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a red blood cell; Credit: St Jude
Children’s Research Hospital
Scientists have reported that injecting cryopreserved malaria sporozoites in human subjects can result in controlled infection.
This indicates that direct injection of sporozoites can be used in lieu of mosquito bites to test the efficacy of malaria drugs or vaccines in human volunteers.
The findings from this study were reported at the annual meeting of the American Society of Tropical Medicine and Hygiene and published online in the American Journal of Tropical Medicine and Hygiene.
“Our study shows it’s possible to manufacture and then administer controlled doses of malaria parasites using a needle and syringe to deliver a formulation that can meet regulatory standards for purity and dose consistency,” said study author Meta Roestenberg, MD, of the Radboud University Nijmegen Medical Center in The Netherlands.
She and her colleagues noted that the current method of testing malaria drugs and vaccines by exposing subjects to mosquito bites is technically complex and costly. And there are only a few places in the world today where such work is being done.
In addition, when using mosquitoes to deliver malaria parasites, it can be difficult to ensure that all subjects receive the same level of infection. And that can influence the outcome of the treatment.
So Dr Roestenberg and her colleagues set out to find a better way. They tested cryopreserved Plasmodium falciparum sporozoites that were harvested from the salivary glands of infected mosquitoes and had been frozen for more than 2 years. The sporozoites were manufactured by the Maryland-based biotechnology company Sanaria Inc.
The researchers enrolled 18 healthy volunteers and divided them into 3 groups. The first group received 2500 sporozoites, the second received 10,000 sporozoites, and the third received 25,000 sporozoites.
The team found that 84% of participants—5 of the 6 volunteers in each group—were safely and successfully infected with malaria. And there were no differences among the groups in the time it took for the infection to develop or the presentation of symptoms. The volunteers who developed infections subsequently received treatment and quickly recovered without incident.
“We have demonstrated the potential to develop what you might call ‘the human challenge trial in a bottle’ that could be available to scientists anywhere who need to know how a new drug or vaccine would fare against a real but carefully controlled and calibrated malaria infection,” said study author Stephen L. Hoffman, MD, of Sanaria Inc.
The researchers also said these results could aid the development of whole parasite vaccines.
“A major challenge to realizing the potential of whole parasite vaccines is the development of a stable, consistent formulation of sporozoites that can be manufactured, preserved, and used like any other vaccine,” said study author Robert W. Sauerwein, MD, PhD, also of Radboud University Nijmegen Medical Center.
Sanaria is currently pursuing clinical trials to test 2 different approaches to whole parasite vaccination: irradiated sporozoites and inducing controlled infections in tandem with the administration of antimalarial drugs.
Researchers are also planning additional trials to ensure the infection produced with the cryopreserved sporozoites mirrors what one would experience through bites from infected mosquitoes. 
a red blood cell; Credit: St Jude
Children’s Research Hospital
Scientists have reported that injecting cryopreserved malaria sporozoites in human subjects can result in controlled infection.
This indicates that direct injection of sporozoites can be used in lieu of mosquito bites to test the efficacy of malaria drugs or vaccines in human volunteers.
The findings from this study were reported at the annual meeting of the American Society of Tropical Medicine and Hygiene and published online in the American Journal of Tropical Medicine and Hygiene.
“Our study shows it’s possible to manufacture and then administer controlled doses of malaria parasites using a needle and syringe to deliver a formulation that can meet regulatory standards for purity and dose consistency,” said study author Meta Roestenberg, MD, of the Radboud University Nijmegen Medical Center in The Netherlands.
She and her colleagues noted that the current method of testing malaria drugs and vaccines by exposing subjects to mosquito bites is technically complex and costly. And there are only a few places in the world today where such work is being done.
In addition, when using mosquitoes to deliver malaria parasites, it can be difficult to ensure that all subjects receive the same level of infection. And that can influence the outcome of the treatment.
So Dr Roestenberg and her colleagues set out to find a better way. They tested cryopreserved Plasmodium falciparum sporozoites that were harvested from the salivary glands of infected mosquitoes and had been frozen for more than 2 years. The sporozoites were manufactured by the Maryland-based biotechnology company Sanaria Inc.
The researchers enrolled 18 healthy volunteers and divided them into 3 groups. The first group received 2500 sporozoites, the second received 10,000 sporozoites, and the third received 25,000 sporozoites.
The team found that 84% of participants—5 of the 6 volunteers in each group—were safely and successfully infected with malaria. And there were no differences among the groups in the time it took for the infection to develop or the presentation of symptoms. The volunteers who developed infections subsequently received treatment and quickly recovered without incident.
“We have demonstrated the potential to develop what you might call ‘the human challenge trial in a bottle’ that could be available to scientists anywhere who need to know how a new drug or vaccine would fare against a real but carefully controlled and calibrated malaria infection,” said study author Stephen L. Hoffman, MD, of Sanaria Inc.
The researchers also said these results could aid the development of whole parasite vaccines.
“A major challenge to realizing the potential of whole parasite vaccines is the development of a stable, consistent formulation of sporozoites that can be manufactured, preserved, and used like any other vaccine,” said study author Robert W. Sauerwein, MD, PhD, also of Radboud University Nijmegen Medical Center.
Sanaria is currently pursuing clinical trials to test 2 different approaches to whole parasite vaccination: irradiated sporozoites and inducing controlled infections in tandem with the administration of antimalarial drugs.
Researchers are also planning additional trials to ensure the infection produced with the cryopreserved sporozoites mirrors what one would experience through bites from infected mosquitoes.
a red blood cell; Credit: St Jude
Children’s Research Hospital
Scientists have reported that injecting cryopreserved malaria sporozoites in human subjects can result in controlled infection.
This indicates that direct injection of sporozoites can be used in lieu of mosquito bites to test the efficacy of malaria drugs or vaccines in human volunteers.
The findings from this study were reported at the annual meeting of the American Society of Tropical Medicine and Hygiene and published online in the American Journal of Tropical Medicine and Hygiene.
“Our study shows it’s possible to manufacture and then administer controlled doses of malaria parasites using a needle and syringe to deliver a formulation that can meet regulatory standards for purity and dose consistency,” said study author Meta Roestenberg, MD, of the Radboud University Nijmegen Medical Center in The Netherlands.
She and her colleagues noted that the current method of testing malaria drugs and vaccines by exposing subjects to mosquito bites is technically complex and costly. And there are only a few places in the world today where such work is being done.
In addition, when using mosquitoes to deliver malaria parasites, it can be difficult to ensure that all subjects receive the same level of infection. And that can influence the outcome of the treatment.
So Dr Roestenberg and her colleagues set out to find a better way. They tested cryopreserved Plasmodium falciparum sporozoites that were harvested from the salivary glands of infected mosquitoes and had been frozen for more than 2 years. The sporozoites were manufactured by the Maryland-based biotechnology company Sanaria Inc.
The researchers enrolled 18 healthy volunteers and divided them into 3 groups. The first group received 2500 sporozoites, the second received 10,000 sporozoites, and the third received 25,000 sporozoites.
The team found that 84% of participants—5 of the 6 volunteers in each group—were safely and successfully infected with malaria. And there were no differences among the groups in the time it took for the infection to develop or the presentation of symptoms. The volunteers who developed infections subsequently received treatment and quickly recovered without incident.
“We have demonstrated the potential to develop what you might call ‘the human challenge trial in a bottle’ that could be available to scientists anywhere who need to know how a new drug or vaccine would fare against a real but carefully controlled and calibrated malaria infection,” said study author Stephen L. Hoffman, MD, of Sanaria Inc.
The researchers also said these results could aid the development of whole parasite vaccines.
“A major challenge to realizing the potential of whole parasite vaccines is the development of a stable, consistent formulation of sporozoites that can be manufactured, preserved, and used like any other vaccine,” said study author Robert W. Sauerwein, MD, PhD, also of Radboud University Nijmegen Medical Center.
Sanaria is currently pursuing clinical trials to test 2 different approaches to whole parasite vaccination: irradiated sporozoites and inducing controlled infections in tandem with the administration of antimalarial drugs.
Researchers are also planning additional trials to ensure the infection produced with the cryopreserved sporozoites mirrors what one would experience through bites from infected mosquitoes.