Vaccination with live Plasmodium yoelii blood stage parasites under chloroquine cover induces cross-stage immunity against malaria liver stage.
Immunity to malaria has long been thought to be stage-specific. In this study we show that immunization of BALB/c mice with live erythrocytes infected with nonlethal strains of Plasmodium yoelii under curative chloroquine cover conferred protection not only against challenge by blood stage parasites but also against sporozoite challenge. This cross-stage protection was dose-dependent and long lasting. CD4(+) and CD8(+) T cells inhibited malaria liver but not blood stage. Their effect was mediated partially by IFN-gamma, and was completely dependent of NO. Abs against both pre-erythrocytic and blood parasites were elicited and were essential for protection against blood stage and liver stage parasites. Our results suggest that Ags shared by liver and blood stage parasites can be the foundation for a malaria vaccine that would provide effective protection against both pre-erythrocytic and erythrocytic asexual parasites found in the mammalian host.
Belnoue
Elodie
E
Department of Immunology, Centre National de la Recherche Scientifique, Institut Cochin, Université Paris Descartes, Paris, France.
Voza
Tatiana
T
Costa
Fabio T M
FT
Grüner
Anne Charlotte
AC
Mauduit
Marjorie
M
Rosa
Daniela Santoro
DS
Depinay
Nadya
N
Kayibanda
Michèle
M
Vigário
Ana Margarida
AM
Mazier
Dominique
D
Snounou
Georges
G
Sinnis
Photini
P
Rénia
Laurent
L
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D002738:Chloroquine / Q000008:administration & dosage*; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology*; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D008109:Liver Diseases, Parasitic / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D008288:Malaria / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology*; D034101:Sporozoites / Q000187:drug effects / Q000254:growth & development / Q000276:immunology
D000962:Antimalarials; D017780:Malaria Vaccines; D002738:Chloroquine