Evaluation Of Cytokine Responses To Plasmodium Falciparum Transmission Blocking Vaccine Candidates In A Rodent Model

Abstract

Over the past decades, much progress has been made towards the control and elimination of malaria in endemic regions and great successes have been achieved so far but the insecticide-resistant mosquitoes and drug-resistant parasites pose a major threat to successes achieved so far through these intervention measures. Vaccines that could interrupt the transmission of malaria parasites are being sought as more lasting and effective control measures. Two of the most promising malaria transmission blocking vaccine candidates, Pfs230 and Pfs48/45 have been produced in recombinant forms and tested independently in rodent models sometimes with contrasting findings. This study hypothesized that a combined immunization with equivalent doses of Pfs230 and Pfs48/45-6C would elicit a stronger cytokine response that may favor antibody production than their individual antigens. Levels of interleukins IL-1 beta, IL-1alpha, IL-2, IL-6, IL-10, IL-12, TNF-alpha, IFN-gamma levels with different dosses antigens were assessed. Of the two antigens, Pfs230 induced the stronger cytokine responses while levels measured in rats vaccinated with Pfs48/45-6C were lower than Pfs230/Pfs48/45-6C (p=0.001). For both antigens, it appeared the lower dose (1.5 µg) induced much stronger cytokine responses compared to the higher (6.0 µg) dose (p=0.001). This has led to the formulation of the hypothesis that; the higher dose might have induced a state of immune tolerance in this group of rats thus resulting in a lowered cytokine response. This needs to be tested in future studies. Interestingly, when the single formulations were compared to the combined formulations involving both antigens, the single antigens elicited higher cytokine responses than the combined formulations (p=0.001). Further studies should be carried out to investigate antibody and cytokine responses concurrently in rats vaccinated with different doses of the antigens.