Delta E1 and high-capacity adenoviral vectors expressing full-length codon-optimized merozoite surface protein 1 for vaccination against Plasmodium falciparum

作者：Zong Shan; Kron Matthias W; Epp Christian; Engler Tatjana; Bujard Hermann; Kochanek Stefan; Kreppel Florian^*

来源：Journal of Gene Medicine, 2011, 13(12): 670-679.

DOI：10.1002/jgm.1627

• Delta E1 adenoviral vector
• full-length codon-optimized merozoite surface protein-1 (MSP-1)
• high capacity adenoviral vector
• malaria
• vaccine

Background Themerozoite 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 (Delta E1Ad) 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 Delta E1Ad 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-gamma+ CD8 T-cells than Delta E1 vectors. Irrespective of the vector format, higher titers of MSP-1 specific antibodies were generated by Ad vectors expressing MSP-1 from a chicken beta-actin (CAG) promoter comprising the cytomegalovirus early enhancer element and the chicken beta-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.

• 出版日期2011-12