title: Potent immunogenic short linear peptide constructs composed of B cell epitopes and Pan DR T helper epitopes (PADRE) for antibody responses in vivo.
abstract: Induction of humoral immune responses against protein antigen requires that two independent signals be delivered to B cells. It is currently assumed that simple monovalent synthetic peptides would not be effective immunogens for antibody responses because they would not be anticipated to effectively generate the necessary signals unless conjugated to a complex carrier system. In this study, the immunogenicity of short linear peptide constructs comprising Plasmodium vivax B cell epitopes (PVB) and non-natural Pan-DR T helper cell epitopes (PADRE) was assessed in mice and compared to other types of antigen constructs. The 33-residue PADRE-PVB linear constructs were highly immunogenic and induced responses comparable to those obtained with the multiple antigen peptides (MAP) constructs, both in terms of absolute titers and quality of antibody responses. The anti-PVB antibody responses were of long duration, composed mostly of IgG and reactive with intact sporozoites. The PADRE-PVB constructs were immunogenic when formulated in adjuvants such as Alum and Montanide ISA 51 underlining the relevance of these findings for vaccine development.
authors.affiliation: Cytel Corporation, San Diego, CA 92121, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: del Guercio
authors.forename: J
authors.initials: J
authors.lastname: Alexander
authors.forename: R T
authors.initials: RT
authors.lastname: Kubo
authors.forename: T
authors.initials: T
authors.lastname: Arrhenius
authors.forename: A
authors.initials: A
authors.lastname: Maewal
authors.forename: E
authors.initials: E
authors.lastname: Appella
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffman
authors.forename: T
authors.initials: T
authors.lastname: Jones
authors.forename: D
authors.initials: D
authors.lastname: Valmori
authors.forename: K
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: H M
authors.initials: HM
authors.lastname: Grey
authors.forename: A
authors.initials: A
authors.lastname: Sette
mesh_terms: D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000953:Antigens, Protozoan / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry* / Q000276:immunology; D006684:HLA-DR Antigens / Q000737:chemistry / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D010966:Plasmodium vivax / Q000254:growth & development / Q000276:immunology; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D017780:Malaria Vaccines; D010455:Peptides; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; D000536:Aluminum Hydroxide