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Starvation diet for Toxoplasma
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individual animals. Dohoo used a productivity trial to further evaluate the practical use of ELISA. He compared milk production after eprinomectin treatment of cows that had a high response to the test with milk production obtained from cows with a low response. The first group showed a productivity gain of ~2.9 kg milk per cow per day during the first six months of production. Dohoo suggested that ELISA could help producers and veterinarians to screen herds periodically and to decide the need and timing for parasite treatment. MH
New malaria vaccine provides 100% protection Complete protection against symptomatic malaria and total inhibition of liver- and blood-stage parasites has been observed following the use of a new malaria vaccine in mice [(2001) Proc. Natl. Acad. Sci. U. S. A. 98, 11491–11496]. Nussenzweig and her research team at the New York University School of Medicine applied their new vaccine as a prime-boost strategy. Mice were inoculated with a replication-defective recombinant adenovirus expressing the circumsporozoite protein (CS) of Plasmodium yoelii (AdPyCS) followed by a booster with an attenuated recombinant vaccinia virus also expressing CS (VacPyCS). When the two vaccines were administered separately by eight or more weeks, the researchers noted high levels of activated CS-specific CD8 + and CD4+ T cells, elevated anti-sporozoite antibody titers, and complete and long-lasting protection against disease. This indicates that immunization with AdPyCS generates highly effective memory T and B cells, which can be recalled by boosting with VacPyCS. SHK
Anthony S. Fauci awarded the 2001 Frank Annuzio award Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH), will receive the 2001 Frank Annunzio Award in the Humanitarian Field from the Christopher Columbus Fellowship Foundation. Fauci, who pioneered research into human immunoregulation, developed effective therapies for polyarteritis nodosa and Wegener’s granulomatosis. The Christopher Columbus Fellowship Foundation states that, ‘Dr Fauci has been internationally recognized as one of the http://parasites.trends.com
TRENDS in Parasitology Vol.17 No.12 December 2001
world’s leading researchers in the study of the pathogenesis and treatment of immunemediated and infectious diseases. His contributions toward understanding the regulation of the human immune response and the pathogenesis of the human immunodeficiency virus (HIV) disease are universally renowned, and have served as the basis for our current strategies for the development of effective therapies for AIDS as well as for regeneration of the damaged immune system’. For more information, see http://www.discover.com/ awards/annunzio. JVC
Starvation diet for Toxoplasma
571
IL-12: for better and for worse Interleukin 12 (IL-12) has gained more attention when it was discovered to be crucial in directing the immune response towards a type 1 response that appeared to be protective in a Leishmania–mouse model. The protective immunity against other intracellular parasites such as Toxoplasma gondii was also associated with type-1 immune responsiveness. In order to reveal the parasite antigen that could trigger IL-12 production by macrophages, it was found that live Toxoplasma or a lysate prepared from Toxoplasma tachyzoites induced secretion of the bioactive IL-12 p70 heterodimer [Schade, B. and Fischer, H-G. (2001) Vet. Parasitol. 100, 63–74]. Surprisingly, when using macrophages from different inbred mouse strains, cells from T. gondiisusceptible mice released more IL-12 following Toxoplasma challenge than those in resistant mice. Furthermore, Toxoplasma isolates that were virulent in mice became less efficient IL-12 inducers after attenuation. These results suggest that, although IL-12 induction is crucial for protective immunity to develop, overproduction of the cytokine triggers immunopathological reactions. TS
Innovative malaria vaccine to undergo clinical development
A recent study of cerebral toxoplasmosis by Däubener et al. suggests that cytokineexposed endothelial cells could limit parasite growth by starving them of amino acids essential for their survival [(2001) Infect. Immun. 69, 6527–6531]. An in vitro culture system was used to examine the interaction between human brain microvascular endothelial cells (HBMECs) and Toxoplasma gondii. After exposure to interferon γ and tumor necrosis factor α , strong induction of the tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) in the HBMECs was associated with a suppressive effect on parasite survival. This effect was completely abrogated by the addition of excess tryptophan to the cultures, highlighting this particular amino acid as crucial for parasite viability. Cerebral toxoplasmosis is a debilitating infection often seen in HIV-infected and other immunosuppressed patients. SHK
The Malaria Vaccine Initiative at the Program for Appropriate Technology in Health, USA, the University of Oxford, UK and Oxxon Pharmaccines (London, UK) recently announced an agreement to accelerate the development of an innovative malaria vaccine. The US$1.5 million, two-year programme will enable the three organisations to develop and test a vaccine based on the prime-boost technology in human volunteers. This technology, which uses a pair of modified pox viruses to expose malaria antigens to human immune cells, should increase the natural resistance of the body to malaria through a two-stage regime. Each vaccine candidate contains a gene for the same malaria antigen; one vaccine candidate will prime the immune system into producing a response, which is then boosted by the second vaccine candidate. Animal studies have already demonstrated that this primeboost technology is completely effective in providing protection from malaria. ‘This vaccine combination holds the promise of
1471-4922/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
individual animals. Dohoo used a productivity trial to further evaluate the practical use of ELISA. He compared milk production after eprinomectin treatment of cows that had a high response to the test with milk production obtained from cows with a low response. The first group showed a productivity gain of ~2.9 kg milk per cow per day during the first six months of production. Dohoo suggested that ELISA could help producers and veterinarians to screen herds periodically and to decide the need and timing for parasite treatment. MH
New malaria vaccine provides 100% protection Complete protection against symptomatic malaria and total inhibition of liver- and blood-stage parasites has been observed following the use of a new malaria vaccine in mice [(2001) Proc. Natl. Acad. Sci. U. S. A. 98, 11491–11496]. Nussenzweig and her research team at the New York University School of Medicine applied their new vaccine as a prime-boost strategy. Mice were inoculated with a replication-defective recombinant adenovirus expressing the circumsporozoite protein (CS) of Plasmodium yoelii (AdPyCS) followed by a booster with an attenuated recombinant vaccinia virus also expressing CS (VacPyCS). When the two vaccines were administered separately by eight or more weeks, the researchers noted high levels of activated CS-specific CD8 + and CD4+ T cells, elevated anti-sporozoite antibody titers, and complete and long-lasting protection against disease. This indicates that immunization with AdPyCS generates highly effective memory T and B cells, which can be recalled by boosting with VacPyCS. SHK
Anthony S. Fauci awarded the 2001 Frank Annuzio award Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH), will receive the 2001 Frank Annunzio Award in the Humanitarian Field from the Christopher Columbus Fellowship Foundation. Fauci, who pioneered research into human immunoregulation, developed effective therapies for polyarteritis nodosa and Wegener’s granulomatosis. The Christopher Columbus Fellowship Foundation states that, ‘Dr Fauci has been internationally recognized as one of the http://parasites.trends.com
TRENDS in Parasitology Vol.17 No.12 December 2001
world’s leading researchers in the study of the pathogenesis and treatment of immunemediated and infectious diseases. His contributions toward understanding the regulation of the human immune response and the pathogenesis of the human immunodeficiency virus (HIV) disease are universally renowned, and have served as the basis for our current strategies for the development of effective therapies for AIDS as well as for regeneration of the damaged immune system’. For more information, see http://www.discover.com/ awards/annunzio. JVC
Starvation diet for Toxoplasma
571
IL-12: for better and for worse Interleukin 12 (IL-12) has gained more attention when it was discovered to be crucial in directing the immune response towards a type 1 response that appeared to be protective in a Leishmania–mouse model. The protective immunity against other intracellular parasites such as Toxoplasma gondii was also associated with type-1 immune responsiveness. In order to reveal the parasite antigen that could trigger IL-12 production by macrophages, it was found that live Toxoplasma or a lysate prepared from Toxoplasma tachyzoites induced secretion of the bioactive IL-12 p70 heterodimer [Schade, B. and Fischer, H-G. (2001) Vet. Parasitol. 100, 63–74]. Surprisingly, when using macrophages from different inbred mouse strains, cells from T. gondiisusceptible mice released more IL-12 following Toxoplasma challenge than those in resistant mice. Furthermore, Toxoplasma isolates that were virulent in mice became less efficient IL-12 inducers after attenuation. These results suggest that, although IL-12 induction is crucial for protective immunity to develop, overproduction of the cytokine triggers immunopathological reactions. TS
Innovative malaria vaccine to undergo clinical development
A recent study of cerebral toxoplasmosis by Däubener et al. suggests that cytokineexposed endothelial cells could limit parasite growth by starving them of amino acids essential for their survival [(2001) Infect. Immun. 69, 6527–6531]. An in vitro culture system was used to examine the interaction between human brain microvascular endothelial cells (HBMECs) and Toxoplasma gondii. After exposure to interferon γ and tumor necrosis factor α , strong induction of the tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) in the HBMECs was associated with a suppressive effect on parasite survival. This effect was completely abrogated by the addition of excess tryptophan to the cultures, highlighting this particular amino acid as crucial for parasite viability. Cerebral toxoplasmosis is a debilitating infection often seen in HIV-infected and other immunosuppressed patients. SHK
The Malaria Vaccine Initiative at the Program for Appropriate Technology in Health, USA, the University of Oxford, UK and Oxxon Pharmaccines (London, UK) recently announced an agreement to accelerate the development of an innovative malaria vaccine. The US$1.5 million, two-year programme will enable the three organisations to develop and test a vaccine based on the prime-boost technology in human volunteers. This technology, which uses a pair of modified pox viruses to expose malaria antigens to human immune cells, should increase the natural resistance of the body to malaria through a two-stage regime. Each vaccine candidate contains a gene for the same malaria antigen; one vaccine candidate will prime the immune system into producing a response, which is then boosted by the second vaccine candidate. Animal studies have already demonstrated that this primeboost technology is completely effective in providing protection from malaria. ‘This vaccine combination holds the promise of
1471-4922/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.