Immunogenicity and efficacy in mice of two adjuvant formulations based on the C -and N-terminus of merozoite surface protein 1 of Plasmodium yoelii

The carboxyl-terminal fragment of MSP-1 is a potential malaria vaccine candidate, but its limited immunogenicity in humans has slowed clinical progress, needing the optimization of formulation of adjuvant and construct. In this study, the N- and C-terminal fragments of the PyMSP-1 (PyMSP-1 N and PyMSP-1C) were immunized to mice with either incomplete Freund's adjuvant (IFA) plus CpG ODN 1826 or Aluminum salts (Alum) plus CpG, followed by a challenge with Plasmodium yoelii 17XNL to investigate vaccine efficacy. Humoral response and antigen-specific T-cell-derived IFN-γ cytokines were analyzed to compare both fragments. After challenge infection, all mice immunized by PyMSP-1C in IFA plus CpG ODN survived with low-grade parasitemia, while 50 % of mice immunized with PyMSP-1 N in Alum plus CpG ODN died with high levels of parasitemia. Co-immunized with both fragments prevented parasitemia entirely, with IFA plus CpG adjuvants proving more suitable than Alum plus CpG. Both fragments elicited a comparable humoral response when they were formulated with IFA plus CpG ODN but PyMSP-1 N formulated with Alum plus CpG ODN significantly decreased the antigen-specific IgG level. While both IgG1 and IgG2c levels were comparable in two fragments formulated by IFA plus CpG ODN, it was efficient to induce the level of IgG2c of PyMSP-1 N fragment (P < 0.0001). Likewise, IFN-γ from both CD8⁺ and CD4⁺ T-cells was significantly lower by PyMSP-1 N than PyMSP-1C formulated in IFA plus CpG ODN (P < 0.0001). In conclusion, the N-terminal fragment of PyMSP-1 protected mice although it showed lower humoral and cellular immune response compared to C-terminal of MSP-1 in IFA plus CpG. The antibody level of PyMSP-1 N was comparable to that of PyMSP-1C when it was formulated with IFA plus CpG.