Development of a replication-deficient adenoviral vector-based vaccine candidate for the interception of HPV16- and HPV18-induced infections and disease

Selina Khan, Koen Oosterhuis, Kerstin Wunderlich, Evelien M. Bunnik, Melissa Bhaggoe, Satish Boedhoe, Santusha Karia, Renske D.M. Steenbergen, Leontien Bosch, Jan Serroyen, Sarah Janssen, Hanneke Schuitemaker, Jort Vellinga, Gert Scheper, Roland Zahn, Jerome Custers

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)393-404
Number of pages12
JournalInternational Journal of Cancer
Volume141
Issue number2
DOIs
Publication statusPublished - 15 Jul 2017

Cite this

Khan, Selina ; Oosterhuis, Koen ; Wunderlich, Kerstin ; Bunnik, Evelien M. ; Bhaggoe, Melissa ; Boedhoe, Satish ; Karia, Santusha ; Steenbergen, Renske D.M. ; Bosch, Leontien ; Serroyen, Jan ; Janssen, Sarah ; Schuitemaker, Hanneke ; Vellinga, Jort ; Scheper, Gert ; Zahn, Roland ; Custers, Jerome. / Development of a replication-deficient adenoviral vector-based vaccine candidate for the interception of HPV16- and HPV18-induced infections and disease. In: International Journal of Cancer. 2017 ; Vol. 141, No. 2. pp. 393-404.
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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.",
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author = "Selina Khan and Koen Oosterhuis and Kerstin Wunderlich and Bunnik, {Evelien M.} and Melissa Bhaggoe and Satish Boedhoe and Santusha Karia and Steenbergen, {Renske D.M.} and Leontien Bosch and Jan Serroyen and Sarah Janssen and Hanneke Schuitemaker and Jort Vellinga and Gert Scheper and Roland Zahn and Jerome Custers",
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Khan, S, Oosterhuis, K, Wunderlich, K, Bunnik, EM, Bhaggoe, M, Boedhoe, S, Karia, S, Steenbergen, RDM, Bosch, L, Serroyen, J, Janssen, S, Schuitemaker, H, Vellinga, J, Scheper, G, Zahn, R & Custers, J 2017, 'Development of a replication-deficient adenoviral vector-based vaccine candidate for the interception of HPV16- and HPV18-induced infections and disease' International Journal of Cancer, vol. 141, no. 2, pp. 393-404. https://doi.org/10.1002/ijc.30679

Development of a replication-deficient adenoviral vector-based vaccine candidate for the interception of HPV16- and HPV18-induced infections and disease. / Khan, Selina; Oosterhuis, Koen; Wunderlich, Kerstin; Bunnik, Evelien M.; Bhaggoe, Melissa; Boedhoe, Satish; Karia, Santusha; Steenbergen, Renske D.M.; Bosch, Leontien; Serroyen, Jan; Janssen, Sarah; Schuitemaker, Hanneke; Vellinga, Jort; Scheper, Gert; Zahn, Roland; Custers, Jerome.

In: International Journal of Cancer, Vol. 141, No. 2, 15.07.2017, p. 393-404.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Development of a replication-deficient adenoviral vector-based vaccine candidate for the interception of HPV16- and HPV18-induced infections and disease

AU - Khan, Selina

AU - Oosterhuis, Koen

AU - Wunderlich, Kerstin

AU - Bunnik, Evelien M.

AU - Bhaggoe, Melissa

AU - Boedhoe, Satish

AU - Karia, Santusha

AU - Steenbergen, Renske D.M.

AU - Bosch, Leontien

AU - Serroyen, Jan

AU - Janssen, Sarah

AU - Schuitemaker, Hanneke

AU - Vellinga, Jort

AU - Scheper, Gert

AU - Zahn, Roland

AU - Custers, Jerome

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