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ΔE1 and high‐capacity adenoviral vectors expressing full‐length codon‐optimized merozoite surface protein 1 for vaccination against Plasmodium falciparum
Author(s) -
Zong Shan,
Kron Matthias W.,
Epp Christian,
Engler Tatjana,
Bujard Hermann,
Kochanek Stefan,
Kreppel Florian
Publication year - 2011
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1627
Subject(s) - virology , plasmodium falciparum , biology , vector (molecular biology) , viral vector , epitope , cd8 , merozoite surface protein , titer , enhancer , immune system , antibody , gene , microbiology and biotechnology , malaria vaccine , malaria , virus , genetics , recombinant dna , gene expression , immunology
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.