title: Long-lasting humoral and cellular immune responses elicited by immunization with recombinant chimeras of the Plasmodium vivax circumsporozoite protein.
abstract: The circumsporozoite protein (CSP), the most abundant surface antigen of sporozoites, has been extensively studied in different expression platforms as a vaccine candidate. Clinical trials have shown the necessity of broad and highly avid humoral immune responses together with high numbers of CSP-specific TCD4+ and TCD8+ cells, especially those producing IFN-γ, to induce protection. To this aim, we designed two distinct recombinant immunogens based on previously-described antigenic fragments of Plasmodium vivax CSP (PvCSP) to be used as vaccine candidates. The first one is a virus-like particle (VLP) comprising the repeat region of PvCSP (B and TCD4+ epitopes) within the loop of the hepatitis B virus core antigen (HBcAgPvCSP). The second one is a PvCSP multi-epitope polypeptide, rPvCSP-ME, designed based on antigenic regions of PvCSP recognized by lymphocytes of individuals from endemic areas. Mice immunized with 2 doses of these proteins, administered individually or combined and formulated in Montanide ISA 720 adjuvant, were able to induce strong effector and memory humoral responses with IgG titers ranging from 10(4) to 10(5) and avidity indexes toward full-length PvCSP reaching up to 66%, even 3 months after the last immunization. Furthermore, balanced Th1/Th2 responses were generated, as determined by titers of IgG subclasses and further confirmed by ELISPOT analyses, which detected that these vaccination protocols were able to elicit long-term IFN-γ and IL-2-secreting memory T-cells. Overall, these results show that our vaccine candidates generate, in mice, immune responses against regions within PvCSP that have been associated with protection against malaria in humans.
authors.affiliation: Departamento de Microbiologia, ICB, UFMG, Brazil.
authors.forename: Ana Paula Morais Martins
authors.initials: AP
authors.lastname: Almeida
authors.affiliation: Departamento de Microbiologia, ICB, UFMG, Brazil.
authors.forename: Mariana Oliveira
authors.initials: MO
authors.lastname: Dias
authors.affiliation: Departamento de Microbiologia, ICB, UFMG, Brazil.
authors.forename: Carolina de Almeida Fagundes
authors.initials: Cde A
authors.lastname: Vieira
authors.affiliation: Departamento de Bioquímica e Imunologia, ICB, UFMG, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Chávez-Olórtegui
authors.affiliation: Departamento de Bioquímica e Imunologia, ICB, UFMG, Brazil.
authors.forename: Ricardo Tostes
authors.initials: RT
authors.lastname: Gazzineli
authors.affiliation: Escola Paulista de Medicina, UNIFESP, Brazil.
authors.forename: Maurício Martins
authors.initials: MM
authors.lastname: Rodrigues
authors.affiliation: Departamento de Parasitologia, ICB, UFMG, Brazil.
authors.forename: Ricardo Toshio
authors.initials: RT
authors.lastname: Fujiwara
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, CCB, UFSC, Brazil. Electronic address: oscar.bruna.romero@ufsc.br.
authors.forename: Oscar
authors.initials: O
authors.lastname: Bruna-Romero
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000915:Antibody Affinity; D000939:Epitopes / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008288:Malaria / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010966:Plasmodium vivax; D015800:Protozoan Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000939:Epitopes; D007074:Immunoglobulin G; D007376:Interleukin-2; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma
keywords: Circumsporozoite protein; Malaria; Plasmodium vivax; Vaccine; Virus-like particle