Protective T cell immunity against malaria liver stage after vaccination with live sporozoites under chloroquine treatment.
In this study we present the first systematic analysis of the immunity induced by normal Plasmodium yoelii sporozoites in mice. Immunization with sporozoites, which was conducted under chloroquine treatment to minimize the influence of blood stage parasites, induced a strong protection against a subsequent sporozoite and, to a lesser extent, against infected RBC challenges. The protection induced by this immunization protocol proved to be very effective. Induction of this protective immunity depended on the presence of liver stage parasites, as primaquine treatment concurrent with sporozoite immunization abrogated protection. Protection was not found to be mediated by the Abs elicited against pre-erythrocytic and blood stage parasites, as demonstrated by inhibition assays of sporozoite penetration or development in vitro and in vivo assays of sporozoite infectivity or blood stage parasite development. CD4(+) and CD8(+) T cells were, however, responsible for the protection through the induction of IFN-gamma and NO.
Belnoue
Elodie
E
Department of Immunology, Institut National de la Santé et de la Recherche Médicale, Unité 567, Centre National de la Recherche Scientifique, Université René Descartes, Hôpital Cochin, Paris, France.
Costa
Fabio T M
FT
Frankenberg
Tobias
T
Vigário
Ana Margarida
AM
Voza
Tatiana
T
Leroy
Nicolas
N
Rodrigues
Mauricio M
MM
Landau
Irène
I
Snounou
Georges
G
Rénia
Laurent
L
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D002738:Chloroquine / Q000008:administration & dosage*; D005260:Female; D006239:Haplotypes; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000502:physiology; D008109:Liver Diseases, Parasitic / Q000188:drug therapy* / Q000276:immunology* / Q000517:prevention & control; D008288:Malaria / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology; D010967:Plasmodium yoelii / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D013045:Species Specificity; D034101:Sporozoites / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology
D000962:Antimalarials; D017780:Malaria Vaccines; D009569:Nitric Oxide; D007371:Interferon-gamma; D002738:Chloroquine