title: The pan HLA DR-binding epitope improves adjuvant-assisted immunization with a recombinant protein containing a malaria vaccine candidate.
abstract: The pan HLA DR-binding epitope (PADRE) has been proposed as a simple carrier epitope suitable for use in the development of synthetic and recombinant vaccines. Using the mouse model, we evaluated whether PADRE could improve adjuvant-assisted immunizations with a recombinant malarial protein containing the 19kDa C-terminal region of merozoite surface protein 1 (MSP1(19)) that is a Plasmodium vivax vaccine candidate. Initially, the antibody immune response was evaluated in C57BL/6 mice, a mouse strain which develops a strong T cell immune response to PADRE. When administered in distinct adjuvant formulations, antibody titers induced by the recombinant protein His(6)MSP1(19)-PADRE were not significantly different to those generated by complete/incomplete Freund's adjuvant (CFA/IFA) in terms of magnitude, affinity, IgG subclasses and longevity. However, in C57BL/6 mice immunized with the recombinant protein His(6)MSP1(19), strong antibody responses could be generated in the presence of CFA/IFA but not other classes of adjuvants such as CpG ODN 1826 or MPL/TDM. Similarly, in BALB/c mice that do not develop T cells specific for PADRE, the recombinant protein His(6)MSP1(19)-PADRE failed to induce high antibody titers in the presence of adjuvants other than CFA/IFA. Our results indicated that when adjuvants that are not as strong as CFA/IFA are employed, the presence of PADRE greatly improved adjuvant-assisted antibody immune responses induced by a malarial recombinant antigen. Considering the great limitations of adjuvants for human use, our observation may improve the rational design of new vaccine formulations.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Botucatu 862, 6th Floor, São Paulo 04023-062, SP, Brazil.
authors.forename: Daniela Santoro
authors.initials: DS
authors.lastname: Rosa
authors.forename: Fanny
authors.initials: F
authors.lastname: Tzelepis
authors.forename: Maristela G
authors.initials: MG
authors.lastname: Cunha
authors.forename: Irene S
authors.initials: IS
authors.lastname: Soares
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D002455:Cell Division / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology* / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D017780:Malaria Vaccines; C401223:PADRE 45