DNA Vaccination Prevents and/or Delays Carcinoma Development of Papillomavirus-Induced Skin Papillomas on Rabbits

Han, Ruiqin; Cladel, Nancy M.; Reed, Cynthia A.; Peng, Xuwen; Budgeon, Lynn R.; Pickel, M.; Christensen, Neil D.

doi:10.1128/jvi.74.20.9712-9716.2000

Cited by 53 publications

(34 citation statements)

References 33 publications

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“…As an example of the value of DNA-based therapeutic vaccines for HPV, Han et al (80) showed that intracutaneous immunisation of rabbits already displaying papillomas with four DNA plasmids encoding CRPV E1, E2, E6, and E7 genes, protected 75% of them from developing invasive carcinoma within 15 months. Liu et al (69) used a chimaeric gene containing a HPV-16 E7 cytotoxic T-lymphocyte (CTL) epitope DNA fused with a heat shock protein gene as a tumour vaccine delivered via an adeno-associated virus (AAV) recombinant.…”

Section: Dna Vaccinesmentioning

confidence: 99%

Human Papillomavirus (HPV) Infection in Southern Africa: Prevalence, Immunity, and Vaccine Prospects

et al. 2002

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SummaryHuman papillomavirus (HPV) associated cancers are more prevalent in developing countries compared to developed countries. The major cancer caused by HPV is cervical cancer. The humoral immune response to HPV can be a marker of past infection but may also reflect persistent infection and cervical disease. IgA antibodies to HPV in oral fluid were also found to be markers of cervical disease. Cell mediated immunity is important in clearing HPV infection and for regression of the associated lesions: this means that women infected with HIV have a high prevalence of co-infection with HPV. Good cervical screening programmes can control HPV associated cervical neoplasia. However, in countries such as South Africa, where these programmes are inadequate, there is a need for an HPV vaccine. The development of HPV vaccines is reviewed. There is a call for an inexpensive vaccine that will be accessible to the women that do not have access to adequate screening programmes and are therefore at the greatest risk of cervical cancer. IUBMB Life, 53: 253-258, 2002

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Section: Dna Vaccinesmentioning

confidence: 99%

Human Papillomavirus (HPV) Infection in Southern Africa: Prevalence, Immunity, and Vaccine Prospects

et al. 2002

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“…DNA vaccines 547 encoding a combination of viral early proteins may prove more effective than vaccines based on single genes. This is 548 suggested by recent work in the domestic rabbit (with CRPV challenge), in which DNA vaccination with a 549 combination of genes encoding E1, E2, E6 and E7 proved appeared more effective than DNA vaccines encoding only a 550 single protein (Han et al, 1999b). In Han's study, gene-gun vaccination did not elicit detectable humoral responses to 551 the encoded antigens, although T-cell lymphoproliferative responses were seen to each of the encoded antigens.…”

mentioning

confidence: 92%

“…In Han's study, gene-gun vaccination did not elicit detectable humoral responses to 551 the encoded antigens, although T-cell lymphoproliferative responses were seen to each of the encoded antigens. The 552 lack of humoral response to the encoded antigens was seen when DNA was delivered by either intracutaneous gene gun 553 (Han, et al, 1999b), or intramuscular injection (Han et al, 1999a). 554…”

mentioning

confidence: 99%

The immunology of animal papillomaviruses

Nicholls

Stanley

2000

Veterinary Immunology and Immunopathology

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13Papillomaviruses are species-and tissue-specific double-stranded DNA viruses. These viruses cause epithelial tumours 14 in many animals, including man. Typically, the benign warts undergo spontaneous, immune-mediated regression, most 15 likely effected by T cells (especially CD4, but also CD8 subsets), whereas humoral immunity can prevent new 16 infections. Some papillomavirus infections fail to regress spontaneously, and others progress to malignant epithelial 17 tumours. Additionally, the impact of these lesions is greater in immunosuppressed individuals. Many therapies are 18 ineffective, and there is much interest in the potential for immunological intervention in papillomavirus infections of 19 man and animals. Vaccination can be achieved with 'live' virus, formalin-inactivated virus, synthetic virus-like 20 particles, and DNA vaccination. There has been much recent progress in the development of such vaccines for 21 papillomavirus infections in the rabbit, ox and dog. Success in these animal models suggests that similar approaches 22 may prove useful for prophylactic or therapeutic vaccination against the important human papillomaviruses involved in 23 the development of cutaneous and anogenital warts, laryngeal papillomatosis, and cervical cancer. 24 25

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“…20 In the cottontail rabbit papillomavirus (CRPV) model, immunization of rabbits with DNA plasmid-encoding CRPV E2 prevented the development of skin papillomas. 21,22 These studies support the use of E2 as an immunologic target in vaccines for the protection or therapy of HPV infection and CIN. Thus virus-like particles composed of the viral capsid proteins (L1 and L2) for use in prophylaxis of HPV-associated disease have been modified to include E2 and E7 proteins.…”

mentioning

confidence: 65%

Human T cell responses to HPV 16 E2 generated with monocyte-derived dendritic cells

Davidson¹,

Brown²,

Burt³

et al. 2001

Int. J. Cancer

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Persistent infection with human papillomavirus (HPV) type 16 has been implicated in the etiology of cervical cancer. The E2 protein is required early in viral infection and therefore may serve as a useful immune target for a vaccine aimed at prevention or therapy of premalignant lesions. Dendritic cells (DC) prepared from monocytes and pulsed with bacterially produced HPV 16 E2 C-terminus protein were used to stimulate autologous T cells over several rounds of stimulation. T cells were tested for ␥-interferon release by ELISPOT and for cytotoxic activity by 51 chromium release assays. To generate E2-expressing target cells for cytotoxicity assays, we constructed a recombinant vaccinia virus encoding HPV 16 E2, which was used to infect autologous Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL). The results show that DC pulsed with E2 C-terminus protein induce ␥-interferon-releasing T cells as demonstrated by ELISPOT. Furthermore, we demonstrate E2-specific lysis of vaccinia-E2 infected autologous LCL by CD8؉ cytotoxic T lymphocytes (CTL). E2-specific CTL did not lyse untreated autologous LCL or LCL infected with wild-type vaccinia and showed low levels of cytotoxicity against natural killer cell-sensitive K562 cells. In addition, T cells stimulated with DC in the absence of E2 failed to demonstrate lysis of vaccinia-E2-labeled targets. Phenotypically, CTL populations were CD3؉/CD8؉. These results will facilitate the study of naturally occurring T-cell responses to HPV E2 in patients with cervical intraepithelial neoplasia and the development of immunotherapeutic strategies designed to treat this and other HPV-associated diseases. © 2001 Wiley-Liss, Inc. Key words: human papillomavirus (HPV); E2 protein; dendritic cells; cytotoxic T lymphocytes (CTL); ␥-interferon ELISPOT; primary immune responses; cervical intraepithelial neoplasia (CIN); cervical cancer; vaccinesPersistent infection with oncogenic human papillomaviruses (HPV) such as HPV 16 is necessary for the development of invasive cervical carcinoma. 1-4 Natural immunity plays an important role in the control of HPV infection, 5-7 and the identification of HPV-specific immunity in patients 8 -11 has provided the impetus for the development of vaccines to both prevent and treat HPVassociated disease. Most therapeutic vaccines have focused on stimulating specific cell-mediated immunity to HPV 16 E6 and E7 proteins, which are expressed in all stages of HPV-related disease development and are therefore appropriate immune targets in high grade and malignant disease. 12,13 Other early viral proteins could also be immune targets for vaccines aimed at treating HPV-associated disease. HPV 16 E2 is a 42-kDa protein comprising 3 functional domains: a 200-amino acid amino-terminal (N-terminal) activation domain 14 and a 100-amino acid carboxy-terminal (C-terminal) DNA-binding domain, 15 joined by a flexible hinge region. 16 E2 is necessary for viral replication 17,18 and for the transcriptional control of other viral proteins, including E6 and E7. 19 In c...

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DNA Vaccination Prevents and/or Delays Carcinoma Development of Papillomavirus-Induced Skin Papillomas on Rabbits

Cited by 53 publications

References 33 publications

Human Papillomavirus (HPV) Infection in Southern Africa: Prevalence, Immunity, and Vaccine Prospects

Human Papillomavirus (HPV) Infection in Southern Africa: Prevalence, Immunity, and Vaccine Prospects

The immunology of animal papillomaviruses

Human T cell responses to HPV 16 E2 generated with monocyte-derived dendritic cells

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