Foreign epitopes in immunodominant regions of hepatitis B core particles are highly immunogenic and conformationally restricted.
The presentation of heterologous amino acid sequences on the surface of hepatitis B core antigen (HBcAg) particles has been studied using a defined linear neutralization site from human rhinovirus (HRV). Previous work has shown that fusion particles, in which the HRV peptide sequence is linked to the amino terminus of the HBcAg protein, induce excellent immune responses in experimental animals. Using predictive models of HBcAg particulate structure and the approximate location of the major immunogenic regions we have designed and constructed bacterial expression vectors which direct synthesis of chimeric particles in which heterologous sequences are presented within an immunodominant area on the particle. Immunological responses to the heterologous peptide sequence are improved by at least tenfold when compared with amino terminal fusions of the same peptide sequence to HBcAg. Moreover, the restriction placed on the heterologous peptide by its linkage at both ends within the HBcAg protein results in a more constrained structure. In the case of the rhinovirus peptide sequence this results in an antigenic conformation more closely resembling that on the native virus particle. Such a system lends itself well as a general approach to the induction of high titre antibodies against defined epitopes.
Brown
A L
AL
Department of Virology, Wellcome Research Laboratories, Beckenham, Kent, UK.
Francis
M J
MJ
Hastings
G Z
GZ
Parry
N R
NR
Barnett
P V
PV
Rowlands
D J
DJ
Clarke
B E
BE
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D015153:Blotting, Western; D004274:DNA, Recombinant / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics*; D005260:Female; D005822:Genetic Vectors; D006168:Guinea Pigs; D006512:Hepatitis B Core Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D010957:Plasmids; D011487:Protein Conformation; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012229:Rhinovirus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014611:Vaccination
D000914:Antibodies, Viral; D000956:Antigens, Viral; D004274:DNA, Recombinant; D000939:Epitopes; D006512:Hepatitis B Core Antigens; D011993:Recombinant Fusion Proteins