title: Class II-restricted protective immunity induced by malaria sporozoites.
abstract: The irradiated-sporozoite vaccine elicits sterile immunity against Plasmodium parasites in experimental rodent hosts and human volunteers. Based on rodent malaria models, it has been proposed that CD8+ T cells are the key protective effector mechanism required in sporozoite-induced immunity. To investigate the role of class II-restricted immunity in protective immunity, we immunized beta2-microglobulin knockout (beta2M-/-) mice with irradiated Plasmodium yoelii or P. berghei sporozoites. Sterile immunity was obtained in the CD8+-T-cell-deficient mice immunized with either P. berghei or P. yoelii sporozoites. beta2M-/- mice with the BALB/c (H-2d) genetic background as well as those with the C57BL (H-2b) genetic background were protected. Effector mechanisms included CD4+ T cells, mediated in part through the production of gamma interferon, and neutralizing antibodies that targeted the extracellular sporozoites. We conclude that in the absence of class I-restricted CD8+ T cells, sporozoite-induced protective immunity can be effectively mediated by class II-restricted immune effector mechanisms. These results support efforts to develop subunit vaccines that effectively elicit high levels of antibody and CD4+ T cells to target Plasmodium pre-erythrocytic stages.
authors.affiliation: Department of Medical Parasitology, New York University School of Medicine, 341 East 25th St., New York, NY 10010, USA.
authors.forename: Giane A
authors.initials: GA
authors.lastname: Oliveira
authors.forename: Kota Arun
authors.initials: KA
authors.lastname: Kumar
authors.forename: J Mauricio
authors.initials: JM
authors.lastname: Calvo-Calle
authors.forename: Caroline
authors.initials: C
authors.lastname: Othoro
authors.forename: David
authors.initials: D
authors.lastname: Altszuler
authors.forename: Victor
authors.initials: V
authors.lastname: Nussenzweig
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Nardin
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008099:Liver / Q000469:parasitology; D008212:Lymphocyte Depletion; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests; D010962:Plasmodium berghei / Q000276:immunology* / Q000528:radiation effects; D010967:Plasmodium yoelii / Q000276:immunology* / Q000528:radiation effects; D034101:Sporozoites / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency
chemical_list: D000913:Antibodies, Protozoan; D001613:beta 2-Microglobulin; D007371:Interferon-gamma