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

Alvaro Baeza Garcia; Edwin Siu; Tiffany Sun; Valerie Exler; Lius Brito; Armin Hekele; Gib Otten; K.D. Augustijn; Chris Janse; Jeffrey Ulmer; Jurgen Bernhagen; Erol Fikrig; Andrew Geall; Richard Bucala

doi:10.1038/s41467-018-05041-7

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

Alvaro Baeza Garcia, Edwin Siu, Tiffany Sun, Valerie Exler, Lius Brito, Armin Hekele, Gib Otten, K.D. Augustijn, Chris Janse, Jeffrey Ulmer, Jurgen Bernhagen, Erol Fikrig, Andrew Geall, Richard Bucala

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Research output: Contribution to Journal › Article › Academic › peer-review

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.

Original language	English
Article number	PMID: 30006528
Number of pages	13
Journal	Nature Communications
Volume	9
Issue number	2714
DOIs	https://doi.org/10.1038/s41467-018-05041-7
Publication status	Published - 13 Jul 2018

Funding

This work was funded by National Institutes of Health Grants AI 5R01-51306-05, AI 2R01-042310-12, and Novartis Vaccines, Inc. This study was supported by the Deutsche Forschungsgemeinschaft grant SFB1123/A03 to J.B. We thank Michelle Chan and Nisha Chandler for coordinating the delivery of formulations for the animal studies. We thank MR4 for providing us with malaria parasites provided by Mark F. Wisser, Andy Waters, and Victor Nussenzweig.

Funders	Funder number
Novartis Vaccines, Inc.
National Institutes of Health	AI 5R01-51306-05, AI 2R01-042310-12
National Institute of Allergy and Infectious Diseases	R01AI110452
Deutsche Forschungsgemeinschaft	SFB1123/A03

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Baeza Garcia, A., Siu, E., Sun, T., Exler, V., Brito, L., Hekele, A., Otten, G., Augustijn, K. D., Janse, C., Ulmer, J., Bernhagen, J., Fikrig, E., Geall, A., & Bucala, R. (2018). Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection. Nature Communications, 9(2714), Article PMID: 30006528. https://doi.org/10.1038/s41467-018-05041-7

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title = "Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection.",

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.",

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Baeza Garcia, A, Siu, E, Sun, T, Exler, V, Brito, L, Hekele, A, Otten, G, Augustijn, KD, Janse, C, Ulmer, J, Bernhagen, J, Fikrig, E, Geall, A & Bucala, R 2018, 'Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection.', Nature Communications, vol. 9, no. 2714, PMID: 30006528. https://doi.org/10.1038/s41467-018-05041-7

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AU - Siu, Edwin

AU - Sun, Tiffany

AU - Exler, Valerie

AU - Brito, Lius

AU - Hekele, Armin

AU - Otten, Gib

AU - Augustijn, K.D.

AU - Janse, Chris

AU - Ulmer, Jeffrey

AU - Bernhagen, Jurgen

AU - Fikrig, Erol

AU - Geall, Andrew

AU - Bucala, Richard

PY - 2018/7/13

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

Abstract

Funding

UN SDGs

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