Unusually high-level expression of a foreign gene (hepatitis B virus core antigen) in Saccharomyces cerevisiae

Pj, Kniskern; Hagopian, Arpi; Dl, Montgomery; Burke, P; Nr, Dunn; Kj, Hofmann; Wj, Miller; Rw, Ellis

doi:10.1016/0378-1119(86)90177-0

Cited by 85 publications

(33 citation statements)

References 14 publications

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“…Furthermore, in samples with high levels of antibody against the peptide [>3.5 logarithmic (to base 10) units] some low levels of neutralizing activity [up to 1.7 logarithmic (to base 10) units of neutralization at a 50o endpoint against 100 tissue culture 50% infective dose of virus] were seen. However, the ratio of antipeptide antibody to virus neutralizing antibody of =100:1 was no better than that seen previously (17) with KLH-coupled synthetic HRV2 peptide.…”

Section: Discussionmentioning

confidence: 99%

“…The protein subunit is a 21-kDa polypeptide (7,8) that spontaneously assembles into characteristic 27-nm particles (9) and can be expressed in a wide range of systems, including bacterial cell (8), yeast cell (10), and mammalian cell (11), or via vaccinia virus (1,6), and baculovirus (12). The core particle is known to be highly immunogenic (13), possibly due to its polymeric nature, the presence of a number of welldefined helper T-cell epitopes (14), and its ability to function as a T-cell independent antigen (15).…”

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confidence: 99%

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Immunological properties of hepatitis B core antigen fusion proteins.

Francis

Hastings

Brown

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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The immunogenicity of a 19 amino acid peptide from foot-and-mouth disease virus has previously been shown to approach that of the inactivated virus from which it was derived after multimeric particulate presentation as an N-terminal fusion with hepatitis B core antigen. In this report we demonstrate that rhinovirus peptide-hepatitis B core antigen fusion proteins are 10-fold more immunogenic than peptide coupled to keyhole limpet hemocyanin and 100-fold more immunogenic than uncoupled peptide with an added helper T-cell epitope. The fusion proteins can be readily administered without adjuvant or with adjuvants acceptable for human and veterinary application and can elicit a response after nasal or oral dosing. The fusion proteins can also act as T-cell-independent antigens. These properties provide further support for their suitability as presentation systems for "foreign" epitopes in the development of vaccines.An important consideration for designing vaccines based on defined peptides from complex protein antigens is their optimal delivery to the immune system to produce maximal antibody response, both qualitatively and quantitatively. This requirement has resulted in the development of various polymeric presentation systems based on recombinant DNA technology-for example, core-(1, 2) and surface-antigen (3) particles from hepatitis B virus, poliovirus particles (4), and yeast transposon Ty proteins (5).The use of the core antigen from hepatitis B virus (HBcAg) to present "foreign" peptide epitopes, first described by Newton et al. (6) in 1986, offers several potential advantages. The protein subunit is a 21-kDa polypeptide (7,8) that spontaneously assembles into characteristic 27-nm particles (9) and can be expressed in a wide range of systems, including

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Immunological properties of hepatitis B core antigen fusion proteins.

Francis

Hastings

Brown

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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“…Correct folding of the HBc protein and formation of authentic HBc particles have been documented in various mammalian cell cultures [13][14][15][16][17][18], retrovirus [19], vaccinia virus [20,21] and adenovirus [22] expression systems, frog Xenopus oocytes [23], insect Spodoptera cells [24][25][26][27], yeast Saccharomyces cerevisiae [28][29][30][31], in plants Nicotiana tabacum [32], and in bacteria such as Escherichia coli [33][34][35][36][37][38][39][40][41][42], Bacillus subtilis [43], Salmonella [44] and Acetobacter [45]. Electron microscopy revealed the ultrastructural identity of the HBc particles derived from either HBV virions and infected hepatocytes, or from E. coli [46] or yeast [47].…”

Section: Introductionmentioning

confidence: 99%

HBV Core Particles as a Carrier for B Cell/T Cell Epitopes

Pumpens¹,

Grens²

2001

Intervirology

250

195

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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 α-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.

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“…Properties of hepatitis B core antigen (HBcAg) which make it suitable for the purpose described above include the ability of the 21K monomer to self-assemble into 27 nm particles when expressed in a variety of prokaryotic and eukaryotic systems (Pasek et al, 1979;Kniskern et al, 1986;Lanford et al, 1989;Clarke et al, 1987). The core fusion particle (CFP) is a versatile carrier: particles have been described in which peptides were inserted at one of three different sites in the molecule, either as N-terminal fusions (Clarke et al, 1987), truncated C-terminal fusions (Stahl & Murray, 1989) or within an internal immunodominant region (Schodel et al, 1992;Brown et al, 1991).…”

Section: Introductionmentioning

confidence: 99%