The pan HLA DR-binding epitope improves adjuvant-assisted immunization with a recombinant protein containing a malaria vaccine candidate.
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.
Rosa
Daniela Santoro
DS
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.
Tzelepis
Fanny
F
Cunha
Maristela G
MG
Soares
Irene S
IS
Rodrigues
Mauricio M
MM
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
D000939:Epitopes; D006684:HLA-DR Antigens; D017780:Malaria Vaccines; C401223:PADRE 45