The Development of Whole Sporozoite Vaccines for Plasmodium falciparum Malaria

Abstract

Each year malaria kills hundreds of thousands of people and infects hundreds of millions of people despite current control measures. An effective malaria vaccine will likely be necessary to aid in malaria eradication. Vaccination using whole sporozoites provides an increased repertoire of immunogens compared to subunit vaccines across at least two life cycle stages of the parasite, the extracellular sporozoite, and intracellular liver stage. Three potential whole sporozoite vaccine approaches are under development and include genetically attenuated parasites, radiation attenuated sporozoites, and wild-type sporozoites administered in combination with chemoprophylaxis. Pre-clinical and clinical studies have demonstrated whole sporozoite vaccine immunogenicity, including humoral and cellular immunity and a range of vaccine efficacy that depends on the pre-exposure of vaccinated individuals. While whole sporozoite vaccines can provide protection against malaria in some cases, more recent studies in malaria-endemic regions demonstrate the need for improvements. Moreover, challenges remain in manufacturing large quantities of sporozoites for vaccine commercialization. A promising solution to the whole sporozoite manufacturing challenge is in vitro culturing methodology, which has been described for several Plasmodium species, including the major disease-causing human malaria parasite, Plasmodium falciparum. Here, we review whole sporozoite vaccine immunogenicity and in vitro culturing platforms for sporozoite production.

Identification and characterization of protective CD8+ T‐epitopes in a malaria vaccine candidate SLTRiP

“…[7][8][9][10][11] Immunization using chemically and or genetically attenuated malaria parasites have been shown to provide immunity against multiple strains of Plasmodium parasite. [12][13][14] However, the approach faces the challenges of manufacture cost, storage, and distribution of parasite, thus limiting the use of this approach in endemic areas. Conversely, a subunit vaccine includes one or multiple protein antigen that may or may not be coupled to immunogenic and protective epitopes.…”

Extensive Transcriptional and Translational Regulation Occur During the Maturation of Malaria Parasite Sporozoites

“…Accomplishing this will require greater knowledge of the basic biology of the pre-erythrocytic sporozoite and liver stage parasites. Promising new whole-parasite vaccine candidates, based upon the sporozoite form of the parasite, are on the horizon and hopefully will meet these needs 2 .…”

“…Following this, sporozoites exit the bite site in the skin, locate and enter the vasculature, and passively travel to the liver, where sporozoites can productively infect hepatocytes, which initiates the life cycle progression in the mammalian host 7 . Moreover, because relatively few sporozoites are injected during a mosquito bite 8 , this transmission event bottleneck has been the focus of intervention efforts using drugs, subunit vaccines, and attenuated whole parasite vaccines 2 .…”

CRISPR/Cas9-engineered inducible gametocyte producer lines as a novel tool for basic and applied research onPlasmodium falciparummalaria transmission stages

“…Moreover, NF54/iGP gametocytes will support studies investigating sexual reproduction and subsequent parasite development in mosquitoes as well as parasite-vector interactions and vector competence. Potentially, NF54/iGP gametocytes may also be applicable for the development and validation of transmission-blocking vaccines and may provide a reliable resource for the production of sporozoites for hepatocyte infection models and for the optimization of protocols aiming to produce zygotes, ookinetes, oocysts and sporozoites in vitro 87-89 (Fig. 6).…”