title: ΔE1 and high-capacity adenoviral vectors expressing full-length codon-optimized merozoite surface protein 1 for vaccination against Plasmodium falciparum.
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.
authors.affiliation: Department of Gene Therapy, University of Ulm, Ulm, Germany.
authors.forename: Shan
authors.initials: S
authors.lastname: Zong
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Kron
authors.forename: Christian
authors.initials: C
authors.lastname: Epp
authors.forename: Tatjana
authors.initials: T
authors.lastname: Engler
authors.forename: Hermann
authors.initials: H
authors.lastname: Bujard
authors.forename: Stefan
authors.initials: S
authors.lastname: Kochanek
authors.forename: Florian
authors.initials: F
authors.lastname: Kreppel
mesh_terms: D062705:Adenovirus Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000818:Animals; D000918:Antibody Specificity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003062:Codon / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016778:Malaria, Falciparum / Q000235:genetics / Q000628:therapy*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity; D011401:Promoter Regions, Genetic
chemical_list: D062705:Adenovirus Vaccines; D003062:Codon; D020066:Merozoite Surface Protein 1; D007371:Interferon-gamma