Gene Gun Immunization to Combat Malaria

DNA immunization by gene gun against a variety of infectious diseases has yielded promising results in animal models. Skin-based DNA vaccination against these diseases is not only an attractive option for the clinic but can aid in the discovery and optimization of vaccine candidates. Vaccination against the protozoan parasite Plasmodium presents unique challenges: (a) most parasite-associated antigens are stage-specific; (b) antibodies capable of neutralizing the parasite during the probing of the mosquitoes have to be available at high titers in order to prevent infection of the liver; (c) immunity to liver-stage infection needs to be absolute in order to prevent subsequent blood-stage parasitemia. Gene gun vaccination has successfully been used to prevent the infection of mice with the rodent malaria strain P. berghei and has been employed in a macaque model of human P. falciparum . DNA plasmid delivery by gene gun offers the opportunity to economically and efficiently test novel malaria vaccine candidates and vaccination strategies, which include the evaluation of novel molecular adjuvant strategies. Here we describe the procedures involved in making and delivering a pre-clinical malaria DNA vaccine by gene gun as well as the correct approach for the in vivo evaluation of the vaccine. Furthermore, we discuss various approaches that either have already been tested or could be employed to improve DNA vaccines against malaria.