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Image courtesy of Ute Frevert
and Margaret Shear
A study published in PLOS Pathogens has revealed proteins that may be viable targets for malaria vaccines.
Investigators identified 42 proteins that can be found on the surface of Plasmodium falciparum sporozoites and could be targeted by vaccines.
However, the team also found evidence to suggest that 2 other surface proteins should not be targeted, as they may be able to evade the immune system.
“We used a method that we developed in a previous paper to identify which proteins of the malaria parasite, Plasmodium falciparum, might be visible to the human immune system on the outside of the parasite and therefore are good potential targets for the development of new malaria vaccines,” said study author Scott E. Lindner, PhD, of Pennsylvania State University in University Park.
“Current experimental malaria vaccines target single proteins and do not provide the level of protection necessary to prevent the spread of the disease. Our new list of potential vaccine targets will allow the development of more effective vaccines that target several proteins on the surface of the parasite.”
To identify these targets, Dr Lindner and his colleagues collected malaria sporozoites from the salivary glands of thousands of infected mosquitoes.
The investigators then marked proteins on the surface of the sporozoites with a chemical label that could not cross through the outer membrane of the parasite. The team identified and characterized the labeled proteins using mass spectrometry.
“We focused on the transmission stage of the parasite because, at this point in an infection, the number of parasites is low, and if we can design effective vaccines for this stage, we can stop the progress of the disease before it causes symptoms,” Dr Lindner said. “Once the parasites are in the liver, they can hide from our immune system by residing inside of liver cells.”
Based on multiple replications of their experiments, the investigators identified 42 proteins that are highly likely to be exposed on the surface of the parasite and are therefore potential targets for vaccines.
The team noted that many of the proteins they identified had been thought to be located exclusively on the inside of the parasite. They suggest that these proteins may become exposed as the parasite moves from the site of a mosquito bite toward the liver.
“Malaria is still one of the great global health issues today, with hundreds of millions of new infections and half a million deaths each year, most of which occur in children under the age of 5,” Dr Lindner said.
“The parasite quickly and efficiently develops resistance to the drugs that we use to treat the disease, so what’s really needed to make eradication of malaria possible is a better vaccine. Our research provides an experimentally validated list of protein targets that could be used to develop new, more effective malaria vaccines.”
The investigators also discovered that 2 surface proteins—CSP and TRAP—are glycosylated in sporozoites, which changes the way the proteins are recognized by the immune system.
The team believes this discovery will affect the way future vaccines are designed as well.
“Our goal was to identify proteins that are present on the surface of sporozoites in hopes of finding targets for new vaccines,” said study author Kristian E. Swearingen, PhD, of the Institute for Systems Biology in Seattle, Washington.
“In addition to the potential new targets we’ve found, we’re also excited about the discovery that 2 of the major sporozoite surface proteins are glycosylated. The presence of sugars on these proteins almost certainly affects the way they are recognized by antibodies, something that will need to be factored in for future vaccine efforts based on these proteins.” 
Image courtesy of Ute Frevert
and Margaret Shear
A study published in PLOS Pathogens has revealed proteins that may be viable targets for malaria vaccines.
Investigators identified 42 proteins that can be found on the surface of Plasmodium falciparum sporozoites and could be targeted by vaccines.
However, the team also found evidence to suggest that 2 other surface proteins should not be targeted, as they may be able to evade the immune system.
“We used a method that we developed in a previous paper to identify which proteins of the malaria parasite, Plasmodium falciparum, might be visible to the human immune system on the outside of the parasite and therefore are good potential targets for the development of new malaria vaccines,” said study author Scott E. Lindner, PhD, of Pennsylvania State University in University Park.
“Current experimental malaria vaccines target single proteins and do not provide the level of protection necessary to prevent the spread of the disease. Our new list of potential vaccine targets will allow the development of more effective vaccines that target several proteins on the surface of the parasite.”
To identify these targets, Dr Lindner and his colleagues collected malaria sporozoites from the salivary glands of thousands of infected mosquitoes.
The investigators then marked proteins on the surface of the sporozoites with a chemical label that could not cross through the outer membrane of the parasite. The team identified and characterized the labeled proteins using mass spectrometry.
“We focused on the transmission stage of the parasite because, at this point in an infection, the number of parasites is low, and if we can design effective vaccines for this stage, we can stop the progress of the disease before it causes symptoms,” Dr Lindner said. “Once the parasites are in the liver, they can hide from our immune system by residing inside of liver cells.”
Based on multiple replications of their experiments, the investigators identified 42 proteins that are highly likely to be exposed on the surface of the parasite and are therefore potential targets for vaccines.
The team noted that many of the proteins they identified had been thought to be located exclusively on the inside of the parasite. They suggest that these proteins may become exposed as the parasite moves from the site of a mosquito bite toward the liver.
“Malaria is still one of the great global health issues today, with hundreds of millions of new infections and half a million deaths each year, most of which occur in children under the age of 5,” Dr Lindner said.
“The parasite quickly and efficiently develops resistance to the drugs that we use to treat the disease, so what’s really needed to make eradication of malaria possible is a better vaccine. Our research provides an experimentally validated list of protein targets that could be used to develop new, more effective malaria vaccines.”
The investigators also discovered that 2 surface proteins—CSP and TRAP—are glycosylated in sporozoites, which changes the way the proteins are recognized by the immune system.
The team believes this discovery will affect the way future vaccines are designed as well.
“Our goal was to identify proteins that are present on the surface of sporozoites in hopes of finding targets for new vaccines,” said study author Kristian E. Swearingen, PhD, of the Institute for Systems Biology in Seattle, Washington.
“In addition to the potential new targets we’ve found, we’re also excited about the discovery that 2 of the major sporozoite surface proteins are glycosylated. The presence of sugars on these proteins almost certainly affects the way they are recognized by antibodies, something that will need to be factored in for future vaccine efforts based on these proteins.”
Image courtesy of Ute Frevert
and Margaret Shear
A study published in PLOS Pathogens has revealed proteins that may be viable targets for malaria vaccines.
Investigators identified 42 proteins that can be found on the surface of Plasmodium falciparum sporozoites and could be targeted by vaccines.
However, the team also found evidence to suggest that 2 other surface proteins should not be targeted, as they may be able to evade the immune system.
“We used a method that we developed in a previous paper to identify which proteins of the malaria parasite, Plasmodium falciparum, might be visible to the human immune system on the outside of the parasite and therefore are good potential targets for the development of new malaria vaccines,” said study author Scott E. Lindner, PhD, of Pennsylvania State University in University Park.
“Current experimental malaria vaccines target single proteins and do not provide the level of protection necessary to prevent the spread of the disease. Our new list of potential vaccine targets will allow the development of more effective vaccines that target several proteins on the surface of the parasite.”
To identify these targets, Dr Lindner and his colleagues collected malaria sporozoites from the salivary glands of thousands of infected mosquitoes.
The investigators then marked proteins on the surface of the sporozoites with a chemical label that could not cross through the outer membrane of the parasite. The team identified and characterized the labeled proteins using mass spectrometry.
“We focused on the transmission stage of the parasite because, at this point in an infection, the number of parasites is low, and if we can design effective vaccines for this stage, we can stop the progress of the disease before it causes symptoms,” Dr Lindner said. “Once the parasites are in the liver, they can hide from our immune system by residing inside of liver cells.”
Based on multiple replications of their experiments, the investigators identified 42 proteins that are highly likely to be exposed on the surface of the parasite and are therefore potential targets for vaccines.
The team noted that many of the proteins they identified had been thought to be located exclusively on the inside of the parasite. They suggest that these proteins may become exposed as the parasite moves from the site of a mosquito bite toward the liver.
“Malaria is still one of the great global health issues today, with hundreds of millions of new infections and half a million deaths each year, most of which occur in children under the age of 5,” Dr Lindner said.
“The parasite quickly and efficiently develops resistance to the drugs that we use to treat the disease, so what’s really needed to make eradication of malaria possible is a better vaccine. Our research provides an experimentally validated list of protein targets that could be used to develop new, more effective malaria vaccines.”
The investigators also discovered that 2 surface proteins—CSP and TRAP—are glycosylated in sporozoites, which changes the way the proteins are recognized by the immune system.
The team believes this discovery will affect the way future vaccines are designed as well.
“Our goal was to identify proteins that are present on the surface of sporozoites in hopes of finding targets for new vaccines,” said study author Kristian E. Swearingen, PhD, of the Institute for Systems Biology in Seattle, Washington.
“In addition to the potential new targets we’ve found, we’re also excited about the discovery that 2 of the major sporozoite surface proteins are glycosylated. The presence of sugars on these proteins almost certainly affects the way they are recognized by antibodies, something that will need to be factored in for future vaccine efforts based on these proteins.”