ΔE1 and high-capacity adenoviral vectors expressing full-length codon-optimized merozoite surface protein 1 for vaccination against Plasmodium falciparum

• Verfasst von: Zong, Shan [VerfasserIn]
• Verfasst von: Kron, Matthias W. [VerfasserIn]
• Verfasst von: Epp, Christian [VerfasserIn]
• Verfasst von: Engler, Tatjana [VerfasserIn]
• Verfasst von: Bujard, Hermann [VerfasserIn]
• Verfasst von: Kochanek, Stefan [VerfasserIn]
• Verfasst von: Kreppel, Florian [VerfasserIn]
• Titel: ΔE1 and high-capacity adenoviral vectors expressing full-length codon-optimized merozoite surface protein 1 for vaccination against Plasmodium falciparum
• Verf.angabe: Shan Zong, Matthias W. Kron, Christian Epp, Tatjana Engler, Hermann Bujard, Stefan Kochanek, Florian Kreppel
• E-Jahr: 2011
• Jahr: 22 December 2011
• Umfang: 10 S.
• Fussnoten: Gesehen am 23.01.2023
• Titel Quelle: Enthalten in: The journal of gene medicine
• Ort Quelle: New York, NY : Wiley Interscience, 1999
• Jahr Quelle: 2011
• Band/Heft Quelle: 13(2011), 12, Seite 670-679
• ISSN Quelle: 1521-2254
• DOI: doi:10.1002/jgm.1627
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: full-length codon-optimized merozoite surface protein-1 (MSP-1)
• Sach-SW: high capacity adenoviral vector
• Sach-SW: malaria
• Sach-SW: vaccine
• Sach-SW: ΔE1 adenoviral vector
• K10plus-PPN: 1831777266

Abstract

Background The merozoite surface protein (MSP)-1 of Plasmodium falciparum, the causative agent of malaria tropica, is considered to be a promising vaccine candidate. Although its stable cloning and expression has been difficult in the past, adenoviral vectors expressing the complex protein are described in the present study. Methods Codon-optimized msp-1 was used to construct a set of first generation (ΔE1Ad) and high-capacity adenovirus (HC-Ad) vectors, and cellular and humoral immune responses induced by the vectors were characterized in detail in mice. Results Generation of stable ΔE1Ad and HC-Ad vectors expressing full-length MSP-1 and their production to high vector titers was found to be feasible. Epitope identification and analysis of frequencies of specific CD8 T-cells revealed that MSP-1 expressing HC-Ad vectors induced higher frequencies of interferon-γ + CD8 T-cells than ΔE1 vectors. Irrespective of the vector format, higher titers of MSP-1 specific antibodies were generated by Ad vectors expressing MSP-1 from a chicken β-actin (CAG) promoter comprising the cytomegalovirus early enhancer element and the chicken β-actin promoter. Conclusions The findings of the present study suggest that Ad vectors expressing full-length codon-optimized MSP-1 are promising candidate vaccines against P. falciparum infections. Use of the HC-Ad vector type for delivery, as well as the CAG promoter to control MSP-1 expression, may further increase the efficacy of this vaccine candidate. Copyright © 2011 John Wiley & Sons, Ltd.