title: CD8 T cell independent immunity after single dose infection-treatment-vaccination (ITV) against Plasmodium yoelii.
abstract: Sporozoite vaccination of both humans and rodents elicits potent anti-malarial immunity, but the dose of sporozoites and the number of immunizations required varies with vaccination approach. Here we examine the immunological basis for superior protection afforded from single-dose vaccination with virulent sporozoites administered under prophylatic chloroquine-cover, referred to as infection-treatment-vaccination (ITV), compared to the well-studied approach of administering radiation-attenuated Plasmodium sporozoites (RAS). Earlier rodent studies utilizing ITV and RAS vaccination suggested a major role of CD8 T cells in reducing liver parasite burden after sporozoite challenge in a BALB/c mouse model. Consistent with this, we find that in C57Bl/6 mice ITV elicits substantially higher parasite-specific CD8 T cell responses than RAS vaccination and enhances immunity against P. yoelii infection. However, we show ITV-induced CD8 T cells are not necessary for protection following liver-stage sporozoite or blood-stage parasite challenge. Mechanistically, we found protection afforded from single-dose ITV is associated with low grade, transient parasitemia shortly following cessation of chloroquine treatment and generation of potent antibody responses to blood-stage parasites. Collectively, our data show the mechanistic basis for enhanced protective immunity against P. yoelli elicited by ITV in highly susceptible C57Bl/6 mice is independent of CD8 T cells. These studies may be relevant in understanding the potent immunity observed with ITV in humans.
authors: Department of Microbiology, University of Iowa, Iowa City, IA, USA.
authors: Katherine L
authors: KL
authors: Doll
authors: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Noah S
authors: NS
authors: Butler
authors: Department of Microbiology, University of Iowa, Iowa City, IA, USA; Department of Pathology, University of Iowa, Iowa City, IA, USA; Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA, USA. Electronic address: john-harty@uiowa.edu.
authors: John T
authors: JT
authors: Harty
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000962:Antimalarials / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002738:Chloroquine / Q000627:therapeutic use; D005260:Female; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000517:prevention & control; D010967:Plasmodium yoelii; D034101:Sporozoites / Q000276:immunology; D014613:Vaccines, Attenuated / Q000627:therapeutic use
chemical_list: D000913:Antibodies, Protozoan; D000962:Antimalarials; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated; D002738:Chloroquine
keywords: Antibodies; B6; C57Bl/6; CD8 T cells; CQ; GAP; ITV; Plasmodium infections; Plasmodium yoelii 17XNL; Py; RAS; RBC; Subpatent infection; Vaccination; chloroquine; genetically attenuated parasites; infection-treatment vaccination; radiation-attenuated sporozoites; red blood cell