Therapeutic vaccination of rabbits with a ubiquitin-fused papillomavirus E1, E2, E6 and E7 DNA vaccine

Brandsma, Janet L.; Shlyankevich, Mark; Zelterman, Daniel; Su, Yongxuan

doi:10.1016/j.vaccine.2007.06.012

Cited by 28 publications

(23 citation statements)

References 24 publications

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“…However, E1 immunization has been reported to induce strongly protective immunity and/or papilloma regression [41-44]. E1 has also been tested for therapeutic purposes in previous studies [33, 45-47]. Our study further confirmed that a therapeutic effect could be achieved by E1 targeted immunization for early stage papillomas in rabbits.…”

Section: Discussionsupporting

confidence: 83%

Using HLA-A2.1 Transgenic Rabbit Model to Screen and Characterize New HLA-A2.1 Restricted Epitope DNA Vaccines

Hu¹,

Schell

Peng³

et al. 2010

J Vaccin Vaccinat

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Section: Discussionsupporting

confidence: 83%

Using HLA-A2.1 Transgenic Rabbit Model to Screen and Characterize New HLA-A2.1 Restricted Epitope DNA Vaccines

Hu¹,

Schell

Peng³

et al. 2010

J Vaccin Vaccinat

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“…Improved preventive and therapeutic endpoints have been found in previous studies using combinations of topical treatments and DNA vaccination [45], peptide and DNA vaccines [42], DNA vaccines based on recombinant VSV [44,46] and combinations of multiple antigens [26,35,47]. Adjuvants such as Toll-like receptor agonists and CpG have been included in tumor therapeutic studies to enhance the specific adaptive immunity in hosts [48,49].…”

Section: Discussionmentioning

confidence: 99%

Long-peptide therapeutic vaccination against CRPV-induced papillomas in HLA-A2.1 transgenic rabbits

Budgeon

Balogh

et al. 2014

Trials in Vaccinology

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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, E1peptide 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<0.05, one way ANOVA analysis). It is interesting that E1 peptide-TT vaccination not only stimulated stronger T cell mediate immune responses but also stronger antibody generations. We conclude that the location of a TT helper motif tagged at the long peptide vaccine is critical for the outcome of therapeutic responses to persistent tumors in our HLA-A2.1 transgenic rabbit model.

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“…Given the high immunogenicity, E2 may be considered a target to defeat viral infection in the early or even late stages of disease. A therapeutic vaccine might be effective by inducing E2-specific cytotoxic T cells, as has been tested in the cottontail rabbit PV model by antagonizing experimentally induced viral tumours (Leachman et al, 2002;Brandsma et al, 2007).Further insights into the initial virus infection and tumour progression were obtained by our prospective study, in which L1 and E2 seroreactivity correlated with the outcome of disease. The E2 response was detectable shortly after birth, and it seems that these antibodies mark the early stages of infection.…”

mentioning

confidence: 89%

Section: Analysis Of the Serological Response Against Mnpv Andmentioning

confidence: 99%

Serological markers for papillomavirus infection and skin tumour development in the rodent model Mastomys coucha

Schäfer

Neumann

Waterboer

et al. 2010

Journal of General Virology

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This study used the rodent Mastomys coucha latently infected with Mastomys natalensis papillomavirus (MnPV) and Mastomys coucha PV2 (McPV2), which induce skin papillomas and anogenital condylomas, respectively, to investigate PV antibody responses as serological markers during pathogenesis. In a case-control study (137 animals), virus and tumour prevalence correlated with the seroresponse against the early E2 and late L1 viral proteins. A prospective study (53 animals) revealed for the first time the course of these antibody responses during all stages of a natural PV infection. Numerous tumour entities were observed on the eyelid and in the oral cavity. DNA analyses indicated that McPV2 was not restricted to condylomas but was also present in these mucosa-associated papillomas. The serological survey using a recently established glutathione S-transferase-capture ELISA detected a strong correlation between MnPV L1-specific antibodies and the presence of papillomas on the skin, eye and ear (P,0.001). Notably, extensive antibody responses to MnPV E2 were also detected in these cases. A prospective study revealed that E2 reactivity occurred by the age of 1 month. MnPV L1 antibodies were found at 2.5 months, indicating the initiation of productive viral infection. Thirty-one out of 34 L1-seropositive animals at the age of 4.5 months developed MnPV-associated tumours (positive predictive value577 %), and none of the seronegative animals developed skin papillomas (negative predictive value5100 %). MnPV E2 and L1 serology thus provides a powerful tool for monitoring early infection and skin tumour progression in M. coucha. INTRODUCTIONPapillomaviruses (PVs) are small, non-enveloped DNA viruses that are frequently found in animals, particularly in vertebrates such as mammals and birds (Antonsson & Hansson, 2002). Different virus types infect epidermal or mucosal tissues and may cause diverse epithelial lesions such as papillomas and warts. PVs are represented by a large family of different genera, and specific types can induce cancerous lesions, for instance in rabbits, cattle and horses (Campo, 2002). An oncogenic potential has also been identified for human papillomaviruses (HPVs), which are by far the most heterogeneous group, with more than 100 types identified (de Villiers et al., 2004). Mucosal 'high-risk' HPV types have the potential to transform cells and are aetiologically linked to cancers, mostly in the uterine cervix (zur Hausen, 2002). Tumorigenicity and malignant progression are characterized by constitutive expression of the viral oncogenes E6/E7 and are often accompanied by integration of the viral DNA into the host genome. The oncogenic potential arises from their ability to interact with the cellular proliferation machinery, in particular the E6-induced degradation of p53 (Scheffner et al., 1993) and by E7 binding to pRB, releasing the S-phasepromoting factor E2F (Giarrè et al., 2001). During normal infection, the viruses replicate and mature in the course of epithelial differentiation, which is tightl...

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Therapeutic vaccination of rabbits with a ubiquitin-fused papillomavirus E1, E2, E6 and E7 DNA vaccine

Cited by 28 publications

References 24 publications

Using HLA-A2.1 Transgenic Rabbit Model to Screen and Characterize New HLA-A2.1 Restricted Epitope DNA Vaccines

Using HLA-A2.1 Transgenic Rabbit Model to Screen and Characterize New HLA-A2.1 Restricted Epitope DNA Vaccines

Long-peptide therapeutic vaccination against CRPV-induced papillomas in HLA-A2.1 transgenic rabbits

Serological markers for papillomavirus infection and skin tumour development in the rodent model Mastomys coucha

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