Principal neutralizing domain of HIV-1 is highly immunogenic when expressed on the surface of hepatitis B core particles.
The development of subunit vaccines against HIV requires the identification of immunologically relevant antigens and a suitable method of antigen delivery. Ideally, defined epitopes with neutralizing activity should be included in a vaccine preparation. The carrier for such peptide sequences should enhance the immunogenicity of the selected epitopes. In this study hepatitis B virus core antigen (HBcAg) was used as a carrier moiety for the principal neutralizing domain (PND, V3-loop) of HIV-1. A 25 amino acid V3-loop sequence was fused to HBcAg at various positions by genetic engineering. The resulting hybrid HBcAg/HIV polypeptides were analysed for particle formation and immunogenicity. Fusion of the PND to an internal position replacing an immunodominant antibody-binding region of HBcAg or to a C-terminally truncated HBcAg resulted in the formation of hybrid particles with biochemical and biophysical properties similar to those of wild-type HBcAg particles. Both types of hybrids are recognized by monoclonal and polyclonal antisera raised against PND peptides of various HIV-1 isolates. Hybrid particles with a C-terminal fusion but not an internal fusion are also recognized by a polyvalent anti-HBcAg serum. In both cases the V3 domain is surface accessible. Immunization of mice with hybrid particles induces an enhanced antibody response against the V3 sequence. The internal fusion is more immunogenic than the C-terminal fusion.
von Brunn
A
A
Max-von-Pettenkofer-Institut, Ludwig-Maximilians-Universität München, Germany.
Brand
M
M
Reichhuber
C
C
Morys-Wortmann
C
C
Deinhardt
F
F
Schödel
F
F
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002678:Chimera / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D015870:Gene Expression / Q000235:genetics; D015488:HIV Antigens / Q000235:genetics* / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D000939:Epitopes; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D006512:Hepatitis B Core Antigens; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins