Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection
Open accessAbstract
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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Two 15 μg primer-booster doses of a squalene-based cationic nanoemulsion loaded with self-amplifying mRNA encoding PMIF improved helper T cell development and elicited anti-Plasmodium IgG antibodies and memory T cell responses.
“Two 15 µg primer–booster doses improved helper T cell development and elicited anti-Plasmodium IgG antibodies and memory T cell responses192.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [192]
Adoptive transfer of T cells from vaccinated mice protected unvaccinated mice from Plasmodium sporozoites.
“Moreover, adoptive transfer of T cells from vaccinated mice protected unvaccinated mice from Plasmodium sporozoites192.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [192]
Lipid nanoparticle-mRNA vaccines have been reported to induce immune protection against parasitical and bacterial infections.
“Apart from viral infections, lipid nanoparticle–mRNA vaccines have been reported to induce immune protection against parasitical31 and bacterial30,198 infections.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [31]
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- Authors
- Baeza Garcia, A., Siu, E., Sun, T., Exler, V., Brito, L., Hekele, A., Otten, G., Augustijn, K., Janse, C. J., Ulmer, J. B., Bernhagen, J., Fikrig, E., Geall, A., & Bucala, R.
- Affiliations
- Yale University (US)
- LMU Klinikum (DE)
- Novartis (United States) (US)
- Leiden University Medical Center (NL)
- GlaxoSmithKline (United States) (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Bucala, Richard
- Venue
- Nature Communications
- Published
- 2018-07-13
- Volume
- 9
- Issue
- 1
- Pages
- 2714-2714
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6045615
- OpenAlex
- W2820610048
- Cited by
- 97
- References
- 43
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 16 · 2023: 13 · 2022: 16 · 2021: 21 · 2020: 8 · 2019: 10
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by)
- RWTH Publications (RWTH Aachen)
- Funders
- Deutsche Forschungsgemeinschaft (SFB1123, SFB1123-A03)
- National Institutes of Health (AI 5R01‐51306‐05)
- National Institute of Allergy and Infectious Diseases (R01AI110452)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- Plasmodium, macrophage migration inhibitory factor, malaria vaccine, protective immunity, blood-stage infection, liver stage infection, T follicular helper cells, germinal center reaction, memory CD4+ T cells, CD8+ T cells, adoptive T cell therapy, host-parasite interactions
- MeSH terms
- Animals, Antibodies, Protozoan, Female, Immunologic Memory, Interferon-gamma, Macrophage Migration-Inhibitory Factors, Malaria, Mice, Inbred BALB C, Plasmodium berghei, Tumor Necrosis Factor-alpha, CD4-Positive T-Lymphocytes, Protozoan Proteins, Gene Expression, RNA, Protozoan, Malaria Vaccines, CD8-Positive T-Lymphocytes, Interleukin-12, Germinal Center, Adoptive Transfer, Vaccines, DNA, Protein Isoforms, Mice, Adaptive Immunity
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