Pre-erythrocytic Immunity in Malaria

Krzych, Urszula; Zarling, Stasya; Pichugin, Alexander

doi:10.1007/978-1-4614-8757-9_137-1

Cited by 2 publications

(1 citation statement)

References 56 publications

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“…To this end, we examined the generation of CD4 and CD8 effector memory (Tem) and central memory (Tcm), defined on the basis of the surface expression of CD44, CD69, and CD62L after a long period of priming and challenges of Mdr2 −/− mice with SPZ. These two subsets of memory T cells were previously reported in an alternative immunization protocol whereby following radiation-attenuated SPZ immunization, the overall population of intrahepatic CD8 T cells significantly increases as compared to naïve mice and protection was linked to both increased CD8 Tem and Tcm (61). In our model, it was striking to observe that 70 days after the last SPZ challenge, in contrast to radiationattenuated SPZ immunization protocol, challenged MDR2 −/− mice only maintained a substantially elevated absolute numbers of CD4 Tcm cells, but not Tcm CD8 cells nor CD8 and CD4 Tem cells.…”

Section: Discussionsupporting

confidence: 54%

Hepatic Inflammation Confers Protective Immunity Against Liver Stages of Malaria Parasite

et al. 2020

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Deciphering the mechanisms by which Plasmodium parasites develop inside hepatocytes is an important step toward the understanding of malaria pathogenesis. We propose that the nature and the magnitude of the inflammatory response in the liver are key for the establishment of the infection. Here, we used mice deficient in the multidrug resistance-2 gene (Mdr2 −/−)-encoded phospholipid flippase leading to the development of liver inflammation. Infection of Mdr2 −/− mice with Plasmodium berghei ANKA (PbANKA) sporozoites (SPZ) resulted in the blockade of hepatic exo-erythrocytic forms (EEFs) with no further development into blood stage parasites. Interestingly, cultured primary hepatocytes from mutant and wild-type mice are equally effective in supporting EEF development. The abortive infection resulted in a long-lasting immunity in Mdr2 −/− mice against infectious SPZ where neutrophils and IL-6 appear as key effector components along with CD8 + and CD4 + effector and central memory T cells. Inflammation-induced breakdown of liver tolerance promotes anti-parasite immunity and provides new approaches for the design of effective vaccines against malaria disease.

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Section: Discussionsupporting

confidence: 54%

Hepatic Inflammation Confers Protective Immunity Against Liver Stages of Malaria Parasite

et al. 2020

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PlasmodiumPreerythrocytic Vaccine Antigens Enhance Sterile Protection in Mice Induced by Circumsporozoite Protein

et al. 2021

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Pre-erythrocytic vaccines prevent malaria by targeting parasites in the clinically silent sporozoite and liver stages and preventing progression to the virulent blood stages. The leading pre-erythrocytic vaccine RTS,S/AS01E (Mosquirix®) entered implementation programs in 2019 and targets the major sporozoite surface antigen called circumsporozoite protein or CSP. However, in phase III clinical trials, RTS,S conferred partial protection with limited durability, indicating a need to improve CSP-based vaccination. Previously, we identified highly expressed liver stage proteins that could potentially be used in combination with CSP and are referred to as pre-erythrocytic vaccine antigens (PEVA). Here, we developed heterologous prime-boost CSP vaccination models to confer partial sterilizing immunity against Plasmodium yoelii (Py)(protein prime/adenovirus 5 (Ad5) boost) and P. berghei (Pb) (DNA prime/Ad5 boost) in mice. When combined as individual antigens with PyCSP, 3 of 8 PyPEVA significantly enhanced sterile protection against sporozoite challenge, compared to PyCSP alone. Similar results were obtained when 3 PbPEVA and PbCSP were combined in a single vaccine regimen. In general, PyCSP antibody responses were similar after CSP alone versus CSP+PEVA vaccinations. Both Py and Pb CSP+PEVA combination vaccines induced robust CD8 + T cell responses including signature IFN-γ increases. In the Pb model system, IFN-γ responses were significantly higher in hepatic than splenic CD8 + T cells. The addition of novel antigens may enhance the degree and duration of sterile protective immunity conferred by a human vaccine such as RTS,S.

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Pre-erythrocytic Immunity in Malaria

Cited by 2 publications

References 56 publications

Hepatic Inflammation Confers Protective Immunity Against Liver Stages of Malaria Parasite

Hepatic Inflammation Confers Protective Immunity Against Liver Stages of Malaria Parasite

PlasmodiumPreerythrocytic Vaccine Antigens Enhance Sterile Protection in Mice Induced by Circumsporozoite Protein

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