Development of a replication-deficient adenoviral vector-based vaccine candidate for the interception of HPV16- and HPV18-induced infections and disease.
| Title: | Development of a replication-deficient adenoviral vector-based vaccine candidate for the interception of HPV16- and HPV18-induced infections and disease. |
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| Authors: | Khan S; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Oosterhuis K; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Wunderlich K; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Bunnik EM; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Bhaggoe M; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Boedhoe S; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Karia S; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Steenbergen RDM; Department of Pathology, VU University Medical Center Amsterdam, The Netherlands.; Bosch L; Department of Pathology, VU University Medical Center Amsterdam, The Netherlands.; Serroyen J; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Janssen S; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Schuitemaker H; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Vellinga J; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Scheper G; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Zahn R; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands.; Custers J; Janssen Vaccines and Preventions BV, CA, Leiden, The Netherlands. |
| Source: | International journal of cancer [Int J Cancer] 2017 Jul 15; Vol. 141 (2), pp. 393-404. Date of Electronic Publication: 2017 Apr 24. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0042124 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0215 (Electronic) Linking ISSN: 00207136 NLM ISO Abbreviation: Int J Cancer Subsets: MEDLINE |
| Imprint Name(s): | Publication: 1995- : New York, NY : Wiley-Liss; Original Publication: 1966-1984 : Genève : International Union Against Cancer |
| MeSH Terms: | Dependovirus/*physiology ; Human papillomavirus 16/*immunology ; Human papillomavirus 18/*immunology ; Papillomavirus Infections/*therapy ; Uterine Cervical Neoplasms/*therapy; Antigens, Viral, Tumor/immunology ; Papillomavirus Vaccines/immunology ; Uterine Cervical Neoplasms/virology ; Animals ; Female ; Humans ; Mice ; NIH 3T3 Cells ; Virus Replication ; Xenograft Model Antitumor Assays |
| Abstract: | High-risk Human papilloma virus (HPV) types are the causative agents of cervical cancer and several other anogenital malignancies. The viral proteins expressed in the (pre)malignant cells are considered ideal targets for immunological intervention. Many approaches have been evaluated for this purpose, mostly aiming at the induction of HPV16 E7- and/or E6-specific cellular immunogenicity. As clinical success has so far been limited, novel approaches are required. We describe the development and pre-clinical testing of a vaccine candidate consisting of replication-deficient adenovirus type 26 and 35 based vectors for the interception of HPV16- and HPV18-related disease. We developed HPV16- and HPV18-specific antigens consisting of fusion proteins of E2, E6 and E7. The vaccine will be suitable for every disease stage, from incident and persistent infections where E2 is predominantly expressed up to late stages where E6 and E7 expression are upregulated. Importantly E6 and E7 are present as reordered fragments to abrogate the transforming activity of these two proteins. Loss of transforming activity was demonstrated in different in vitro models. Robust T-cell immunogenicity was induced upon immunization of mice with the vaccine candidate. Finally, the developed vaccine vectors showed considerable therapeutic efficacy in the TC-1 mouse model. The absence of transforming activity of the antigens and the favorable immunogenicity profile of the adenovirus based vectors along with the fact that these vectors can be readily produced on a large scale makes this approach attractive for clinical evaluation.; (© 2017 UICC.) |
| Contributed Indexing: | Keywords: HPV; adenovirus vector; therapeutic vaccine |
| Substance Nomenclature: | 0 (Antigens, Viral, Tumor); 0 (Papillomavirus Vaccines) |
| Entry Date(s): | Date Created: 20170307 Date Completed: 20170914 Latest Revision: 20180130 |
| Update Code: | 20260130 |
| DOI: | 10.1002/ijc.30679 |
| PMID: | 28263390 |
| Database: | MEDLINE |
Journal Article