Prolonged expression of IFNgamma induced by protective blood-stage immunization against Plasmodium yoelii malaria

Mice vaccinated with whole blood-stage antigens of Plasmodium yoelii develop protective, antibody-mediated immune responses to homologous challenge infection. In this model the level of protection induced by whole parasite antigen vaccination is dependent on antibody isotype, which can be influenced by adjuvant formulations. In this study the ability adjuvant formulations to affect cytokine production and protection against P. yoelii blood-stage infection was investigated. Survival of mice in groups vaccinated with P. yoelii antigens in an aqueous mix of copolymer P1005 + RaLPS was 100%. Mice vaccinated with either P. yoelii antigens alone or combined with a water-in-oil emulsion of copolymer P1005 + RaLPS demonstrated 83 or 50% survival, respectively. The fully protective aqueous vaccine group produced higher levels of interferon gamma (IFNgamma) and interleukin 4 (IL-4) than the water-in-oil vaccine group following a live parasite challenge infection. Furthermore, mice vaccinated with the aqueous vaccine displayed prolonged IFNgamma and IL-4 response as compared to mice that received the same antigens without adjuvants. These data support the hypothesis that both the Th1 cytokine IFNgamma, and the Th2 cytokine IL-4 are modulated by the vaccine vehicle and adjuvant used for vaccination, thus possibly affecting expression of protective immune responses. However, it is the long-lasting IFNgamma response following blood-stage P. yoelii parasite challenge that is associated with enhanced survival.