Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection

Alvaro Baeza Garcia, Edwin Siu, Tiffany Sun, Valerie Exler, Luis Brito, Armin Hekele, Gib Otten, Kevin Augustijn, Chris J. Janse, Jeffrey B. Ulmer, Jürgen Bernhagen, Erol Fikrig, Andrew Geall and Richard Bucala ()
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Alvaro Baeza Garcia: Yale School of Medicine
Edwin Siu: Yale School of Medicine
Tiffany Sun: Yale School of Medicine
Valerie Exler: Yale School of Medicine
Luis Brito: Novartis Vaccines, Inc.
Armin Hekele: Novartis Vaccines, Inc.
Gib Otten: Novartis Vaccines, Inc.
Kevin Augustijn: Leiden University Medical Centre
Chris J. Janse: Leiden University Medical Centre
Jeffrey B. Ulmer: Novartis Vaccines, Inc.
Jürgen Bernhagen: Klinikum der Universität München Ludwig-Maximilians-Universität München
Erol Fikrig: Yale University School of Medicine
Andrew Geall: Novartis Vaccines, Inc.
Richard Bucala: Yale School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Plasmodium species produce an ortholog of the cytokine macrophage migration inhibitory factor, PMIF, which modulates the host inflammatory response to malaria. Using a novel RNA replicon-based vaccine, we show the impact of PMIF immunoneutralization on the host response and observed improved control of liver and blood-stage Plasmodium infection, and complete protection from re-infection. Vaccination against PMIF delayed blood-stage patency after sporozoite infection, reduced the expression of the Th1-associated inflammatory markers TNF-α, IL-12, and IFN-γ during blood-stage infection, augmented Tfh cell and germinal center responses, increased anti-Plasmodium antibody titers, and enhanced the differentiation of antigen-experienced memory CD4 T cells and liver-resident CD8 T cells. Protection from re-infection was recapitulated by the adoptive transfer of CD8 or CD4 T cells from PMIF RNA immunized hosts. Parasite MIF inhibition may be a useful approach to promote immunity to Plasmodium and potentially other parasite genera that produce MIF orthologous proteins.

Date: 2018
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DOI: 10.1038/s41467-018-05041-7

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