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  • 1
    Keywords: MODEL ; MODELS ; GENE ; DRUG ; MOLECULES ; GENE-TRANSFER ; DNA ; DENDRITIC CELLS ; T-CELLS ; BIOLOGY ; MOLECULE ; ACID ; ACIDS ; NEUTRALIZING ANTIBODIES ; NUCLEIC-ACIDS ; PARTICLES ; virus ; VIRUS-LIKE PARTICLES ; SURFACE ; DELIVERY ; VACCINE ; VESSELS ; CROSS-PRESENTATION ; review ; OLIGONUCLEOTIDE ; DRUG-DELIVERY ; CELLULAR IMMUNE-RESPONSES ; PAPILLOMAVIRUS-LIKE PARTICLES ; SUCCINIMIDYL ESTER
    Abstract: Virus-like particles (VLPs) structurally mimic the viral capsid and have therefore been extensively, and quite successfully, used as vaccine and viral serology reagents. The ability of VLPs to include nucleic acids and small molecules has also made them novel vessels for gene and drug delivery. The regular, repetitive surface of VLPs has been exploited as a template for nanoscale synthesis. Recent progress has been made in the development of several virus models
    Type of Publication: Journal article published
    PubMed ID: 15560977
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  • 2
    Keywords: PEPTIDE ; CELLS ; EXPRESSION ; IN-VITRO ; tumor ; TUMOR-CELLS ; Germany ; human ; PROTEIN ; PROTEINS ; TUMORS ; MICE ; RELEASE ; COMPLEX ; RESPONSES ; COMPLEXES ; SERA ; REDUCTION ; DENDRITIC CELLS ; BINDING ; SEQUENCE ; antibodies ; NEUTRALIZING ANTIBODIES ; PARTICLES ; ASSAY ; ESCHERICHIA-COLI ; GLUTATHIONE ; LYMPHOCYTES ; VIRUS-LIKE PARTICLES ; HPV ; HPV16 ; VACCINE ; IMMUNE-RESPONSE ; vaccination ; L1 ; SEQUENCE-ANALYSIS ; glutathione-S-transferase ; HPV PSEUDOVIRIONS ; NASAL IMMUNIZATION
    Abstract: We analyzed capsomeres of human papillomavirus type 16 (HPV16) consisting of the L1 major structural protein for their ability to trigger a cytotoxic T-cell (CTL) response. To this end, we immunized C57BL/6 mice and used the L1(165-173) peptide for ex vivo restimulation of splenocytes prior to analysis (Cr-51 release assay and enzyme-linked immunospot assay [ELISPOT]). This peptide was identified in this study as a D-b-restricted naturally processed CTL epitope by HPV16 L1 sequence analysis, major histocompatibility complex class I binding, and Cr-51 release assays following immunization of C57BL/6 mice with HPV16 L1 virus-like particles (VLPs). HPV16 L1 capsomeres were obtained by purification of HPV16 L1 lacking 10 N-terminal amino acids after expression in Escherichia coli as a glutathione S-transferase fusion protein (GST-HPV16 L1DeltaN10). Sedimentation analysis revealed that the majority of the purified protein consisted of pentameric capsomeres, and assembled particles were not observed in minor contaminating higher-molecular-weight material. Subcutaneous (s.c.) as well as intranasal immunization of C57BL/6 m ice with HPV16 L1 capsomeres triggered an L1-specific CTL response in a dose- dependent manner as measured by ELISPOT and Cr-51 release as say. Significant reduction of contaminating bacterial endotoxin (lipopolysaccharide) from the capsomere preparation did not diminish the immunogenicity. Antibody responses (serum and vaginal) were less robust under the experimental conditions employed. In addition, s.c. vaccination with HPV16 L1 capsomeres induced regression of established tumors expressing L1 determinants (C3 tumor cells). Our data demonstrate that capsomeres are potent inducers of CTL responses similar to completely assembled T=7 VLPs. This result is of potential relevance for the development of (combined prophylactic and therapeutic) HPV-specific vaccines, since capsomeres can be produced easily and also can be modified to incorporate heterologous sequences such as early HPV proteins
    Type of Publication: Journal article published
    PubMed ID: 12663770
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  • 3
    Keywords: CANCER ; EXPRESSION ; PROTEIN ; SACCHAROMYCES-CEREVISIAE ; INFECTION ; IMMUNE-RESPONSES ; WOMEN ; ORAL IMMUNIZATION ; CYTOTOXIC T-LYMPHOCYTES ; review ; N-TERMINUS ; MINOR CAPSID PROTEIN ; SUSTAINED EFFICACY ; CROSS-NEUTRALIZING EPITOPE ; TYPE-16 L1 PROTEIN ; VIRUS-LIKE-PARTICLES
    Abstract: The currently licensed human papillomavirus (HPV) vaccines are safe and highly effective at preventing HPV infection for a select number of papillomavirus types, thus decreasing the incidence of precursors to cervical cancer. It is expected that vaccination will also ultimately reduce the incidence of this cancer. The licensed HPV vaccines are, however, type restricted and expensive, and also require refrigeration, multiple doses and intramuscular injection. Second-generation vaccines are currently being developed to address these shortcomings. New expression systems, viral and bacterial vectors for HPV L1 capsid protein delivery, and use of the HPV L2 capsid protein will hopefully aid in decreasing cost and increasing ease of use and breadth of protection. These second-generation vaccines could also allow affordable immunization of women in developing countries, where the incidence of cervical cancer is high
    Type of Publication: Journal article published
    PubMed ID: 22293302
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