title: A bicomponent Plasmodium falciparum investigational vaccine composed of protein-peptide conjugates.
abstract: There is yet no licensed vaccine against malaria, a serious human disease affecting mostly children, with an annual death rate of about one million. Plasmodia, the malaria-causing parasites, have two obligatory hosts: mammals or birds, in which they multiply asexually, and mosquitoes with sexual multiplication. The most common and serious type of malaria is caused by Plasmodium falciparum. The circumsporozoite protein (CSP), a major surface antigen of sporozoites, is a protective antigen. A unique feature of P. falciparum CSP is its large central domain composed of over 30 tetrapeptide repeats of Asn-Ala-Asn-Pro (NANP). Several NANP peptide-protein conjugates were tested clinically but elicited a low level of CSP antibodies for a short duration. To provide a CSP-based candidate vaccine, we investigated recombinant CSP and NANP conjugates of various peptide lengths, with different N-terminal amino acids, bound at different ratios to various carrier proteins. Injected into mice, CSP alone and CSP or NANP conjugates induced antibodies with booster responses and were positive by the sporozoite immunofluorescent assay. The use of the mosquito stage P. falciparum ookinete surface protein, Pfs25, cross-linked onto itself as a carrier for NANP, induced in mice high levels of uniquely long-lasting antibodies to both vaccine components with secondary biological activities, that will provide immunity to liver infection by sporozoites and block transmission by mosquitoes.
authors.affiliation: Program on Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kubler-Kielb
authors.forename: Fathy
authors.initials: F
authors.lastname: Majadly
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Biesova
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Mocca
authors.forename: Chunyan
authors.initials: C
authors.lastname: Guo
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussenzweig
authors.forename: Victor
authors.initials: V
authors.lastname: Nussenzweig
authors.forename: Satish
authors.initials: S
authors.lastname: Mishra
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wu
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Keith
authors.forename: Teh-Yung
authors.initials: TY
authors.lastname: Liu
authors.forename: John B
authors.initials: JB
authors.lastname: Robbins
authors.forename: Rachel
authors.initials: R
authors.lastname: Schneerson
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D008401:Gas Chromatography-Mass Spectrometry; D017780:Malaria Vaccines / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; D010455:Peptides; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C041595:circumsporozoite protein, Protozoan