title: A nonadjuvanted polypeptide nanoparticle vaccine confers long-lasting protection against rodent malaria.
abstract: We have designed and produced a prototypic malaria vaccine based on a highly versatile self-assembling polypeptide nanoparticle (SAPN) platform that can repetitively display antigenic epitopes. We used this platform to display a tandem repeat of the B cell immunodominant repeat epitope (DPPPPNPN)(2)D of the malaria parasite Plasmodium berghei circumsporozoite protein. Administered in saline, without the need for a heterologous adjuvant, the SAPN construct P4c-Mal conferred a long-lived, protective immune response to mice with a broad range of genetically distinct immune backgrounds including the H-2(b), H-2(d), and H-2(k) alleles. Immunized mice produced a CD4(+) T cell-dependent, high-titer, long-lasting, high-avidity Ab response against the B cell epitope. Mice were protected against an initial challenge of parasites up to 6 mo after the last immunization or for up to 15 mo against a second challenge after an initial challenge of parasites had successfully been cleared. Furthermore, we demonstrate that the SAPN platform not only functions to deliver an ordered repetitive array of B cell peptide epitopes but operates as a classical immunological carrier to provide cognate help to the P4c-Mal-specific B cells.
authors.affiliation: Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Kaba
authors.forename: Clara
authors.initials: C
authors.lastname: Brando
authors.forename: Qin
authors.initials: Q
authors.lastname: Guo
authors.forename: Christian
authors.initials: C
authors.lastname: Mittelholzer
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Raman
authors.forename: David
authors.initials: D
authors.lastname: Tropel
authors.forename: Ueli
authors.initials: U
authors.lastname: Aebi
authors.forename: Peter
authors.initials: P
authors.lastname: Burkhard
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000915:Antibody Affinity; D000953:Antigens, Protozoan / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use*; D010962:Plasmodium berghei / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D010455:Peptides