Antibody-dependent immune responses elicited by blood stage-malaria infection contribute to protective immunity to the pre-erythrocytic stages

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Abstract

Advances in transcriptomics and proteomics have revealed that different life-cycle stages of the malaria parasite, share antigens, thus allowing for the possibility of eliciting immunity to a parasite life-cycle stage that has not been experienced before. Using the (AS strain) model of malaria in mice, we investigated how isolated exposure to blood-stage infection, bypassing a liver-stage infection, yields significant protection to sporozoite challenge resulting in lower liver parasite burdens. Antibodies are the main immune driver of this protection. Antibodies induced by blood-stage infection recognise proteins on the surface of sporozoites and can impair sporozoite gliding motility suggesting a possible function Furthermore, mice lacking B cells and/or secreted antibodies are not protected against a sporozoite challenge in mice that had a previous blood-stage infection. Conversely, effector CD4 and CD8 T cells do not seem to play a role in protection from sporozoite challenge of mice previously exposed only to the blood stages of . The protective response against pre-erythrocytic stages can be induced by infections initiated by serially passaged blood-stage parasites as well as recently mosquito transmitted parasites and is effective against a different strain of (CB strain), but not against another rodent malaria species, . The possibility to induce protective cross-stage antibodies advocates the need to consider both stage-specific and cross-stage immune responses to malaria, as natural infection elicits exposure to all life-cycle stages. Future investigation into these cross-stage antibodies allows the opportunity for candidate antigens to contribute to malaria vaccine development.