Reduced antibody response to the repetitive sequence of the Plasmodium falciparum circumsporozoite protein in mice infected with Plasmodium yoelii blood forms

Abstract

The immunogenicity of the carrier-free synthetic peptide, (NANP)40, from the repetitive region of the Plasmodium falciparum circumsporozoite (CS) protein was investigated in genetically responder mice (C57BL/6, H-2b) acutely infected with blood forms of the non-lethal murine malaria parasite, P. yoelii. As compared to non-infected mice, P. yoelii-infected C57BL/6 mice produced significantly lower titers of anti-(NANP)40 IgG antibodies. This decrease in the anti-(NANP)40 antibody response peaked with the peak of parasitemia, and involved all the IgG subclasses. Interestingly, this P. yoelii-mediated effect was evident both on the development of the antibody response to the (NANP)40 peptide, and on an already established anti-(NANP)40 antibody titer, as seen in mice immunized with the peptide 1 month before the infection. Since (NANP)n-based constructs are strongly envisaged as potential vaccines against falciparum malaria, these results might be important in the evaluation of the efficacy of these vaccine candidates, when they will be used in individuals living in endemic areas.

In vitro Antibody Response to the Tetrapeptide Repeats of Plasmodium falciparum Circumsporozoite Protein by Splenocytes from Mice Infected with P. yoelii yoelii.

“…Grillot et al [4] reported that mice immunized with synthetic peptide, (NANP) 40 , emulsified with complete Freund's adjuvant also showed suppressed antibody responses to the peptide during P. yoelii malaria infection. In their experiment, however, immunization of the synthetic peptide was carried out only once during infection and the mice were periodically examined for antibody response after that.…”

“…We and others have demonstrated that the splenic macrophages of the malarious mice were functionally defective as accessory cells in antibody response to horse and sheep erythrocytes [1,11,17,18]. On the other hand, Grillot et al [4] reported that mice immunized with repetitive region of P. falciparum circumsporozoite (CS) protein, (NANP) 40 , also showed suppressed antibody responses to the synthetic peptide during P. yoelii malaria infection. However, the mechanisms responsible for the suppression induced by P. yoelii malaria remain to be determined.…”