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Immunogenicity and protective efficacy of a recombinant yellow fever vaccine against the murine malarial parasite Plasmodium yoelii
Authors:Cristina T. Stoyanov  Silvia B. Boscardin  Stephanie Deroubaix  Giovanna Barba-Spaeth  David Franco  Ruth S. Nussenzweig  Michel Nussenzweig  Charles M. Rice
Affiliation:1. Laboratory of Virology and Infectious Disease, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA;2. Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA;3. Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA;4. Department of Medical and Molecular Parasitology, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
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-γ by CD8+ T-cells and IFN-γ 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.
Keywords:YF17D   Malaria   Protection
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