The Experts below are selected from a list of 465 Experts worldwide ranked by ideXlab platform
Neil D Christensen - One of the best experts on this subject based on the ideXlab platform.
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Antiviral Chemistry & Chemotherapy 16:355–362
2016Co-Authors: Neil D ChristensenAbstract:Cottontail Rabbit Papillomavirus (CRPV) model system to test antiviral and immunotherapeutic strategie
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Long-peptide therapeutic vaccination against CRPV-induced papillomas in HLA-A2.1 transgenic Rabbits
Elsevier, 2014Co-Authors: Lynn R. Budgeon, Nancy M Cladel, Xuwen Peng, Karla K. Balogh, Neil D ChristensenAbstract:Long peptide immunization is a promising strategy to clear established tumors. In the current study, we investigated the therapeutic effect of a naturally existing long peptide that contained two HLA-A2.1 restricted epitopes (CRPVE1/149–157 and CRPVE1/161–169) from Cottontail Rabbit Papillomavirus (CRPV) E1 using our CRPV/HLA-A2.1 transgenic Rabbit model. A universal Tetanus Toxin helper motif (TT helper) was tagged at either the N-terminus or the carboxyl-terminus of this long peptide and designated as TT-E1 peptide and E1 peptide-TT, respectively. Four groups of HLA-A2.1 transgenic Rabbits were infected with wild type CRPV DNA. Three weeks post-infection, the Rabbits were immunized four times with TT-E1 peptide, E1 peptide only, E1 peptide-TT or TT-control peptide with two-week intervals between immunizations. Tumor outgrowth was monitored and recorded weekly. After the third booster immunization, tumors on two of the four E1 peptide-TT immunized Rabbits began to shrink. One animal from this group was free of tumors at the termination of the study. The mean papilloma size of E1 peptide-TT immunized Rabbits was significantly smaller when compared with that of the three other groups (P
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protective immunity with an e1 multivalent epitope dna vaccine against Cottontail Rabbit Papillomavirus crpv infection in an hla a2 1 transgenic Rabbit model
Vaccine, 2008Co-Authors: Nancy M Cladel, Xuwen Peng, Karla K. Balogh, Neil D ChristensenAbstract:Cottontail Rabbit Papillomavirus (CRPV)/Rabbit model is widely used to study pathogenesis of Papillomavirus infections and malignant tumor progression. Recently, we established HLA-A2.1 transgenic Rabbit lines and demonstrated efficacy for the testing of immunogenicity of a well-known A2-resticted epitope (HPV16E7/82-90) [Hu J, Peng X, Schell TD, Budgeon LR, Cladel NM, Christensen ND. An HLA-A2.1-transgenic Rabbit model to study immunity to Papillomavirus infection. J Immunol 2006;177(11):8037-45]. In the present study, we screened five HLA-A2.1 restricted epitopes from CRPVE1 (selected using online MHCI epitope prediction software) and constructed a multivalent epitope DNA vaccine (CRPVE1ep1-5). CRPVE1ep1-5 and a control DNA vaccine (Ub3) were then delivered intracutaneously onto normal and HLA-A2.1 transgenic Rabbits, respectively, by a helium-driven gene-gun delivery system. One, two or three immunizations were given to different groups of animals from both New Zealand White outbred and EIII/JC inbred genetic background. Two and three immunizations with CRPVE1ep1-5 DNA vaccine provided complete protection against viral DNA infection of HLA-A2.1 transgenic Rabbits from both genetic backgrounds but not in the control-vaccinated groups. One immunization, however, failed to protect HLA-A2.1 transgenic Rabbits against viral DNA infection. This study further demonstrated that the HLA-A2.1 transgenic Rabbits can be used to test the immunogenicity of HLA-A2.1 restricted epitopes identified by MHCI epitope predication software.
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CRPV Genomes with Synonymous Codon Optimizations in the CRPV E7 Gene Show Phenotypic Differences in Growth and Altered Immunity upon E7 Vaccination
2008Co-Authors: Nancy M Cladel, Karla K. Balogh, Neil D ChristensenAbstract:Papillomaviruses use rare codons relative to their hosts. Recent studies have demonstrated that synonymous codon changes in viral genes can lead to increased protein production when the codons are matched to those of cells in which the protein is being expressed. We theorized that the immunogenicity of the virus would be enhanced by matching codons of selected viral genes to those of the host. We report here that synonymous codon changes in the E7 oncogene are tolerated in the context of the Cottontail Rabbit Papillomavirus (CRPV) genome. Papilloma growth rates differ depending upon the changes made indicating that synonymous codons are not necessarily neutral. Immunization with wild type E7 DNA yielded significant protection from subsequent challenge by both wild type and codon-modified genomes. The reduction in growt
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CRPV genomes with synonymous codon optimizations in the CRPV E7 gene show phenotypic differences in growth and altered immunity upon E7 vaccination.
Public Library of Science (PLoS), 2008Co-Authors: Nancy M Cladel, Karla K. Balogh, Neil D ChristensenAbstract:Papillomaviruses use rare codons relative to their hosts. Recent studies have demonstrated that synonymous codon changes in viral genes can lead to increased protein production when the codons are matched to those of cells in which the protein is being expressed. We theorized that the immunogenicity of the virus would be enhanced by matching codons of selected viral genes to those of the host. We report here that synonymous codon changes in the E7 oncogene are tolerated in the context of the Cottontail Rabbit Papillomavirus (CRPV) genome. Papilloma growth rates differ depending upon the changes made indicating that synonymous codons are not necessarily neutral. Immunization with wild type E7 DNA yielded significant protection from subsequent challenge by both wild type and codon-modified genomes. The reduction in growth was most dramatic with the genome containing the greatest number of synonymous codon changes
Xuwen Peng - One of the best experts on this subject based on the ideXlab platform.
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Long-peptide therapeutic vaccination against CRPV-induced papillomas in HLA-A2.1 transgenic Rabbits
Elsevier, 2014Co-Authors: Lynn R. Budgeon, Nancy M Cladel, Xuwen Peng, Karla K. Balogh, Neil D ChristensenAbstract:Long peptide immunization is a promising strategy to clear established tumors. In the current study, we investigated the therapeutic effect of a naturally existing long peptide that contained two HLA-A2.1 restricted epitopes (CRPVE1/149–157 and CRPVE1/161–169) from Cottontail Rabbit Papillomavirus (CRPV) E1 using our CRPV/HLA-A2.1 transgenic Rabbit model. A universal Tetanus Toxin helper motif (TT helper) was tagged at either the N-terminus or the carboxyl-terminus of this long peptide and designated as TT-E1 peptide and E1 peptide-TT, respectively. Four groups of HLA-A2.1 transgenic Rabbits were infected with wild type CRPV DNA. Three weeks post-infection, the Rabbits were immunized four times with TT-E1 peptide, E1 peptide only, E1 peptide-TT or TT-control peptide with two-week intervals between immunizations. Tumor outgrowth was monitored and recorded weekly. After the third booster immunization, tumors on two of the four E1 peptide-TT immunized Rabbits began to shrink. One animal from this group was free of tumors at the termination of the study. The mean papilloma size of E1 peptide-TT immunized Rabbits was significantly smaller when compared with that of the three other groups (P
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protective immunity with an e1 multivalent epitope dna vaccine against Cottontail Rabbit Papillomavirus crpv infection in an hla a2 1 transgenic Rabbit model
Vaccine, 2008Co-Authors: Nancy M Cladel, Xuwen Peng, Karla K. Balogh, Neil D ChristensenAbstract:Cottontail Rabbit Papillomavirus (CRPV)/Rabbit model is widely used to study pathogenesis of Papillomavirus infections and malignant tumor progression. Recently, we established HLA-A2.1 transgenic Rabbit lines and demonstrated efficacy for the testing of immunogenicity of a well-known A2-resticted epitope (HPV16E7/82-90) [Hu J, Peng X, Schell TD, Budgeon LR, Cladel NM, Christensen ND. An HLA-A2.1-transgenic Rabbit model to study immunity to Papillomavirus infection. J Immunol 2006;177(11):8037-45]. In the present study, we screened five HLA-A2.1 restricted epitopes from CRPVE1 (selected using online MHCI epitope prediction software) and constructed a multivalent epitope DNA vaccine (CRPVE1ep1-5). CRPVE1ep1-5 and a control DNA vaccine (Ub3) were then delivered intracutaneously onto normal and HLA-A2.1 transgenic Rabbits, respectively, by a helium-driven gene-gun delivery system. One, two or three immunizations were given to different groups of animals from both New Zealand White outbred and EIII/JC inbred genetic background. Two and three immunizations with CRPVE1ep1-5 DNA vaccine provided complete protection against viral DNA infection of HLA-A2.1 transgenic Rabbits from both genetic backgrounds but not in the control-vaccinated groups. One immunization, however, failed to protect HLA-A2.1 transgenic Rabbits against viral DNA infection. This study further demonstrated that the HLA-A2.1 transgenic Rabbits can be used to test the immunogenicity of HLA-A2.1 restricted epitopes identified by MHCI epitope predication software.
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establishment of a Cottontail Rabbit Papillomavirus hla a2 1 transgenic Rabbit model
Journal of Virology, 2007Co-Authors: Xuwen Peng, Nancy M Cladel, Lynn R. Budgeon, Karla K. Balogh, Neil D ChristensenAbstract:Three transgenic Rabbit lines that express a well-characterized human major histocompatibility complex class I (MHC-I) gene (HLA-A2.1) have been established. All three lines carry the HLA-A2.1 heavy chain and are able to pass the transgene to their offspring with both the outbred and the inbred EIII/JC genetic background. HLA-A2.1 colocalizes exclusively with Rabbit MHC-I on the cell surfaces. These HLA-A2.1 transgenic Rabbits demonstrated infection patterns similar to those found after Cottontail Rabbit Papillomavirus (CRPV) challenge when compared with results in normal Rabbits, although higher regression rates were found in HLA-A2.1 transgenic Rabbits. Because the CRPV genome can accommodate significant modifications, the CRPV/HLA-A2.1 Rabbit model has the potential to be used to screen HLA-A2.1-restricted immunogenic epitopes from human Papillomaviruses in the context of in vivo Papillomavirus infection.
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Establishment of a Cottontail Rabbit Papillomavirus/HLA-A2.1 Transgenic Rabbit Model
Journal of Virology, 2007Co-Authors: Xuwen Peng, Nancy M Cladel, Lynn R. Budgeon, Karla K. Balogh, Neil D ChristensenAbstract:Three transgenic Rabbit lines that express a well-characterized human major histocompatibility complex class I (MHC-I) gene (HLA-A2.1) have been established. All three lines carry the HLA-A2.1 heavy chain and are able to pass the transgene to their offspring with both the outbred and the inbred EIII/JC genetic background. HLA-A2.1 colocalizes exclusively with Rabbit MHC-I on the cell surfaces. These HLA-A2.1 transgenic Rabbits demonstrated infection patterns similar to those found after Cottontail Rabbit Papillomavirus (CRPV) challenge when compared with results in normal Rabbits, although higher regression rates were found in HLA-A2.1 transgenic Rabbits. Because the CRPV genome can accommodate significant modifications, the CRPV/HLA-A2.1 Rabbit model has the potential to be used to screen HLA-A2.1-restricted immunogenic epitopes from human Papillomaviruses in the context of in vivo Papillomavirus infection.
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an hla a2 1 transgenic Rabbit model to study immunity to Papillomavirus infection
Journal of Immunology, 2006Co-Authors: Xuwen Peng, Nancy M Cladel, Lynn R. Budgeon, Todd D Schell, Neil D ChristensenAbstract:We have established several HLA-A2.1-transgenic Rabbit lines to provide a host to study CD8(+) T cell responses during virus infections. HLA-A2.1 protein expression was detected on cell surfaces within various organ tissues. Continuous cultured cells from these transgenic Rabbits were capable of presenting both endogenous and exogenous HLA-A2.1-restricted epitopes to an HLA-A2.1-restricted epitope-specific CTL clone. A DNA vaccine containing an HLA-A2.1-restricted human Papillomavirus type 16 E7 epitope (amino acid residues 82-90) stimulated epitope-specific CTLs in both PBLs and spleen cells of transgenic Rabbits. In addition, vaccinated transgenic Rabbits were protected against infection with a mutant Cottontail Rabbit Papillomavirus DNA containing an embedded human Papillomavirus type 16 E7/82-90 epitope. Complete protection was achieved using a multivalent epitope DNA vaccine based on epitope selection from Cottontail Rabbit Papillomavirus E1 using MHC class I epitope prediction software. HLA-A2.1-transgenic Rabbits will be an important preclinical animal model system to study virus-host interactions and to assess specific targets for immunotherapy.
Nancy M Cladel - One of the best experts on this subject based on the ideXlab platform.
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Long-peptide therapeutic vaccination against CRPV-induced papillomas in HLA-A2.1 transgenic Rabbits
Elsevier, 2014Co-Authors: Lynn R. Budgeon, Nancy M Cladel, Xuwen Peng, Karla K. Balogh, Neil D ChristensenAbstract:Long peptide immunization is a promising strategy to clear established tumors. In the current study, we investigated the therapeutic effect of a naturally existing long peptide that contained two HLA-A2.1 restricted epitopes (CRPVE1/149–157 and CRPVE1/161–169) from Cottontail Rabbit Papillomavirus (CRPV) E1 using our CRPV/HLA-A2.1 transgenic Rabbit model. A universal Tetanus Toxin helper motif (TT helper) was tagged at either the N-terminus or the carboxyl-terminus of this long peptide and designated as TT-E1 peptide and E1 peptide-TT, respectively. Four groups of HLA-A2.1 transgenic Rabbits were infected with wild type CRPV DNA. Three weeks post-infection, the Rabbits were immunized four times with TT-E1 peptide, E1 peptide only, E1 peptide-TT or TT-control peptide with two-week intervals between immunizations. Tumor outgrowth was monitored and recorded weekly. After the third booster immunization, tumors on two of the four E1 peptide-TT immunized Rabbits began to shrink. One animal from this group was free of tumors at the termination of the study. The mean papilloma size of E1 peptide-TT immunized Rabbits was significantly smaller when compared with that of the three other groups (P
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protective immunity with an e1 multivalent epitope dna vaccine against Cottontail Rabbit Papillomavirus crpv infection in an hla a2 1 transgenic Rabbit model
Vaccine, 2008Co-Authors: Nancy M Cladel, Xuwen Peng, Karla K. Balogh, Neil D ChristensenAbstract:Cottontail Rabbit Papillomavirus (CRPV)/Rabbit model is widely used to study pathogenesis of Papillomavirus infections and malignant tumor progression. Recently, we established HLA-A2.1 transgenic Rabbit lines and demonstrated efficacy for the testing of immunogenicity of a well-known A2-resticted epitope (HPV16E7/82-90) [Hu J, Peng X, Schell TD, Budgeon LR, Cladel NM, Christensen ND. An HLA-A2.1-transgenic Rabbit model to study immunity to Papillomavirus infection. J Immunol 2006;177(11):8037-45]. In the present study, we screened five HLA-A2.1 restricted epitopes from CRPVE1 (selected using online MHCI epitope prediction software) and constructed a multivalent epitope DNA vaccine (CRPVE1ep1-5). CRPVE1ep1-5 and a control DNA vaccine (Ub3) were then delivered intracutaneously onto normal and HLA-A2.1 transgenic Rabbits, respectively, by a helium-driven gene-gun delivery system. One, two or three immunizations were given to different groups of animals from both New Zealand White outbred and EIII/JC inbred genetic background. Two and three immunizations with CRPVE1ep1-5 DNA vaccine provided complete protection against viral DNA infection of HLA-A2.1 transgenic Rabbits from both genetic backgrounds but not in the control-vaccinated groups. One immunization, however, failed to protect HLA-A2.1 transgenic Rabbits against viral DNA infection. This study further demonstrated that the HLA-A2.1 transgenic Rabbits can be used to test the immunogenicity of HLA-A2.1 restricted epitopes identified by MHCI epitope predication software.
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CRPV Genomes with Synonymous Codon Optimizations in the CRPV E7 Gene Show Phenotypic Differences in Growth and Altered Immunity upon E7 Vaccination
2008Co-Authors: Nancy M Cladel, Karla K. Balogh, Neil D ChristensenAbstract:Papillomaviruses use rare codons relative to their hosts. Recent studies have demonstrated that synonymous codon changes in viral genes can lead to increased protein production when the codons are matched to those of cells in which the protein is being expressed. We theorized that the immunogenicity of the virus would be enhanced by matching codons of selected viral genes to those of the host. We report here that synonymous codon changes in the E7 oncogene are tolerated in the context of the Cottontail Rabbit Papillomavirus (CRPV) genome. Papilloma growth rates differ depending upon the changes made indicating that synonymous codons are not necessarily neutral. Immunization with wild type E7 DNA yielded significant protection from subsequent challenge by both wild type and codon-modified genomes. The reduction in growt
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CRPV genomes with synonymous codon optimizations in the CRPV E7 gene show phenotypic differences in growth and altered immunity upon E7 vaccination.
Public Library of Science (PLoS), 2008Co-Authors: Nancy M Cladel, Karla K. Balogh, Neil D ChristensenAbstract:Papillomaviruses use rare codons relative to their hosts. Recent studies have demonstrated that synonymous codon changes in viral genes can lead to increased protein production when the codons are matched to those of cells in which the protein is being expressed. We theorized that the immunogenicity of the virus would be enhanced by matching codons of selected viral genes to those of the host. We report here that synonymous codon changes in the E7 oncogene are tolerated in the context of the Cottontail Rabbit Papillomavirus (CRPV) genome. Papilloma growth rates differ depending upon the changes made indicating that synonymous codons are not necessarily neutral. Immunization with wild type E7 DNA yielded significant protection from subsequent challenge by both wild type and codon-modified genomes. The reduction in growth was most dramatic with the genome containing the greatest number of synonymous codon changes
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establishment of a Cottontail Rabbit Papillomavirus hla a2 1 transgenic Rabbit model
Journal of Virology, 2007Co-Authors: Xuwen Peng, Nancy M Cladel, Lynn R. Budgeon, Karla K. Balogh, Neil D ChristensenAbstract:Three transgenic Rabbit lines that express a well-characterized human major histocompatibility complex class I (MHC-I) gene (HLA-A2.1) have been established. All three lines carry the HLA-A2.1 heavy chain and are able to pass the transgene to their offspring with both the outbred and the inbred EIII/JC genetic background. HLA-A2.1 colocalizes exclusively with Rabbit MHC-I on the cell surfaces. These HLA-A2.1 transgenic Rabbits demonstrated infection patterns similar to those found after Cottontail Rabbit Papillomavirus (CRPV) challenge when compared with results in normal Rabbits, although higher regression rates were found in HLA-A2.1 transgenic Rabbits. Because the CRPV genome can accommodate significant modifications, the CRPV/HLA-A2.1 Rabbit model has the potential to be used to screen HLA-A2.1-restricted immunogenic epitopes from human Papillomaviruses in the context of in vivo Papillomavirus infection.
Lynn R. Budgeon - One of the best experts on this subject based on the ideXlab platform.
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Long-peptide therapeutic vaccination against CRPV-induced papillomas in HLA-A2.1 transgenic Rabbits
Elsevier, 2014Co-Authors: Lynn R. Budgeon, Nancy M Cladel, Xuwen Peng, Karla K. Balogh, Neil D ChristensenAbstract:Long peptide immunization is a promising strategy to clear established tumors. In the current study, we investigated the therapeutic effect of a naturally existing long peptide that contained two HLA-A2.1 restricted epitopes (CRPVE1/149–157 and CRPVE1/161–169) from Cottontail Rabbit Papillomavirus (CRPV) E1 using our CRPV/HLA-A2.1 transgenic Rabbit model. A universal Tetanus Toxin helper motif (TT helper) was tagged at either the N-terminus or the carboxyl-terminus of this long peptide and designated as TT-E1 peptide and E1 peptide-TT, respectively. Four groups of HLA-A2.1 transgenic Rabbits were infected with wild type CRPV DNA. Three weeks post-infection, the Rabbits were immunized four times with TT-E1 peptide, E1 peptide only, E1 peptide-TT or TT-control peptide with two-week intervals between immunizations. Tumor outgrowth was monitored and recorded weekly. After the third booster immunization, tumors on two of the four E1 peptide-TT immunized Rabbits began to shrink. One animal from this group was free of tumors at the termination of the study. The mean papilloma size of E1 peptide-TT immunized Rabbits was significantly smaller when compared with that of the three other groups (P
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establishment of a Cottontail Rabbit Papillomavirus hla a2 1 transgenic Rabbit model
Journal of Virology, 2007Co-Authors: Xuwen Peng, Nancy M Cladel, Lynn R. Budgeon, Karla K. Balogh, Neil D ChristensenAbstract:Three transgenic Rabbit lines that express a well-characterized human major histocompatibility complex class I (MHC-I) gene (HLA-A2.1) have been established. All three lines carry the HLA-A2.1 heavy chain and are able to pass the transgene to their offspring with both the outbred and the inbred EIII/JC genetic background. HLA-A2.1 colocalizes exclusively with Rabbit MHC-I on the cell surfaces. These HLA-A2.1 transgenic Rabbits demonstrated infection patterns similar to those found after Cottontail Rabbit Papillomavirus (CRPV) challenge when compared with results in normal Rabbits, although higher regression rates were found in HLA-A2.1 transgenic Rabbits. Because the CRPV genome can accommodate significant modifications, the CRPV/HLA-A2.1 Rabbit model has the potential to be used to screen HLA-A2.1-restricted immunogenic epitopes from human Papillomaviruses in the context of in vivo Papillomavirus infection.
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Establishment of a Cottontail Rabbit Papillomavirus/HLA-A2.1 Transgenic Rabbit Model
Journal of Virology, 2007Co-Authors: Xuwen Peng, Nancy M Cladel, Lynn R. Budgeon, Karla K. Balogh, Neil D ChristensenAbstract:Three transgenic Rabbit lines that express a well-characterized human major histocompatibility complex class I (MHC-I) gene (HLA-A2.1) have been established. All three lines carry the HLA-A2.1 heavy chain and are able to pass the transgene to their offspring with both the outbred and the inbred EIII/JC genetic background. HLA-A2.1 colocalizes exclusively with Rabbit MHC-I on the cell surfaces. These HLA-A2.1 transgenic Rabbits demonstrated infection patterns similar to those found after Cottontail Rabbit Papillomavirus (CRPV) challenge when compared with results in normal Rabbits, although higher regression rates were found in HLA-A2.1 transgenic Rabbits. Because the CRPV genome can accommodate significant modifications, the CRPV/HLA-A2.1 Rabbit model has the potential to be used to screen HLA-A2.1-restricted immunogenic epitopes from human Papillomaviruses in the context of in vivo Papillomavirus infection.
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an hla a2 1 transgenic Rabbit model to study immunity to Papillomavirus infection
Journal of Immunology, 2006Co-Authors: Xuwen Peng, Nancy M Cladel, Lynn R. Budgeon, Todd D Schell, Neil D ChristensenAbstract:We have established several HLA-A2.1-transgenic Rabbit lines to provide a host to study CD8(+) T cell responses during virus infections. HLA-A2.1 protein expression was detected on cell surfaces within various organ tissues. Continuous cultured cells from these transgenic Rabbits were capable of presenting both endogenous and exogenous HLA-A2.1-restricted epitopes to an HLA-A2.1-restricted epitope-specific CTL clone. A DNA vaccine containing an HLA-A2.1-restricted human Papillomavirus type 16 E7 epitope (amino acid residues 82-90) stimulated epitope-specific CTLs in both PBLs and spleen cells of transgenic Rabbits. In addition, vaccinated transgenic Rabbits were protected against infection with a mutant Cottontail Rabbit Papillomavirus DNA containing an embedded human Papillomavirus type 16 E7/82-90 epitope. Complete protection was achieved using a multivalent epitope DNA vaccine based on epitope selection from Cottontail Rabbit Papillomavirus E1 using MHC class I epitope prediction software. HLA-A2.1-transgenic Rabbits will be an important preclinical animal model system to study virus-host interactions and to assess specific targets for immunotherapy.
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protective cell mediated immunity by dna vaccination against Papillomavirus l1 capsid protein in the Cottontail Rabbit Papillomavirus model
Viral Immunology, 2006Co-Authors: Nancy M Cladel, Martin D. Pickel, Cynthia A Reed, Lynn R. Budgeon, Neil D ChristensenAbstract:Papillomavirus major capsid protein L1 has successfully stimulated protective immunity against virus infection by induction of neutralizing antibodies in animal models and in clinical trials. However, the potential impact of L1-induced protective cell-mediated immune (CMI) responses is difficult to measure in vivo because of the coincidence of anti-L1 antibody. In this study, we tested the hypothesis that L1 could activate CMI, using the Cottontail Rabbit Papillomavirus (CRPV)–Rabbit model. A unique property of this model is that infections can be initiated with viral DNA, thus bypassing all contributions to protection via neutralizing anti-L1 antibody. DNA vaccines containing either CRPV L1, or subfragments of L1 (amino-terminal two-thirds of L1 [L1N] and the carboxylterminal two-thirds of L1 [L1C]), were delivered intracutaneously into Rabbits, using a gene gun. After three booster immunizations, the Rabbits were challenged with several viral DNA constructs: wild-type CRPV, CRPV L1ATGko (an L1 ATG knock...
Ricai Han - One of the best experts on this subject based on the ideXlab platform.
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gene gun mediated intracutaneous vaccination with Papillomavirus e7 gene delays cancer development of Papillomavirus induced skin papillomas on Rabbits
Cancer Detection and Prevention, 2002Co-Authors: Ricai Han, Martin D. Pickel, Cynthia A Reed, Nancy M Cladel, Xuwen Peng, Lynn R. Budgeon, Neil D ChristensenAbstract:Abstract High-risk human Papillomavirus (HPV) E6 and E7 viral oncogenes are expressed in HPV-associated cancers, and thus represent tumor-specific antigens. We used the Cottontail Rabbit Papillomavirus (CRPV) Rabbit model to test whether vaccination with either the E6 or E7 genes alone could prevent or delay carcinoma development. CRPV-induced papillomas on 24 Rabbits were allowed to grow for 3 months without any treatment intervention. An immunization protocol using gene gun-mediated intracutaneous administration of DNA plasmids encoding the E6 or the E7 gene or vector only, respectively was initiated at this time point. Carcinoma development was followed up to 24 months after virus infection. Within this period, five Rabbits died due to other causes but without carcinoma; one from the vector control group, and two each from the E6- and E7-vaccinated groups. The remaining seven Rabbits from the vector control group developed carcinoma within 7–17 months. The remaining six E6-vaccinated Rabbits developed cancer within 8–15 months. There was no delay in cancer development for the E6-vaccinated Rabbits compared to the vector-injected Rabbits. Some delay in cancer development in the remaining E7-vaccinated Rabbits was observed; one developed cancer at month 23 and a second was without cancer at month 24. In addition, some E7-vaccinated Rabbits with primary skin carcinomas had fewer lung metastases (
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intracutaneous dna vaccination with the e8 gene of Cottontail Rabbit Papillomavirus induces protective immunity against virus challenge in Rabbits
Journal of Virology, 2002Co-Authors: Ricai Han, Martin D. Pickel, Nancy M Cladel, Neil D ChristensenAbstract:The Cottontail Rabbit Papillomavirus (CRPV)-Rabbit model has been used in several studies for testing prophylactic and therapeutic Papillomavirus vaccines. Earlier observations had shown that the CRPV nonstructural genes E1, E2, and E6 induced strong to partial protective immunity against CRPV infection. In this study, we found that CRPV E8 immunization eliminated virus-induced papillomas in EIII/JC inbred Rabbits (100%) and provided partial protection (55%) against virus challenge in outbred New Zealand White Rabbits. CRPV-E8 is a small open reading frame, coding for a 50-amino-acid protein, that is colinear with the CRPV E6 gene and has features similar to those of the bovine Papillomavirus and human Papillomavirus E5 genes. Papillomas that grew on E8-vaccinated outbred Rabbits were significantly smaller than those on vector-vaccinated Rabbits (P < 0.01; t test). Delayed-type hypersensitivity skin tests showed that some of the E8-vaccinated Rabbits had positive responses to E8-specific peptides.
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DNA Vaccination Prevents and/or Delays Carcinoma Development of Papillomavirus-Induced Skin Papillomas on Rabbits
Journal of virology, 2000Co-Authors: Ricai Han, Martin D. Pickel, Cynthia A Reed, Nancy M Cladel, Xuwen Peng, Lynn R. Budgeon, Neil D ChristensenAbstract:Malignant progression is a life-threatening consequence of human Papillomavirus-associated lesions. In this study, we tested the efficacy of Papillomavirus early-gene-based vaccines for prevention of carcinoma development of Papillomavirus-induced skin papillomas on Rabbits. Rabbit skin papillomas were initiated by infection with Cottontail Rabbit Papillomavirus (CRPV). The papillomas were allowed to grow for 3 months without any treatment intervention. Rabbits were then immunized by gene gun-mediated intracutaneous administration of four DNA plasmids encoding CRPV E1, E2, E6, and E7 genes, respectively. All eight control Rabbits receiving vector alone developed invasive carcinoma within 8 to 13 months. In contrast, only two of eight vaccinated Rabbits developed carcinoma at 12 and 15 months, respectively. Papilloma growth was suppressed in the majority of vaccinated Rabbits but not completely eradicated. These results indicate that gene gun-mediated immunization with Papillomavirus early genes may be a promising strategy for prevention of malignant progression of human Papillomavirus-associated lesions in humans.
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immunization of Rabbits with Cottontail Rabbit Papillomavirus e1 and e2 genes protective immunity induced by gene gun mediated intracutaneous delivery but not by intramuscular injection
Vaccine, 2000Co-Authors: Ricai Han, Cynthia A Reed, Nancy M Cladel, Neil D ChristensenAbstract:We previously demonstrated that gene gun-based intracutaneous vaccination of Rabbits with a combination of, but not with individual Papillomavirus E1, E2, E6 and E7 genes provided complete protection against Cottontail Rabbit Papillomavirus (CRPV) infection. In the present study, we tested whether vaccination of inbred and outbred Rabbits with a combination of CRPV E1 and E2 genes could provide complete protection against virus infection. In the first experiment, gene gun-based intracutaneous vaccination with E1 and E2 genes prevented papilloma formation in the majority of inbred Rabbits and promoted systemic papilloma regression in one non-protected Rabbit. In contrast, needle-mediated intramuscular injection of E1 and E2 genes did not prevent papilloma formation nor promoted systemic papilloma regression, indicating an absence of strong protective immunity. In the second experiment, six outbred Rabbits were immunized by gene gun-based intracutaneous administration of the E1 and E2 genes. Prevention of papilloma formation or systemic papilloma regression was observed in three vaccinated Rabbits. Papillomas persisted on the remaining three Rabbits, but were significantly smaller than that on control Rabbits. These results suggested that gene gun-based intracutaneous vaccination with the combination of Papillomavirus E1 and E2 genes induced strong protective antivirus immunity but may be insufficient for complete protection in an outbred population.
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protection of Rabbits from viral challenge by gene gun based intracutaneous vaccination with a combination of Cottontail Rabbit Papillomavirus e1 e2 e6 and e7 genes
Journal of Virology, 1999Co-Authors: Ricai Han, Cynthia A Reed, Nancy M Cladel, Xuwen Peng, Neil D ChristensenAbstract:In this study, Cottontail Rabbit Papillomavirus infection of domestic Rabbits was used as an animal model to develop Papillomavirus early gene-based vaccines. Groups of Rabbits were intracutaneously vaccinated with single Papillomavirus early genes E1, E2, E6, and E7 or with a combination of these four genes. Only a fraction of Rabbits were protected from subsequent viral challenge when vaccinated with the E1 or E6 gene. Viral tumor growth in those Rabbits vaccinated with the E1 or E2 gene was suppressed compared to that in controls. In contrast, seven of nine Rabbits vaccinated with the combination of the E1, E2, E6, and E7 genes were completely protected against viral challenge. These data indicated that intracutaneous genetic vaccination with the combination of the E1, E2, E6, and E7 genes can be an effective strategy for immunoprophylaxis of Papillomavirus infection.
