High immunogenicity of a hydrophilic component of the hepatitis B virus preS1 sequence exposed on the surface of three virus-like particle carriers

Skrastiņa, Dace; Bulavaitė, Aistė; Sominskaya, Irina; Kovalevska, Larisa; Ose, Velta; Priede, Dace; Pumpens, Paul; Sasnauskas, Kęstutis

doi:10.1016/j.vaccine.2008.02.030

Cited by 27 publications

(26 citation statements)

References 35 publications

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“…1) and expressed in Escherichia coli [29,49]. Nearly all preS1-core fusion proteins formed CLPs as determined by electron microscopy (data not shown), except for the insertion of the hydrophobic preS1(48-73) region.…”

Section: Generation Of Capsid-like Particles (Clps)mentioning

confidence: 92%

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N-terminal myristoylation-dependent masking of neutralizing epitopes in the preS1 attachment site of hepatitis B virus

Bremer

Sominskaya

Skrastiņa

et al. 2011

Journal of Hepatology

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Section: Generation Of Capsid-like Particles (Clps)mentioning

confidence: 92%

“…Foreign epitopes inserted at the tip induce a strong and specific T-and B-cell immunity [43]. Inserted preS1 epitopes elicited a specific antibody response without addition of adjuvants [7,29,49]. The binding capacity to native HBs proteins and the HBV-neutralizing potential of these antibodies has not yet been determined.…”

Section: Introductionmentioning

confidence: 99%

N-terminal myristoylation-dependent masking of neutralizing epitopes in the preS1 attachment site of hepatitis B virus

Bremer

Sominskaya

Skrastiņa

et al. 2011

Journal of Hepatology

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“…Another option would be the inclusion of neutralizing preS epitopes which are less prone to immune escape. Since the preS peptides are not very immunogenic by themselves, these epitopes have been presented on the very immunogenic HBV core particles [32] . This type of antigen induced very high titers of neutralizing antibodies in mice [Bremer et al, submitted], and may be considered a candidate for a new generation of hepatitis B vaccine.…”

Section: Obi In Vaccinated Blood Donorsmentioning

confidence: 99%

Occult Hepatitis B Virus Infection: Detection and Significance

Gerlich

Bremer²,

Saniewski³

et al. 2010

Dig Dis

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The Taormina Consensus Conference defined ‘occult hepatitis B virus (HBV) infection’ (OBI) as the ‘presence of HBV DNA in the liver of individuals testing HBsAg-negative with currently available assays’. Most occult is the so-called ‘window period’ after exposure before HBV DNA appears in the blood. We identified two blood donors whose donations tested HBsAg- and HBV DNA-negative, but transmitted HBV. Both subsequently developed HBsAg and acute hepatitis. However, such cases are not considered as true OBI. A true transient OBI remains HBsAg-negative during the entire course. One case of acute OBI showed a peak viremia of 15,000 IU/ml HBV DNA and sub-borderline HBsAg, suggesting a ratio of virions to subviral particles of 1:10, whereas ‘normal’ cases show at peak viremia a ratio of 1:3,000. Blood donors with OBI may transmit HBV. We studied 5 blood donors with OBI and 55 of their recipients. In 22 recipients, transmission was probable, but they remained healthy. However, in 3 recipients, who were immunosuppressed at the time of transfusion, fatal fulminant hepatitis B developed. The majority of anti-HBc-positive healthy individuals have HBV DNA in the liver which may start replication under severe immunosuppression. Nine such cases are described here. OBI or reactivated HBV infections often lead to selection of HBsAg escape mutations as we could show in 11 of 14 cases. Infection of vaccinated individuals favors development of OBI as we observed in 6 blood donors. HB vaccination may solve the problem of overt HBV infection but may favor OBI.

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“…Further, three tandem copies of pre-S1 (21-47) were inserted at the MIR (44). Moreover, practically full-length pre-S1, with deletion of the inner hydrophobic membrane-targeting fragment, was exposed on the surfaces of the HBc and HBc⌬ VLPs (35). In addition, numerous variants of mosaic HBc particles carrying the complete pre-S sequence at the MIR have been constructed with and without MIR deletions (16).…”

Section: Discussionmentioning

confidence: 99%

Construction and Immunological Evaluation of Multivalent Hepatitis B Virus (HBV) Core Virus-Like Particles Carrying HBV and HCV Epitopes

Sominskaya

Skrastiņa

Dislers

et al. 2010

Clin Vaccine Immunol

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A multivalent vaccine candidate against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections was constructed on the basis of HBV core (HBc) virus-like particles (VLPs) as carriers. Chimeric VLPs that carried a virus-neutralizing HBV pre-S1 epitope corresponding to amino acids (aa) 20 to 47 in the major immunodominant region (MIR) and a highly conserved N-terminal HCV core epitope corresponding to aa 1 to 60 at the C terminus of the truncated HBc⌬ protein (N-terminal aa 1 to 144 of full-length HBc) were produced in Escherichia coli cells and examined for their antigenicity and immunogenicity. The presence of two different foreign epitopes within the HBc molecule did not interfere with its VLP-forming ability, with the HBV pre-S1 epitope exposed on the surface and the HCV core epitope buried within the VLPs. After immunization of BALB/c mice, specific T-cell activation by both foreign epitopes and a high-titer antibody response against the pre-S1 epitope were found, whereas an antibody response against the HBc carrier was notably suppressed. Both inserted epitopes also induced a specific cytotoxic-T-lymphocyte (CTL) response, as shown by the gamma interferon (IFN-␥) production profile.Genetically engineered virus-like particle (VLP)-based vaccines are one of the most promising tools in modern vaccinology. VLPs from almost all classes of viruses are being evaluated now or have just been adopted to use as carriers for presentation of foreign immunological epitopes (for a review, see references 29 and 31). VLP technologies possess obvious advantages for the generation of safe and efficacious vaccines. First, the repetitive antigenic structure of VLPs makes them highly immunogenic. Second, VLPs lack viral genomes or genes and are noninfectious, although they mimic infectious viruses in their structural and immunological features. Third, VLPs are generated by highly efficient heterologous expression of the cloned viral structural genes with subsequent quantitative in vivo or in vitro self-assembly of their products. Fourth, VLPs can be obtained by simple and efficient purification procedures. VLPs can be used for a broad range of applications, but the generation of vaccines against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is of special interest.The HBV core (HBc) protein was first reported as a promising VLP carrier in 1986 and was published in 1987 (6, 10, 24). In many ways, HBc occupies a unique position among the VLP carriers because of its high-level synthesis and efficient selfassembly in virtually all known homologous and heterologous expression systems, including bacteria (for a review, see references 29 to 31). The major HBc B-cell epitopes (c and e1) are localized within the major immunodominant region (MIR), whereas the next important epitope, e2, is localized around amino acid position 130, close to the C-terminal histone-like region (for a review, see reference 30).The high-resolution spatial structure of HBc icosahedrons (11,43) shows that the MIR is located on the tip of th...

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High immunogenicity of a hydrophilic component of the hepatitis B virus preS1 sequence exposed on the surface of three virus-like particle carriers

Cited by 27 publications

References 35 publications

N-terminal myristoylation-dependent masking of neutralizing epitopes in the preS1 attachment site of hepatitis B virus

N-terminal myristoylation-dependent masking of neutralizing epitopes in the preS1 attachment site of hepatitis B virus

Occult Hepatitis B Virus Infection: Detection and Significance

Construction and Immunological Evaluation of Multivalent Hepatitis B Virus (HBV) Core Virus-Like Particles Carrying HBV and HCV Epitopes

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