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Designing a plague vaccine utilizing α-gal modified antigens (52.6)

Yashdeep Phanse, Brenda Carrillo-Conde, Lucas Huntimer, Amanda Ramer-Tait, Bryan Bellaire, Balaji Narasimhan, Ramon Flick, Robert Mandell and Michael Wannemuehler
J Immunol April 1, 2010, 184 (1 Supplement) 52.6;
Yashdeep Phanse
Iowa State University, Ames, IA
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Brenda Carrillo-Conde
Iowa State University, Ames, IA
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Lucas Huntimer
Iowa State University, Ames, IA
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Amanda Ramer-Tait
Iowa State University, Ames, IA
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Bryan Bellaire
Iowa State University, Ames, IA
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Balaji Narasimhan
Iowa State University, Ames, IA
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Ramon Flick
BioProtection Systems, Ames, IA
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Robert Mandell
BioProtection Systems, Ames, IA
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Michael Wannemuehler
Iowa State University, Ames, IA
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Abstract

Background: F1-V from Yersinia pestis has been shown to be a protective antigen against disease. We modified the F1-V antigen with α-galactose residues and immunized α galactosyl transferase (α-GT) KO mice in order to mimic the same defect in humans that results in circulating antibodies against α-gal epitopes enhancing immune responsiveness. Aim: To demonstrate that α-gal modified F1-V induces a more robust immune response than unmodified F1-V. Methods: α-GT KO mice were injected subcutaneously with different doses of α-gal-F1-V or F1-V. All mice were boosted with F1-V at 36 dpi and necropsied on day 40 in order to evaluate in vitro recall response of lymphocytes and to measure anti-F1-V antibody titers. Results: Mean IgG titer values were 50,000 and 10,000 for mice immunized with the α-gal-F1-V or F1-V, respectively. The relative avidity of the antibody response was also higher for the α-gal-F1-V immunized mice. Moreover, lymphocytes from α-gal-F1-V immunized mice demonstrated enhanced proliferation in response to F1-V compared to cells from F1-V immunized mice. Conclusions: α-gal modified F1-V increases both the avidity and amount of anti-F1-V produced following vaccination. As a functional assay, α-gal-F1-V antisera efficiently opsonized Y. pestis, facilitated phagocytosis by human monocytes and prevented Y. pestis-induced monocyte cytotoxicity.

  • Copyright © 2010 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 184, Issue 1 Supplement
April 2010
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Designing a plague vaccine utilizing α-gal modified antigens (52.6)
Yashdeep Phanse, Brenda Carrillo-Conde, Lucas Huntimer, Amanda Ramer-Tait, Bryan Bellaire, Balaji Narasimhan, Ramon Flick, Robert Mandell, Michael Wannemuehler
The Journal of Immunology April 1, 2010, 184 (1 Supplement) 52.6;

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Designing a plague vaccine utilizing α-gal modified antigens (52.6)
Yashdeep Phanse, Brenda Carrillo-Conde, Lucas Huntimer, Amanda Ramer-Tait, Bryan Bellaire, Balaji Narasimhan, Ramon Flick, Robert Mandell, Michael Wannemuehler
The Journal of Immunology April 1, 2010, 184 (1 Supplement) 52.6;
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Print ISSN 0022-1767        Online ISSN 1550-6606