title: Cutting edge: attrition of Plasmodium-specific memory CD8 T cells results in decreased protection that is rescued by booster immunization.
abstract: Sterile protection against infection with Plasmodium sporozoites requires high numbers of memory CD8 T cells. However, infections with unrelated pathogens, as may occur in areas endemic to malaria, can dramatically decrease pre-existing memory CD8 T cells. It remains unknown whether unrelated infections will compromise numbers of Plasmodium-specific memory CD8 T cells and thus limit the duration of antimalarial immunity generated by subunit vaccination. We show that P. berghei circumsporozoite-specific memory CD8 T cells underwent significant attrition in numbers in mice subjected to unrelated infections. Attrition was associated with preferential loss of effector memory CD8 T cells and reduced immunity to P. berghei sporozoite challenge. However, and of relevance to deployment of Plasmodium vaccines in areas endemic to malaria, attrition of memory CD8 T cells was reversed by booster immunization, which restored protection. These data suggest that regular booster immunizations may be required to sustain protective vaccine-induced Plasmodium-specific memory CD8 T cells in the face of attrition caused by unrelated infections.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Schmidt
authors.forename: John T
authors.initials: JT
authors.lastname: Harty
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D018352:Coronavirus Infections / Q000276:immunology / Q000517:prevention & control; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D007113:Immunity, Innate; D007117:Immunization, Secondary / Q000379:methods; D007156:Immunologic Memory; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control; D008212:Lymphocyte Depletion / Q000379:methods; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000517:prevention & control; D008288:Malaria / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control
chemical_list: D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan