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 19 kDa 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 6MSP1 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 6MSP1 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 6MSP1 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.