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Credit: St Jude Children’s
Research Hospital
Investigators have identified antibodies that prevent malaria-causing parasites at the schizont stage from rupturing and spilling into the bloodstream.
These antibodies reduced loads of the parasite significantly in mice and humans, and they might one day be exploited to create a malaria vaccine, according to the researchers.
Jonathan Kurtis, MD, PhD, of Rhode Island Hospital in Providence, and his colleagues described the antibodies and their effects in Science.
The investigators studied the plasma of malaria-resistant 2-year-olds in Tanzania, where the disease is endemic. The team thought the naturally acquired immunity in these chronically exposed individuals provided a good model through which to identify vaccine antigens.
The analysis revealed that a particular Plasmodium falciparum antigen, known as P falciparum schizont egress antigen-1 (PfSEA-1), triggered antibodies in the children that, in turn, blocked replication of the parasite.
When the researchers vaccinated malaria-infected mice with the antigen or passively transferred PfSEA-1 antibodies to the rodents, they observed a 4-fold reduction of malaria parasites in the animals’ blood.
“When my post-doctoral fellow, Dipak Raj, discovered that antibodies to this protein, PfSEA-1, effectively trapped the malaria-causing parasite within the red blood cells, it was truly a moment of discovery,” Dr Kurtis said.
“Many researchers are trying to find ways to develop a malaria vaccine by preventing the parasite from entering the red blood cell, and, here, we found a way to block it from leaving the cell once it has entered. If it’s trapped in the red blood cell, it can’t go anywhere. It can’t do any further damage.”
The presence of PfSEA-1 antibodies also appeared to protect the Tanzanian study participants from severe cases of malaria. The investigators measured antibodies to PfSEA-1 in the entire cohort of 785 children and found that, among those with antibodies to PfSEA-1, there were no cases of severe malaria.
To generalize their results, the researchers then went back to serum samples they had collected from 140 children in Kenya in 1997. Analyses revealed that individuals with antibodies to PfSEA-1 had 50% lower parasitemia than individuals without these antibodies during a high-transmission season.
The investigators believe these findings could bring researchers a step closer to an effective malaria vaccine that targets parasites at multiple life stages.
“We still have additional trials ahead of us, first in another animal model, but we hope to begin phase 1 trials in humans very soon,” Dr Kurtis said.
“Our findings support PfSEA-1 as a potential vaccine candidate. And we are confident that, by partnering with our colleagues at the National Institutes of Health and other researchers focused on vaccines to prevent the parasites from entering red blood cells, we can approach the parasite from all angles, which could help us develop a truly effective vaccine to prevent this infectious disease that kills millions of children every year.” 
Credit: St Jude Children’s
Research Hospital
Investigators have identified antibodies that prevent malaria-causing parasites at the schizont stage from rupturing and spilling into the bloodstream.
These antibodies reduced loads of the parasite significantly in mice and humans, and they might one day be exploited to create a malaria vaccine, according to the researchers.
Jonathan Kurtis, MD, PhD, of Rhode Island Hospital in Providence, and his colleagues described the antibodies and their effects in Science.
The investigators studied the plasma of malaria-resistant 2-year-olds in Tanzania, where the disease is endemic. The team thought the naturally acquired immunity in these chronically exposed individuals provided a good model through which to identify vaccine antigens.
The analysis revealed that a particular Plasmodium falciparum antigen, known as P falciparum schizont egress antigen-1 (PfSEA-1), triggered antibodies in the children that, in turn, blocked replication of the parasite.
When the researchers vaccinated malaria-infected mice with the antigen or passively transferred PfSEA-1 antibodies to the rodents, they observed a 4-fold reduction of malaria parasites in the animals’ blood.
“When my post-doctoral fellow, Dipak Raj, discovered that antibodies to this protein, PfSEA-1, effectively trapped the malaria-causing parasite within the red blood cells, it was truly a moment of discovery,” Dr Kurtis said.
“Many researchers are trying to find ways to develop a malaria vaccine by preventing the parasite from entering the red blood cell, and, here, we found a way to block it from leaving the cell once it has entered. If it’s trapped in the red blood cell, it can’t go anywhere. It can’t do any further damage.”
The presence of PfSEA-1 antibodies also appeared to protect the Tanzanian study participants from severe cases of malaria. The investigators measured antibodies to PfSEA-1 in the entire cohort of 785 children and found that, among those with antibodies to PfSEA-1, there were no cases of severe malaria.
To generalize their results, the researchers then went back to serum samples they had collected from 140 children in Kenya in 1997. Analyses revealed that individuals with antibodies to PfSEA-1 had 50% lower parasitemia than individuals without these antibodies during a high-transmission season.
The investigators believe these findings could bring researchers a step closer to an effective malaria vaccine that targets parasites at multiple life stages.
“We still have additional trials ahead of us, first in another animal model, but we hope to begin phase 1 trials in humans very soon,” Dr Kurtis said.
“Our findings support PfSEA-1 as a potential vaccine candidate. And we are confident that, by partnering with our colleagues at the National Institutes of Health and other researchers focused on vaccines to prevent the parasites from entering red blood cells, we can approach the parasite from all angles, which could help us develop a truly effective vaccine to prevent this infectious disease that kills millions of children every year.”
Credit: St Jude Children’s
Research Hospital
Investigators have identified antibodies that prevent malaria-causing parasites at the schizont stage from rupturing and spilling into the bloodstream.
These antibodies reduced loads of the parasite significantly in mice and humans, and they might one day be exploited to create a malaria vaccine, according to the researchers.
Jonathan Kurtis, MD, PhD, of Rhode Island Hospital in Providence, and his colleagues described the antibodies and their effects in Science.
The investigators studied the plasma of malaria-resistant 2-year-olds in Tanzania, where the disease is endemic. The team thought the naturally acquired immunity in these chronically exposed individuals provided a good model through which to identify vaccine antigens.
The analysis revealed that a particular Plasmodium falciparum antigen, known as P falciparum schizont egress antigen-1 (PfSEA-1), triggered antibodies in the children that, in turn, blocked replication of the parasite.
When the researchers vaccinated malaria-infected mice with the antigen or passively transferred PfSEA-1 antibodies to the rodents, they observed a 4-fold reduction of malaria parasites in the animals’ blood.
“When my post-doctoral fellow, Dipak Raj, discovered that antibodies to this protein, PfSEA-1, effectively trapped the malaria-causing parasite within the red blood cells, it was truly a moment of discovery,” Dr Kurtis said.
“Many researchers are trying to find ways to develop a malaria vaccine by preventing the parasite from entering the red blood cell, and, here, we found a way to block it from leaving the cell once it has entered. If it’s trapped in the red blood cell, it can’t go anywhere. It can’t do any further damage.”
The presence of PfSEA-1 antibodies also appeared to protect the Tanzanian study participants from severe cases of malaria. The investigators measured antibodies to PfSEA-1 in the entire cohort of 785 children and found that, among those with antibodies to PfSEA-1, there were no cases of severe malaria.
To generalize their results, the researchers then went back to serum samples they had collected from 140 children in Kenya in 1997. Analyses revealed that individuals with antibodies to PfSEA-1 had 50% lower parasitemia than individuals without these antibodies during a high-transmission season.
The investigators believe these findings could bring researchers a step closer to an effective malaria vaccine that targets parasites at multiple life stages.
“We still have additional trials ahead of us, first in another animal model, but we hope to begin phase 1 trials in humans very soon,” Dr Kurtis said.
“Our findings support PfSEA-1 as a potential vaccine candidate. And we are confident that, by partnering with our colleagues at the National Institutes of Health and other researchers focused on vaccines to prevent the parasites from entering red blood cells, we can approach the parasite from all angles, which could help us develop a truly effective vaccine to prevent this infectious disease that kills millions of children every year.”