HBV core particles as a carrier for B cell/T cell epitopes.
In the middle 80s, recombinant hepatitis B virus cores (HBc) gave onset to icosahedral virus-like particles (VLPs) as a basic class of non-infectious carriers of foreign immunological epitopes. The recombinant HBc particles were used to display immunodominant epitopes of hepatitis B, C, and E virus, human rhinovirus, papillomavirus, hantavirus, and influenza virus, human and simian immunodeficiency virus, bovine and feline leukemia virus, foot-and-mouth disease virus, murine cytomegalovirus and poliovirus, and other virus proteins, as well as of some bacterial and protozoan protein epitopes. Practical applicability of the HBc particles as carriers was enabled by their ability to high level synthesis and correct self-assembly in heterologous expression systems. The interest in the HBc VLPs was reinforced by the resolution of their fine structure by electron cryomicroscopy and X-ray crystallography, which revealed an unusual alpha-helical organization of dimeric units of HBc shells, alternative packing into icosahedrons with T = 3 and T = 4 symmetry, and the existence of long protruding spikes. The tips of the latter seem to be the optimal targets for the display of foreign sequences up to 238 amino acid residues in length. Combination of numerous experimental data on epitope display with the precise structural information enables a knowledge-based design of diagnostic, and vaccine and gene therapy tools on the basis of the HBc particles.
Pumpens
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P
Biomedical Research and Study Center, University of Latvia, Riga, Latvia. paul@biomed.lu.lv
Grens
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E
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015316:Genetic Therapy; D006515:Hepatitis B virus / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins / Q000378:metabolism; D014765:Viral Vaccines
D000956:Antigens, Viral; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014765:Viral Vaccines