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

Research output: Contribution to JournalArticleAcademicpeer-review


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 languageEnglish
Article numberPMID: 30006528
Number of pages13
JournalNature Communications
Issue number2714
Publication statusPublished - 13 Jul 2018


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.

FundersFunder number
Novartis Vaccines, Inc.
National Institutes of HealthAI 5R01-51306-05, AI 2R01-042310-12
National Institute of Allergy and Infectious DiseasesR01AI110452
Deutsche ForschungsgemeinschaftSFB1123/A03


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