A method of functionally screening protective antigenic polypeptides of a determined Plasmodium pathogen comprising the steps of: a. optionally pre-selecting candidate antigenic polypeptides for the screening by reference to a group of genes, transcripts or proteins identified for a determined Plasmodium pathogen wherein the antigenic polypeptides may constitute putative targets for a humoral and/or cellular immune response. b. providing a lentiviral vector, in particular a HIV-1 based vector, expressing one or more antigenic polypeptide(s) to be assayed for its (their) immunogenic properties, c. immunizing a non-human mammal in particular a non-human mammal model selected for its susceptibility to infection by the determined Plasmodium pathogen, with the lentiviral vector of step b. in immunization dose conditions enabling elicitation of a potent cellular and/or humoral memory response against the antigenic polypeptide(s), d. challenging the immunized non-human mammal of step c. with the Plasmodium pathogen administered to the immunized non-human mammal of step c. and quantifying the development of the Plasmodium pathogen wherein the quantification of the protective response against the antigenic polypeptide comprises a step of quantifying (i) the load of the sporozoites expressing a constitutive bioluminescent marker, in the liver of the non-human mammal by bioluminescence or (ii) the growth of the Plasmodium pathogen expressing a constitutive fluorescent marker, by determining fluorescence on red blood cells harvested from a blood sample of the non-human mammal, especially by flow cytometry, thereby enabling functional identification of the protective response capacity of the antigenic polypeptide(s). a. optionally pre-selecting candidate antigenic polypeptides for the screening by reference to a group of genes, transcripts or proteins identified for a determined Plasmodium pathogen wherein the antigenic polypeptides may constitute putative targets for a humoral and/or cellular immune response. b. providing a lentiviral vector, in particular a HIV-1 based vector, expressing one or more antigenic polypeptide(s) to be assayed for its (their) immunogenic properties, c. immunizing a non-human mammal in particular a non-human mammal model selected for its susceptibility to infection by the determined Plasmodium pathogen, with the lentiviral vector of step b. in immunization dose conditions enabling elicitation of a potent cellular and/or humoral memory response against the antigenic polypeptide(s), d. challenging the immunized non-human mammal of step c. with the Plasmodium pathogen administered to the immunized non-human mammal of step c. and quantifying the development of the Plasmodium pathogen wherein the quantification of the protective response against the antigenic polypeptide comprises a step of quantifying (i) the load of the sporozoites expressing a constitutive bioluminescent marker, in the liver of the non-human mammal by bioluminescence or (ii) the growth of the Plasmodium pathogen expressing a constitutive fluorescent marker, by determining fluorescence on red blood cells harvested from a blood sample of the non-human mammal, especially by flow cytometry, thereby enabling functional identification of the protective response capacity of the antigenic polypeptide(s).