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Malaria vaccine not “just around the corner”
Newsdesk Bacteriophages—the new antibiotics in-vitro study showed bacterial numbers were reduced by several orders of magnitude. Although lytic phages have been used previously to
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
Science Photo Library
A genetically engineered bacteriophage has been effectively used to deliver antibacterial agents to Escherichia coli (Antimicrob Agents Chemotherapy 2003; 47: 1301–07). A group at the Medical University of South Carolina, Charleston, SC, USA injected E coli into the abdominal cavity of mice, followed by an M13 phagemid delivery system carrying genes for the Gef and chpBK proteins. According to Caroline Westwater, these toxins are encoded in the E coli genome and although their function is unknown it has been postulated that they may serve as a mechanism for altruistic cell death during nutritional stress. They were selected because “we and others had previously shown that these toxins exerted a bactericidal effect in E coli”, says Westwater. The bacteriophages had a dramatic effect on infection, resulting in a 98% reduction in bacterial titre. A parallel
Bacteriophage attacking Escherichia coli
treat bacterial infections, Westwater believes that theirs is the first group to try to create a genetically engineered targeted delivery vehicle capable of injecting lethal gene products. Donna Duckworth, University of
Florida, Gainesville, USA, shares the view that phage can have a dramatic effect on the numbers of bacteria in an animal. “They can be used either in their natural state, as we and others have done with animal models, or they can be engineered to deliver lethal products, as the Charleston group has done. But there is no doubt that phage can be very effective as antibiotics, as years of work with humans in eastern Europe has shown.” The emergence and increasing prevalence of multidrug-resistant bacteria highlights the need for new and innovative approaches to antimicrobial treatment. Duckworth thinks that “phage will certainly be one of a number of alternate therapies for drug-resistant bacteria”, and Westwater sees lethal agent delivery systems being developed for a multitude of bacterial pathogens. Cathel Kerr
Malaria vaccine not “just around the corner” The International Society of Travel Medicine was warned that a licensed, effective malaria vaccine is still a long way off. Speaking at the society’s eighth conference (May 7–11; New York), Daniel J Carucci, a key researcher in the Plasmodium falciparum genome sequencing project and director of the malaria programme at the US Naval Medical Research Center, Silver Spring, MA, USA, cautioned that: “It is such a complex parasite, with two hosts and more than 5300 genes with stagespecific expression of proteins, that it has coevolved with human beings and developed mechanisms to avoid and modulate the host immune system”. There is evidence that a malaria vaccine is an achievable goal as indicated by the naturally acquired immunity seen in African children, who, if they survive up to age 10 are unlikely to have severe disease. Furthermore, studies using irradiated sporozoites (the parasite stage that is transmitted from mosquitoes to people) have shown a 95% protection lasting for at least 9 months. The recent
394
sequencing of the genomes of human and rodent malaria parasites P falciparum and Plasmodium yoelii has been hailed a powerful tool that will revolutionise and accelerate drug and vaccine design. Carucci said that although genomics and proteomics provide vast numbers of candidate antigens, “the key antigens may not yet be identified”. Vaccine developers need to identify targets of protective immunity and develop vaccine delivery systems capable of generating desired immune response. The target could either be a small subset of one to five proteins, up to 15 well-characterised proteins, or even the complete or large subset of the complete genome, which should produce whole-organism immunity. There are several types of candidate vaccine. Transmission-blocking vaccines that block parasite development in the mosquito include Plasmodium vivax vaccine PVS25, which is in phase 1 testing, and a P falciparum PFS25 is in development; field assessment of these candidates will be challenging. There are three blood-stage vaccines being
assessed and five pre-erythrocytic-stage vaccines including the RTS S vaccine which, according to Carucci, provided “30–80% short-term protection from challenge and 70% short-term protection in immune adults in Gambia”. Other multistage vaccines target several stages of parasite development simultaneously and six such candidate vaccines are in the testing pipeline. An effective malaria vaccine will ultimately be needed to target multiple antigens and multiple stages simultaneously and should generate both antibody and Tcell response as well as immunological memory. Carucci sees current research as promising: “more malaria vaccines are in clinical development than ever. Genomics and proteomics offer insights into the identification of protective antigens”. For 50 years we have been promised that the malaria vaccine is “just around the corner”. Not so, said Carucci “this is an enormously complex vaccine challenge that will need years to tackle”. Patricia Schlagenhauf
THE LANCET Infectious Diseases Vol 3 July 2003
For personal use. Only reproduce with permission from The Lancet.
http://infection.thelancet.com
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
Science Photo Library
A genetically engineered bacteriophage has been effectively used to deliver antibacterial agents to Escherichia coli (Antimicrob Agents Chemotherapy 2003; 47: 1301–07). A group at the Medical University of South Carolina, Charleston, SC, USA injected E coli into the abdominal cavity of mice, followed by an M13 phagemid delivery system carrying genes for the Gef and chpBK proteins. According to Caroline Westwater, these toxins are encoded in the E coli genome and although their function is unknown it has been postulated that they may serve as a mechanism for altruistic cell death during nutritional stress. They were selected because “we and others had previously shown that these toxins exerted a bactericidal effect in E coli”, says Westwater. The bacteriophages had a dramatic effect on infection, resulting in a 98% reduction in bacterial titre. A parallel
Bacteriophage attacking Escherichia coli
treat bacterial infections, Westwater believes that theirs is the first group to try to create a genetically engineered targeted delivery vehicle capable of injecting lethal gene products. Donna Duckworth, University of
Florida, Gainesville, USA, shares the view that phage can have a dramatic effect on the numbers of bacteria in an animal. “They can be used either in their natural state, as we and others have done with animal models, or they can be engineered to deliver lethal products, as the Charleston group has done. But there is no doubt that phage can be very effective as antibiotics, as years of work with humans in eastern Europe has shown.” The emergence and increasing prevalence of multidrug-resistant bacteria highlights the need for new and innovative approaches to antimicrobial treatment. Duckworth thinks that “phage will certainly be one of a number of alternate therapies for drug-resistant bacteria”, and Westwater sees lethal agent delivery systems being developed for a multitude of bacterial pathogens. Cathel Kerr
Malaria vaccine not “just around the corner” The International Society of Travel Medicine was warned that a licensed, effective malaria vaccine is still a long way off. Speaking at the society’s eighth conference (May 7–11; New York), Daniel J Carucci, a key researcher in the Plasmodium falciparum genome sequencing project and director of the malaria programme at the US Naval Medical Research Center, Silver Spring, MA, USA, cautioned that: “It is such a complex parasite, with two hosts and more than 5300 genes with stagespecific expression of proteins, that it has coevolved with human beings and developed mechanisms to avoid and modulate the host immune system”. There is evidence that a malaria vaccine is an achievable goal as indicated by the naturally acquired immunity seen in African children, who, if they survive up to age 10 are unlikely to have severe disease. Furthermore, studies using irradiated sporozoites (the parasite stage that is transmitted from mosquitoes to people) have shown a 95% protection lasting for at least 9 months. The recent
394
sequencing of the genomes of human and rodent malaria parasites P falciparum and Plasmodium yoelii has been hailed a powerful tool that will revolutionise and accelerate drug and vaccine design. Carucci said that although genomics and proteomics provide vast numbers of candidate antigens, “the key antigens may not yet be identified”. Vaccine developers need to identify targets of protective immunity and develop vaccine delivery systems capable of generating desired immune response. The target could either be a small subset of one to five proteins, up to 15 well-characterised proteins, or even the complete or large subset of the complete genome, which should produce whole-organism immunity. There are several types of candidate vaccine. Transmission-blocking vaccines that block parasite development in the mosquito include Plasmodium vivax vaccine PVS25, which is in phase 1 testing, and a P falciparum PFS25 is in development; field assessment of these candidates will be challenging. There are three blood-stage vaccines being
assessed and five pre-erythrocytic-stage vaccines including the RTS S vaccine which, according to Carucci, provided “30–80% short-term protection from challenge and 70% short-term protection in immune adults in Gambia”. Other multistage vaccines target several stages of parasite development simultaneously and six such candidate vaccines are in the testing pipeline. An effective malaria vaccine will ultimately be needed to target multiple antigens and multiple stages simultaneously and should generate both antibody and Tcell response as well as immunological memory. Carucci sees current research as promising: “more malaria vaccines are in clinical development than ever. Genomics and proteomics offer insights into the identification of protective antigens”. For 50 years we have been promised that the malaria vaccine is “just around the corner”. Not so, said Carucci “this is an enormously complex vaccine challenge that will need years to tackle”. Patricia Schlagenhauf
THE LANCET Infectious Diseases Vol 3 July 2003
For personal use. Only reproduce with permission from The Lancet.
http://infection.thelancet.com