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: Daniela Santoro Rosa, Fanny Tzelepis, Maristela G Cunha, Irene S Soares, Mauricio M Rodrigues
• Journal: Immunology letters (Immunol Lett) Vol. 92 Issue 3 Pg. 259-68 (Apr 15 2004) ISSN: 0165-2478 [Print] Netherlands
• PMID: 15081621 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes
• HLA-DR Antigens
• Malaria Vaccines
• PADRE 45

Topics

• Animals
• Cell Division (immunology)
• Epitopes (immunology)
• HLA-DR Antigens (immunology)
• Humans
• Immunity, Cellular (drug effects, immunology)
• Malaria Vaccines (immunology, pharmacology)
• Malaria, Falciparum (immunology, prevention & control)
• Mice
• Plasmodium falciparum (immunology)
• T-Cell Antigen Receptor Specificity (immunology)
• T-Lymphocytes (cytology, immunology)