Complete protection against P. berghei malaria upon heterologous prime/boost immunization against circumsporozoite protein employing Salmonella type III secretion system and Bordetella adenylate cyclase toxoid.
Sterile immunity against malaria can be achieved by the induction of IFNgamma-producing CD8(+) T cells that target infected hepatocytes presenting epitopes of the circumsporozoite protein (CSP). In the present study we evaluate the protective efficacy of a heterologous prime/boost immunization protocol based on the delivery of the CD8(+) epitope of Plasmodium berghei CSP into the MHC class I presentation pathway, by either a type III secretion system of live recombinant Salmonella and/or by direct translocation of a recombinant Bordetella adenylate cyclase toxoid fusion (ACT-CSP) into the cytosol of professional antigen-presenting cells (APCs). A single intraperitoneal application of the recombinant ACT-CSP toxoid, as well as a single oral immunization with the Salmonella vaccine, induced a specific CD8(+) T cell response, which however conferred only a partial protection on mice against a subsequent sporozoite challenge. In contrast, a heterologous prime/boost vaccination with the live Salmonella followed by ACT-CSP led to a significant enhancement of the CSP-specific T cell response and induced complete protection in all vaccinated mice.
Tartz
Susanne
S
Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. tartz@bni.uni-hamburg.de
Rüssmann
Holger
H
Kamanova
Jana
J
Sebo
Peter
P
Sturm
Angelika
A
Heussler
Volker
V
Fleischer
Bernhard
B
Jacobs
Thomas
T
D037361:Adenylate Cyclase Toxin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001884:Bordetella / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D007114:Immunization; D007117:Immunization, Secondary; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D037361:Adenylate Cyclase Toxin; D001426:Bacterial Proteins; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C041595:circumsporozoite protein, Protozoan