Understanding the Liver-Stage Biology of Malaria Parasites: Insights to Enable and Accelerate the Development of a Highly Efficacious Vaccine

Abstract

Abstract.In August 2017, the National Institute of Allergy and Infectious Diseases convened a meeting, entitled “Understanding the Liver-Stage Biology of Malaria Parasites to Enable and Accelerate the Development of a Highly Efficacious Vaccine,” to discuss the needs and strategies to develop a highly efficacious, whole organism–based vaccine targeting the liver stage of malaria parasites. It was concluded that attenuated sporozoite platforms have proven to be promising approaches, and that late-arresting sporozoites could potentially offer greater vaccine performance than early-arresting sporozoites against malaria. New knowledge and emerging technologies have made the development of late-arresting sporozoites feasible. Highly integrated approaches involving liver-stage research, “omics” studies, and cutting-edge genetic editing technologies, combined with in vitro culture systems or unique animal models, are needed to accelerate the discovery of candidates for a late-arresting, genetically attenuated parasite vaccine.

Type I Interferons and Malaria: A Double-Edge Sword Against a Complex Parasitic Disease

“…Sterile protection against Plasmodium infection can be achieved through exposure to radiation-or genetically-attenuated sporozoites that are able to infect but cannot replicate within the hepatocyte, or through exposure to sporozoites under chloroquine chemoprophylaxis (Mo and McGugan, 2018). It appears that IFN-Is are part of protective immunity during normal or attenuated sporozoite infection; however, the roles of IFN-Is in infections by sporozoites attenuated by various methods has not been well A B FIGURE 3 | Timing and levels of interferon production may determine the outcomes of malaria parasite infections.…”

Zonal human hepatocytes are differentially permissive to Plasmodium falciparum malaria parasites

“…Subsequently, low numbers of deposited sporozoites invade, differentiate, and massively multiply (as schizont forms) inside hepatocytes followed by release of blood-infective merozoites via merosomes into the circulation in rodent malaria models (Sturm et al, 2006). Cycles of asexual parasite multiplication in circulating red blood cells are responsible for malaria morbidity and mortality (Mo & McGugan, 2018).…”

The role of the liver in the migration of parasites of global significance

“…However, before a vaccine can be developed, an in-depth understanding of this stage is necessary. The National Institute of Allergy and Infectious Diseases recently identified ‘greater understanding of parasite liver-stage biology and development’ as a key challenge in malaria vaccine development [80].…”