Murine infection models for vaccine development: the malaria example.

Abstract

Vaccines are developed and eventually licensed following consecutive human clinical trials. Malaria is a potential fatal vector-borne infectious disease caused by blood infection of the single-cell eukaryote Plasmodium. Pathogen stage conversion is a hallmark of parasites in general and permits unprecedented vaccine strategies. In the case of malaria, experimental human challenge infections with Plasmodium falciparum sporozoites can be performed under rigorous clinical supervision. This rare opportunity in vaccinology has permitted many small-scale phase II anti-malaria vaccine studies using experimental homologous challenge infections. Demonstration of safety and lasting sterile protection are central endpoints to advance a candidate malaria vaccine approach to phase II field trials. A growing list of antigens as targets for subunit development makes pre-selection and prioritization of vaccine candidates in murine infection models increasingly important. Preclinical assessment in challenge studies with murine Plasmodium species also led to the development of whole organism vaccine approaches. They include live attenuated, metabolically active parasites that educate effector memory T cells to recognize and inactivate developing parasites inside host cells. Here, opportunities from integrating challenge experiments with murine Plasmodium parasites into malaria vaccine development will be discussed.