The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites.
Malaria infection starts when mosquitoes inject sporozoites into the skin. The parasites enter the blood stream and make their way to the liver where they develop into the exo-erythrocytic forms (EEFs). Immunization with irradiated sporozoites (IrSp) leads to robust protection against malaria infection in rodents, monkeys and humans by eliciting antibodies to circumsporozoite protein (CS) that inhibit sporozoite infectivity, and T cells that destroy the EEFs. To study the role of non-CS antigens in protection, we produced CS transgenic mice that were tolerant to CS T-cell epitopes. Here we show that in the absence of T-cell-dependent immune responses to CS, protection induced by immunization with two doses of IrSp was greatly reduced. Thus, although hundreds of other Plasmodium genes are expressed in sporozoites and EEFs, CS is a dominant protective antigen. Nevertheless, sterile immunity could be obtained by immunization of CS transgenics with three doses of IrSp.
Kumar
Kota Arun
KA
Michael Heidelberger Division of Immunology, Department of Pathology, New York University School of Medicine, New York, New York 10016, USA. arun.kumar@med.nyu.edu
Sano
Gen-ichiro
G
Boscardin
Silvia
S
Nussenzweig
Ruth S
RS
Nussenzweig
Michel C
MC
Zavala
Fidel
F
Nussenzweig
Victor
V
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015800:Protozoan Proteins / Q000276:immunology*; D034101:Sporozoites / Q000737:chemistry / Q000276:immunology* / Q000528:radiation effects*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000953:Antigens, Protozoan; D016056:Immunodominant Epitopes; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan