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

Gert van der Hoek

Gert van der Hoek

In Memoriam - Editor, Senior Moderator
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.

https://www.nature.com/articles/s41467-018-05041-7

Note: in mice.
 
[TABLE="width: 0"]
[TR]
[TD]United States Patent Application[/TD]
[TD]20210030859[/TD]
[/TR]
[TR]
[TD]Kind Code[/TD]
[TD]A1[/TD]
[/TR]
[TR]
[TD]BUCALA; Richard ; et al.[/TD]
[TD]February 4, 2021[/TD]
[/TR]
[/TABLE]
USES OF PARASITE MACROPHAGE MIGRATION INHIBITORY FACTORS

Abstract

This invention relates to compositions (e.g. vaccine compositions) which can be used to provide a subject with protective immunity against a parasite infection.

The compositions comprise: (i) an immunologically effective amount of a nucleic acid (e.g. a nucleic acid-based vaccine) comprising a sequence which encodes a parasite macrophage migration inhibitory factor (MIF) antigen; (ii) a parasite MIF antigen; or (iii) an antibody which specifically binds to a parasite MIF antigen.

The compositions may be used to treat infections and diseases caused by parasitic protozoans, such as a Plasmodium parasite, or parasitic helminths.

http://appft1.uspto.gov/netacgi/nph-...DN/20210030859
 
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