Different sources of "help" facilitate the antibody response to hepatitis D virus delta antigen.

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.