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An RNA replicon-based vaccine can fight malaria infection in mice, according to research published in Nature Communications.
The vaccine targets a protein, Plasmodium macrophage migration inhibitory factor (PMIF), which is produced by malaria parasites and suppresses memory T cells.
The vaccine provided improved control of existing malaria infection as well as protection from reinfection in mice.
This work was funded by National Institutes of Health grants and Novartis Vaccines, Inc.
The research began with a strain of Plasmodium berghei in which PMIF was genetically deleted. Investigators found that mice infected with this strain developed memory T cells and showed stronger anti-parasite immunity.
This led the researchers to test a vaccine targeting PMIF in 2 mouse models of malaria. One model was an early stage liver infection, and the other was a severe, late-stage blood infection.
The vaccine reduced parasitemia in both models and prolonged survival in mice with the late-stage blood infection.
The investigators then cured vaccinated mice of malaria (via treatment with chloroquine) and reinfected them.
Mice reinfected with late-stage malaria had no evidence of parasites in the blood or organs after reinfection.
The mice reinfected with liver-stage malaria had a 70% reduction in liver parasites (compared to control mice) upon reinfection, and they did not develop blood-stage infection.
“If you vaccinate with this specific protein used by the malaria parasite to evade an immune response, you can elicit protection against reinfection,” said study author Richard Bucala, MD, of Yale School of Medicine in New Haven, Connecticut.
“To our knowledge, this has never been shown using a single antigen in fulminant blood-stage infection.”
The researchers also transferred memory T cells from immunized mice to naïve mice that had never been exposed to malaria. The T-cell recipients were completely protected from malaria infection.
The investigators’ next step with this work is to develop a vaccine for humans who have never had malaria, primarily young children.
“The vaccine would be used in children so that they would already have an immune response to this particular malaria product, and when they became infected with malaria, they would have a normal T-cell response, clear the parasite, and be protected from future infection,” Dr Bucala said.
An RNA replicon-based vaccine can fight malaria infection in mice, according to research published in Nature Communications.
The vaccine targets a protein, Plasmodium macrophage migration inhibitory factor (PMIF), which is produced by malaria parasites and suppresses memory T cells.
The vaccine provided improved control of existing malaria infection as well as protection from reinfection in mice.
This work was funded by National Institutes of Health grants and Novartis Vaccines, Inc.
The research began with a strain of Plasmodium berghei in which PMIF was genetically deleted. Investigators found that mice infected with this strain developed memory T cells and showed stronger anti-parasite immunity.
This led the researchers to test a vaccine targeting PMIF in 2 mouse models of malaria. One model was an early stage liver infection, and the other was a severe, late-stage blood infection.
The vaccine reduced parasitemia in both models and prolonged survival in mice with the late-stage blood infection.
The investigators then cured vaccinated mice of malaria (via treatment with chloroquine) and reinfected them.
Mice reinfected with late-stage malaria had no evidence of parasites in the blood or organs after reinfection.
The mice reinfected with liver-stage malaria had a 70% reduction in liver parasites (compared to control mice) upon reinfection, and they did not develop blood-stage infection.
“If you vaccinate with this specific protein used by the malaria parasite to evade an immune response, you can elicit protection against reinfection,” said study author Richard Bucala, MD, of Yale School of Medicine in New Haven, Connecticut.
“To our knowledge, this has never been shown using a single antigen in fulminant blood-stage infection.”
The researchers also transferred memory T cells from immunized mice to naïve mice that had never been exposed to malaria. The T-cell recipients were completely protected from malaria infection.
The investigators’ next step with this work is to develop a vaccine for humans who have never had malaria, primarily young children.
“The vaccine would be used in children so that they would already have an immune response to this particular malaria product, and when they became infected with malaria, they would have a normal T-cell response, clear the parasite, and be protected from future infection,” Dr Bucala said.
An RNA replicon-based vaccine can fight malaria infection in mice, according to research published in Nature Communications.
The vaccine targets a protein, Plasmodium macrophage migration inhibitory factor (PMIF), which is produced by malaria parasites and suppresses memory T cells.
The vaccine provided improved control of existing malaria infection as well as protection from reinfection in mice.
This work was funded by National Institutes of Health grants and Novartis Vaccines, Inc.
The research began with a strain of Plasmodium berghei in which PMIF was genetically deleted. Investigators found that mice infected with this strain developed memory T cells and showed stronger anti-parasite immunity.
This led the researchers to test a vaccine targeting PMIF in 2 mouse models of malaria. One model was an early stage liver infection, and the other was a severe, late-stage blood infection.
The vaccine reduced parasitemia in both models and prolonged survival in mice with the late-stage blood infection.
The investigators then cured vaccinated mice of malaria (via treatment with chloroquine) and reinfected them.
Mice reinfected with late-stage malaria had no evidence of parasites in the blood or organs after reinfection.
The mice reinfected with liver-stage malaria had a 70% reduction in liver parasites (compared to control mice) upon reinfection, and they did not develop blood-stage infection.
“If you vaccinate with this specific protein used by the malaria parasite to evade an immune response, you can elicit protection against reinfection,” said study author Richard Bucala, MD, of Yale School of Medicine in New Haven, Connecticut.
“To our knowledge, this has never been shown using a single antigen in fulminant blood-stage infection.”
The researchers also transferred memory T cells from immunized mice to naïve mice that had never been exposed to malaria. The T-cell recipients were completely protected from malaria infection.
The investigators’ next step with this work is to develop a vaccine for humans who have never had malaria, primarily young children.
“The vaccine would be used in children so that they would already have an immune response to this particular malaria product, and when they became infected with malaria, they would have a normal T-cell response, clear the parasite, and be protected from future infection,” Dr Bucala said.