title: Immunogenicity and protective efficacy of a recombinant yellow fever vaccine against the murine malarial parasite Plasmodium yoelii.
abstract: The live-attenuated yellow fever vaccine (YF17D) is one of the safest and most effective vaccines available today. Here, YF17D was genetically altered to express the circumsporozoite protein (CSP) from the murine malarial parasite Plasmodium yoelii. Reconstituted recombinant virus was viable and exhibited robust CSP expression. Immunization of naïve mice resulted in extensive proliferation of adoptively transferred CSP-specific transgenic CD8(+) T-cells. A single immunization of naïve mice with recombinant YF17D resulted in robust production of IFN-gamma by CD8(+) T-cells and IFN-gamma and IL-2 by CD4(+) T-cells. A prime-boost regimen consisting of recombinant virus followed by a low-dose of irradiated sporozoites conferred protection against challenge with P. yoelii. Taken together, these results show that recombinant YF17D can efficiently express CSP in culture, and prime a protective immune response in vivo.
authors.affiliation: Laboratory of Virology and Infectious Disease, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
authors.forename: Cristina T
authors.initials: CT
authors.lastname: Stoyanov
authors.forename: Silvia B
authors.initials: SB
authors.lastname: Boscardin
authors.forename: Stephanie
authors.initials: S
authors.lastname: Deroubaix
authors.forename: Giovanna
authors.initials: G
authors.lastname: Barba-Spaeth
authors.forename: David
authors.initials: D
authors.lastname: Franco
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Nussenzweig
authors.forename: Michel
authors.initials: M
authors.lastname: Nussenzweig
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010957:Plasmids; D010967:Plasmodium yoelii / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology; D022341:Yellow Fever Vaccine / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014613:Vaccines, Attenuated; D022341:Yellow Fever Vaccine; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma
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