Protective immune mechanisms against pre-erythrocytic forms of Plasmodium berghei depend on the target antigen

• Non invasive imaging of immune responses is achieved using the IVIS® system.
• The study revealed the anatomical site of anti-parasite immune responses using IVIS®.
• The study investigates the immune effector mechanism targeting two malarial antigens.
• CSP-specific immune responses induced by gene gun immunization target the skin.
• CelTOS-specific responses target parasites in both, the skin and the liver.

Pre-erythrocytic malaria vaccines are believed to either stop the injected sporozoites from reaching the liver or to direct cellular immune responses towards eliminating infected hepatocytes. The present study reveals for the first time the anatomical sites at which these immune mechanisms act against the malaria parasites. To determine the mechanisms leading to protection mediated by two previously characterized vaccines against either the circumsporozoite protein (CSP) or the cell traversal protein for ookinetes and sporozoites (CelTOS), mice were immunized and subsequently challenged by subcutaneous injection of salivary gland sporozoites of luciferase-transgenic Plasmodium berghei parasites. The In Vivo Imaging System (IVIS) was used to identify the anatomical site where the vaccine-induced immune response eliminates sporozoites after injection. The data demonstrate that CSP-based immunity acts at the site of infection (skin) whereas CelTOS-based immunity is only partially efficient in the skin and allows reduced levels of liver infection that can be subsequently cleared. The results of this study challenge assumptions regarding CSP-mediated immune mechanisms and call into question the validity of some commonly used assays to evaluate anti-CSP immune responses. The knowledge of the mechanism and events leading to infection or immune defense will guide supportive treatment with drugs or combination therapies and thus accelerate the development of effective antimalarial strategies.