Immunomodulatory effects of Plasmodium berghei expressed mouse interferon gamma culture supernatants in mice challenged with homologous wild-type parasites

Abstract

Malaria causes up to 755,000 deaths per year, worldwide. Availability of an affordable, long lasting, safe and effective malaria vaccine would be very appropriate in reducing the disease burden by bridging the gap left by other malaria interventions. Most malaria vaccine development approaches have faced challenges such as the choice of appropriate adjuvant and inconsistent efficacy results during trials. Search for a feasible malaria vaccine continues. Use of whole-organism vaccines such as live attenuated or immunopotentiated parasites could resolve this challenge. Cytokine immunopotentiation of Plasmodium parasites may provide an important approach towards development of a potent malaria vaccine. This study aimed at exploring immunomodulatory potential of parasite expressed mouse interferon gamma (mIFN-γ) in a malaria model with a view of contributing to malaria vaccine development strategies. Transfection was used to generate interferon gamma (IFN-γ) producing Plasmodium berghei parasites. A randomized controlled study design was adopted. The design constituted four treatment groups; one test group and three control groups. There were three sampling points. Each treatment group constituted five mice at each sapling point. In total, sixty mice were used. The parasites were cultured and IFN-γ culture supernatants collected. Mice were immunized with the parasite expressed mIFN-γ culture supernatants. Fourteen days later, they were later intraperitoneally challenged with wild-type parasites. Sampling for cytokine and antibody assays was done and ELISA performed on the collected samples. Parasitaemia was monitored daily and survival time (days) recorded. Analysis of variance (ANOVA) was used to analyze the results using graphpad instat software. The group pre-treated with IFN-γ P. berghei culture supernatants exhibited significantly higher levels of IFN-γ (p < 0.001). The level of IL-4 in this group was significantly low (p < 0.05). There was no significant difference in the levels of IgG (p = 0.0682) amongst all the treatment groups. Mean parasitaemia was significantly reduced (p = 0.023) in the group pre-exposed to IFN-γ expressing P. berghei culture supernatants compared with the controls. There was a 4 day delay in onset of patent parasitaemia accompanied by higher parasitaemia suppression (94.15% on day 11 post-infection). The survival time of the mice was 5 days longer than that of the controls. The findings of this study have demonstrated the potential for culture supernatants of IFN-γ expressing P. berghei in protecting mice against virulent infection. The study has set a pace for adoption of interferon gamma immunopotentiation of Plasmodium as an approach to attenuated malaria vaccine development. However, further studies need to done to shed more light on host protection against active infection. Such studies include purifying the P. berghei expressed mouse IFN-γ and determining its effect on murine malaria at different concentrations and time points during infection, in synergy with whole parasite antigen.