Stimulation of Specific Immune Responses to Simian Immunodeficiency Virus Using Chimeric Hepatitis B Core Antigen Particles

Yon, Jeannine; Rud, Erling W.; Corcoran, T.; Kent, Karen; Rowlands, D T; Clarke, Berwyn

doi:10.1099/0022-1317-73-10-2569

Cited by 10 publications

(9 citation statements)

References 25 publications

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“…Interestingly, in chimaeric core particles carrying 90 aa of HIV-1 Gag behind aa position 144 of HBcAg¢, surface-exposed as well as non-exposed regions were mapped [18]. In line with data of Yon et al [7] who did insert an SIV epitope at this position we found the proximal C-terminal insertion site at aa position 183 not to be surface accessible.…”

Section: Discussionsupporting

confidence: 79%

“…Investigations of various insertion sites in HBcAg by the use of different epitopes revealed the c/e1 loop inser-Lachmann/Meisel/Muselmann/Koletzki/ Gelderblom/Borisova/Krüger/Pumpens/ Ulrich tions to be the best in respect of both antigenicity and immunogenicity [5][6][7][8]. However, a systematic study of potential insertion sites in HBcAg by one defined epitope is still missing.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of Potential Insertion Sites in the Core Antigen of Hepatitis B Virus by the Use of a Short-Sized Model Epitope<sup>1</sup>

et al. 1999

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Core particles of hepatitis B virus (HBV) are able to improve the immunogenicity of foreign sequences exposed on the particle surface. The insertion site in the core antigen of HBV (HBcAg) determines the surface presentation and thus the immunogenicity of the foreign sequence. For direct comparison of the value of potential insertion sites in the core antigen, we constructed vectors allowing insertions of a model marker epitope DPAFR. This epitope was inserted at the N-terminus, the c/e1 loop, behind amino acid (aa) 144 and behind aa 183 (DPAF only). In addition, we generated a mosaic construct allowing the co-expression of HBcAg and a HBcAg/DPAFR fusion protein due to a suppressor tRNA-mediated readthrough mechanism. All 6 constructs allowed the formation of chimaeric or mosaic core-like particles. Western blot analyses and a direct ELISA demonstrated the presence of the DPAFR sequence in the chimaeric and mosaic particles. Competitive ELISA and immune electron-microscopic data suggested the c/e1 loop as the insertion site of choice for presenting foreign sequences on the surface of chimaeric HBV core particles. However, the N-terminal fusion also allowed partial surface exposure of the DPAFR motif. In contrast, in particles of constructs carrying the DPAFR insert at aa position 144 or 183, respectively, the epitope seemed not to be surface accessible.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Characterization of Potential Insertion Sites in the Core Antigen of Hepatitis B Virus by the Use of a Short-Sized Model Epitope<sup>1</sup>

et al. 1999

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“…The ability of the HBc chimera to induce FMDV-neutralizing antibodies stimulated authors to construct other N-terminal insertion variants with epi-topes of the gp70 protein of feline leukemia virus, VP2 protein of human rhinovirus type 2, VP1 protein of poliovirus type 1 [98,99], Env protein of simian immunodeficiency virus [100], outer membrane protein P.69 (pertactin) from bacteria Bordetella pertussis [101], and chorionic gonadotropin [97]. The latter was constructed as a contraceptive vaccine candidate.…”

Section: N-terminal Insertionsmentioning

confidence: 99%

“…Historically, the story of MIR insertions started with the introduction of up to 27 aa long epitopes of HBV preS [104,[116][117][118][119][120], 18 aa of VP2 protein from the human rhinovirus type 2 [99,121], up to 30 aa of the simian immunodeficiency virus Env [100], and 25 aa [122,123] and up to 43 aa [119,120] of the V3 loop of the HIV-1 gp120. Insertion of 39 aa of the domain 'a' sequence from the HBsAg (positions 111-149) was the first successful attempt to mimic a conformational epitope on the surface of chimeric particles [124].…”

Section: Internal Insertionsmentioning

confidence: 99%

“…Full-length HBc vectors were used for insertion of fragments from the HBV preS [140][141][142], HIV-1 gp41 [143,144], and simian immunodeficiency virus Env [100]. Further, expression by vaccinia virus of chimeric HBc carrying the long immediate-early CTL epitope from pp89 protein of murine cytomegalovirus (MCMV) at HBc position 179 led to induction of T-lymphocyte-mediated protective immunity against lethal MCMV infection [145].…”

Section: C-terminal Insertionsmentioning

confidence: 99%

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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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