title: An expanding toolkit for preclinical pre-erythrocytic malaria vaccine development: bridging traditional mouse malaria models and human trials.
abstract: Malaria remains a significant public health burden with 214 million new infections and over 400,000 deaths in 2015. Elucidating relevant Plasmodium parasite biology can lead to the identification of novel ways to control and ultimately eliminate the parasite within geographic areas. Particularly, the development of an effective vaccine that targets the clinically silent pre-erythrocytic stages of infection would significantly augment existing malaria elimination tools by preventing both the onset of blood-stage infection/disease as well as spread of the parasite through mosquito transmission. In this Perspective, we discuss the role of small animal models in pre-erythrocytic stage vaccine development, highlighting how human liver-chimeric and human immune system mice are emerging as valuable components of these efforts.
authors.affiliation: Center for Infectious Disease Research, Formerly Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors.forename: Ryan Wj
authors.initials: RW
authors.lastname: Steel
authors.affiliation: Center for Infectious Disease Research, Formerly Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors.forename: Stefan Hi
authors.initials: SH
authors.lastname: Kappe
authors.affiliation: Center for Infectious Disease Research, Formerly Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Sack
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology; D006801:Humans; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control* / Q000635:transmission; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D010961:Plasmodium / Q000235:genetics / Q000276:immunology; D057170:Translational Research, Biomedical
chemical_list: D017780:Malaria Vaccines
keywords: Plasmodium; antigen identification; cellular and humoral immunity; human immune system mice; human liver-chimeric mice; in vitro assays; malaria; pre-erythrocytic vaccine; whole-sporozoite immunization