title: Reduced Plasmodium berghei sporozoite liver load associates with low protective efficacy after intradermal immunization.
abstract: Studies in animal models suggest that protection against malaria induced by intradermal (ID) administration of sporozoites is less effective compared to intravenous injection (IV). We investigated in a murine model the protective efficacy and immune responses after ID or IV immunization of sporozoites. Mice were immunized via either IV or ID route with Plasmodium berghei sporozoites in combination with chloroquine treatment (CPS) (allowing full liver stage development) or by γ-radiation-attenuated sporozoites (RAS) (early liver stage arrest). While IV immunization with both RAS and CPS generated 90-100% protection, ID immunization resulted in reduced levels of protection with either immunization strategy in both Balb/cByJ (50%) and C57BL/6j mice (7-13%). Lower protection by ID routing associated with a 30-fold lower parasite liver load [P < 0.001 (χ(2) = 49.08, d.f. = 1)] assessed by real-time in vivo imaging of bioluminescent P. berghei parasites. Unlike IV, ID immunization did not result in expansion of CD8+ T cells with effector memory phenotype and showed lower IFNγ responses irrespective of the immunization regime. In conclusion, protection against sporozoite infection is likely dependent on parasite liver infection and subsequently generated cellular immune responses.
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Nganou-Makamdop
authors.forename: I
authors.initials: I
authors.lastname: Ploemen
authors.forename: M
authors.initials: M
authors.lastname: Behet
authors.forename: G-J
authors.initials: GJ
authors.lastname: Van Gemert
authors.forename: C
authors.initials: C
authors.lastname: Hermsen
authors.forename: M
authors.initials: M
authors.lastname: Roestenberg
authors.forename: R W
authors.initials: RW
authors.lastname: Sauerwein
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002738:Chloroquine / Q000008:administration & dosage; D004195:Disease Models, Animal; D005720:Gamma Rays; D007114:Immunization / Q000379:methods; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000276:immunology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D059208:Parasite Load; D010962:Plasmodium berghei / Q000276:immunology* / Q000472:pathogenicity; D034101:Sporozoites / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000962:Antimalarials; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma; D002738:Chloroquine