Vaccination against malaria with live parasites

Abstract

Despite nearly 80 years of vaccine research and control efforts, malaria remains one of the most prevalent of all infectious diseases. The fact that people living in regions in which malaria is endemic eventually develop immunity to the parasite and the disease suggest that it might be possible to develop vaccines against malaria. Although few vaccination trials were conducted with whole parasites, the only protocol that leads to the induction of sterile immunity in humans relies on immunization with attenuated parasites. This observation has spurred the search for subunit vaccines that aim to reproduce this protection. As yet, none of the current candidate subunit vaccines have achieved complete protection reproducibly. This failure, coupled with the recent advent of the genetically modified Plasmodium parasites, has led to a renewed interest in the use of live parasites for vaccination. This article reviews past studies, summarizes recent developments in this field and discusses the challenges to be overcome before mass immunization with live parasites could be envisaged.

Protracted Sterile Protection withPlasmodium yoeliiPre‐erythrocytic Genetically Attenuated Parasite Malaria Vaccines Is Independent of Significant Liver‐Stage Persistence and Is Mediated by CD8+T Cells

“…Therefore, the search for an optimally attenuated P. falciparum GAP should be initiated and may yield a single-dose malaria vaccine that confers complete, long-lasting protection against initial infection. Although, selection, production, and deployment of a live attenuated malaria vaccine faces many formidable obstacles [32], it may ultimately provide the only opportunity to completely protect humans against malaria infection by vaccination.…”

Live and let die: manipulation of host hepatocytes by exoerythrocytic Plasmodium parasites

“…In addition, Plasmodium parasites remain for several days in hepatocytes that should allow enough time for the immune system of a vaccinated individual to eliminate the infection at this early stage. Research performed in humans and mice has shown that irradiated or genetically attenuated sporozoites are able to confer protection against challenge with wild type parasites [5][6][7][8]. In spite of this knowledge and the recent eVort to mass-produce irradiated sporozoites for vaccination trials [9,10], a commercial vaccine against malaria is still not available.…”

Plasmodium yoelii Sporozoites with Simultaneous Deletion of P52 and P36 Are Completely Attenuated and Confer Sterile Immunity against Infection

“…Immunizations with uis3-or uis4-deficient sporozoites completely protected mice against subsequent infectious sporozoite challenge (21,22). The use of genetically attenuated parasites (GAPs) as a live attenuated malaria vaccine for humans may thus hold great promise, but a critical issue to be addressed is the proper complete attenuation of the vaccine (8,26). Single-gene deletions may not be sufficient to completely attenuate the parasite, and therefore, vaccination could lead to breakthrough infections.…”