Enhanced green fluorescence protein

ELISA :

Enzyme-linked immunosorbent assay

hCMV-IE :

Human cytomegalovirus immediate early

HBcAg :

Hepatitis B core antigen

HBsAg :

Hepatitis B surface antigen

HBV :

Hepatitis B virus

HDV :

Hepatitis D virus

HDAg :

Hepatitis D or δ antigen

L-HDAg :

Large p27 HDAg

S-HDAg :

Small p24 HDAg

hsp :

Heat shock protein

ISS :

Immune-stimulating (CpG-containing) sequence

mAb :

Monoclonal antibody

ODN :

Oligodeoxynucleotide

OVA :

Ovalbumin

PAGE :

Polyacrylamide gel electrophoresis

SDS :

Sodium dodecyl sulfate

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Acknowledgements

This work is supported by a grant from the Deutsche Forschungsgemeinschaft to R.S. (DFG Schi 505/2-2). The excellent technical assistance of Ms. T. Güntert and K. Ölberger are greatly appreciated.

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Authors and Affiliations

  1. Institute for Medical Microbiology and Immunology, University of Ulm, Albert Einstein Allee 11, 89081, Ulm, Germany

    Peter Seizer, Petra Riedl, Jörg Reimann & Reinhold Schirmbeck

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  1. Peter Seizer
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  2. Petra Riedl
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  3. Jörg Reimann
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  4. Reinhold Schirmbeck
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Correspondence to Reinhold Schirmbeck.

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Seizer, P., Riedl, P., Reimann, J. et al. Different sources of “help” facilitate the antibody response to hepatitis D virus δ antigen. J Mol Med 83, 225–234 (2005). https://doi.org/10.1007/s00109-004-0598-0

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  • DOI: https://doi.org/10.1007/s00109-004-0598-0

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