Using a variety of anti-malaria tools has resulted in a steady decline of malaria in several endemic countries worldwide. An effective vaccine will be critical to halt malaria or even succeed to... Show moreUsing a variety of anti-malaria tools has resulted in a steady decline of malaria in several endemic countries worldwide. An effective vaccine will be critical to halt malaria or even succeed to final eradication. In that perspective, we studied the potential of whole sporozoite immunization by bites of P. falciparum infected mosquitoes under chemoprophylaxis (CPS). In this thesis we further explored this CPS model and assessed different immunizing doses, type of chemoprophylaxis and immunological determinants of disease and protection. We found a clear dose dependent efficacy, independent of type of chemoprophylaxis, found CD107a and CD8 T cells producing granzyme B related to protective immunity. In the field many genetically different strains circulate and a future vaccine should be able to cover multiple strains. We re-challenged volunteers with a different strain and found modest heterologously protection.We retrospectively assessed the parasitological dynamics and adverse events using a positive qPCR rather than thick smear and found reduced the clinical symptoms of malaria for volunteers after challenge.Successful malaria eradication will be more likely to be achieved with a multi-disciplinary approach. Additionally, sufficient and continuous funds will proof to be of tremendous necessity. Show less