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Edible vaccine for hepatitis B
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boosting with adenoviral vectors encoding viral proteins. Four macaques immunised in this way survived infection with the most virulent strain and mounted both a humoral and cellular immune response resulting in virus clearance in 2 weeks. The vaccinated animals remained healthy for up to 6 months following infection whereas control animals died within 1 week. The monkeys were infected with a relatively small amount of virus and it remains to be seen whether the vaccine is effective against a more substantial challenge and, more importantly, whether it can protect humans. HM 1 Sullivan, N.J. et al. (2000) Development of a preventative vaccine for Ebola virus infection in primates. Nature 408, 605–609
Diabetes protection Scientists from Bristol University, headed by Dr Neil Williams, have found that NOD mice immunised with a non-toxic form of an Escherichia coli enterotoxin do not develop diabetes. Dr Williams, Senior Lecturer in Immunology at Bristol University (http://www.pam.bris.ac.uk/) presented the team’s findings in December at the British Society for Immunology Congress in Harrogate. NOD mice normally develop pancreatic inflammation (peri-insulitis) at around 6–8 weeks and the consequent diabetes from 14 weeks of age onwards. The research team found that the bacterial protein EtxB, but not the receptor nonbinding protein EtxB (G33D), can prevent diabetes developing. The protein was administered intranasally at 10–12 weeks of age (once the mice have developed periinsulitis). Further studies showed that T cells isolated from the spleens of treated mice can also confer protection if injected into naive recipients. A new pharmaceutical company, Aegis Pharmaceuticals Ltd, is developing the drug for human trials. Dr Williams cautioned, ‘The process of getting the treatment from the laboratory into patients takes some time, however, we are hopeful that we will be able to test it in controlled trials within the next two years.’ HM
MHC on the brain A report in the 15th December issue of Science shows that class I MHC and CD3-ζ are found in the brains of mice. A group from Harvard Medical School led by Carla Shatz, Professor of Neurobiology, demonstrated that the two immune proteins were necessary for accurate assembly of the brain. Both
TRENDS in Immunology Vol.22 No.2 February 2001
proteins were found in the hippocampus, the region of the brain associated with learning, and the lateral geniculate nucleus, the visual area of the brain. Neural connections between the retina and the geniculate nucleus were abnormal in mice genetically deficient for class I MHC or CD3- ζ. Furthermore, mutant mice also experienced impaired functioning in the hippocampus. In normal mice, high levels of class I MHC are found in primary sensory areas of the brain, which are thought to function abnormally in dyslexia. Future studies hope to show whether mutant mice have problems processing sensory information. Although a link with dyslexia is still speculative, preliminary studies by other researchers have shown that some families with dyslexia carry genetic defects on chromosome 6, the same chromosome that carries the class I MHC genes. This finding has important implications for other neurodegenerative conditions such as Parkinson’s and multiple sclerosis, which could be the result of an autoimmune attack on class I MHC-bearing neurons. HM 1 Huh, G.S. et al. (2000) Functional requirement of class I MHC in CNS development and plasticity. Science 290, 2155–2159
Edible vaccine for hepatitis B Edible vaccines could play a major role in future protection against hepatitis B infection, according to Professor Yasmin Thanavala from Roswell Park Cancer Institute, USA. Speaking at the British Society of Immunology Meeting in Harrogate, she explained how edible plants carrying a hepatitis B surface antigen (HbsAg) transgene could provide a new means of immunising against hepatitis B. She stated, ‘the advantages of such an approach could be enormous. This technology would allow for indigenous production of vaccines wherever possible, allowing in-country vaccine production as a national sustainable priority’. This work, which has been published in Nature Biotechnology, shows that mice fed transgenic HbsAg potato tubers mounted a primary antibody response, which could be boosted by intraperitoneal delivery of a single subimmunogenic dose of commercial HbsAg vaccine. Such a vaccine would not require syringes and needles, reducing costs and, most importantly, preventing spread of infection owing to reuse and misuse of needles. Professor Thanavala stresses that ‘it is important to distinguish that this is a
71
vaccine and not food that will be available in grocery stores.’ HM 1 Richter, L.J. et al. (2000) Production of hepatitis B surface antigen in transgenic plants for oral immunisation. Nat. Biotechnol. 18, 1167–1171
Ineffective treatment for asthma Two studies reported in the December 23rd issue of the Lancet look at the effects of administering anti-IL5 or IL-12 on eosinophils, airway hyper-responsiveness and the late asthmatic response. Airway eosinophilia, commonly found in asthmatic patients, is associated with a predominance of Th2 cells, which produce IL-4, -5, -9 and -13. Margaret Leckie, from the National Heart and Lung Institute (NHIL), Imperial College, London, and a team of collaborators examined the efficacy of a monoclonal antibody to IL-5 in allergic asthmatic volunteers. A single injection of the antibody was well tolerated and caused a dramatic reduction in eosinophil counts in blood and sputum. However, unlike previous animal studies, the drop in eosinophil counts was not accompanied by changes in the early or late response to allergen challenge or in airway hyper-responsiveness to histamine. In a second paper, Shannon Bryan (NHIL) and colleagues tried to shift the CD4+T cell response from Th2 to Th1 by administering IL-12. Most patients suffered ‘flu-like symptoms and three had serious hepatic or cardiac side effects. A similar reduction in eosinophils was found, again with no concomitant reduction in the late asthmatic response or allergen-induced increases in bronchial reactivity to histamine. The authors concede that anti-IL-5 treatment and other anti-eosinophil treatments might have limited use in asthma treatment but could be of use in diseases associated with eosinophilia. HM 1 Leckie, M.J. et al. (2000) Effects of an interleukin5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness and the late asthmatic response. Lancet 356, 9248 2 Bryan, S.A. et al. (2000) Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356, 9248
This month’s In Brief articles were compiled by Hilary Marshall ([email protected])
http://immunology.trends.com 1471-4906/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
boosting with adenoviral vectors encoding viral proteins. Four macaques immunised in this way survived infection with the most virulent strain and mounted both a humoral and cellular immune response resulting in virus clearance in 2 weeks. The vaccinated animals remained healthy for up to 6 months following infection whereas control animals died within 1 week. The monkeys were infected with a relatively small amount of virus and it remains to be seen whether the vaccine is effective against a more substantial challenge and, more importantly, whether it can protect humans. HM 1 Sullivan, N.J. et al. (2000) Development of a preventative vaccine for Ebola virus infection in primates. Nature 408, 605–609
Diabetes protection Scientists from Bristol University, headed by Dr Neil Williams, have found that NOD mice immunised with a non-toxic form of an Escherichia coli enterotoxin do not develop diabetes. Dr Williams, Senior Lecturer in Immunology at Bristol University (http://www.pam.bris.ac.uk/) presented the team’s findings in December at the British Society for Immunology Congress in Harrogate. NOD mice normally develop pancreatic inflammation (peri-insulitis) at around 6–8 weeks and the consequent diabetes from 14 weeks of age onwards. The research team found that the bacterial protein EtxB, but not the receptor nonbinding protein EtxB (G33D), can prevent diabetes developing. The protein was administered intranasally at 10–12 weeks of age (once the mice have developed periinsulitis). Further studies showed that T cells isolated from the spleens of treated mice can also confer protection if injected into naive recipients. A new pharmaceutical company, Aegis Pharmaceuticals Ltd, is developing the drug for human trials. Dr Williams cautioned, ‘The process of getting the treatment from the laboratory into patients takes some time, however, we are hopeful that we will be able to test it in controlled trials within the next two years.’ HM
MHC on the brain A report in the 15th December issue of Science shows that class I MHC and CD3-ζ are found in the brains of mice. A group from Harvard Medical School led by Carla Shatz, Professor of Neurobiology, demonstrated that the two immune proteins were necessary for accurate assembly of the brain. Both
TRENDS in Immunology Vol.22 No.2 February 2001
proteins were found in the hippocampus, the region of the brain associated with learning, and the lateral geniculate nucleus, the visual area of the brain. Neural connections between the retina and the geniculate nucleus were abnormal in mice genetically deficient for class I MHC or CD3- ζ. Furthermore, mutant mice also experienced impaired functioning in the hippocampus. In normal mice, high levels of class I MHC are found in primary sensory areas of the brain, which are thought to function abnormally in dyslexia. Future studies hope to show whether mutant mice have problems processing sensory information. Although a link with dyslexia is still speculative, preliminary studies by other researchers have shown that some families with dyslexia carry genetic defects on chromosome 6, the same chromosome that carries the class I MHC genes. This finding has important implications for other neurodegenerative conditions such as Parkinson’s and multiple sclerosis, which could be the result of an autoimmune attack on class I MHC-bearing neurons. HM 1 Huh, G.S. et al. (2000) Functional requirement of class I MHC in CNS development and plasticity. Science 290, 2155–2159
Edible vaccine for hepatitis B Edible vaccines could play a major role in future protection against hepatitis B infection, according to Professor Yasmin Thanavala from Roswell Park Cancer Institute, USA. Speaking at the British Society of Immunology Meeting in Harrogate, she explained how edible plants carrying a hepatitis B surface antigen (HbsAg) transgene could provide a new means of immunising against hepatitis B. She stated, ‘the advantages of such an approach could be enormous. This technology would allow for indigenous production of vaccines wherever possible, allowing in-country vaccine production as a national sustainable priority’. This work, which has been published in Nature Biotechnology, shows that mice fed transgenic HbsAg potato tubers mounted a primary antibody response, which could be boosted by intraperitoneal delivery of a single subimmunogenic dose of commercial HbsAg vaccine. Such a vaccine would not require syringes and needles, reducing costs and, most importantly, preventing spread of infection owing to reuse and misuse of needles. Professor Thanavala stresses that ‘it is important to distinguish that this is a
71
vaccine and not food that will be available in grocery stores.’ HM 1 Richter, L.J. et al. (2000) Production of hepatitis B surface antigen in transgenic plants for oral immunisation. Nat. Biotechnol. 18, 1167–1171
Ineffective treatment for asthma Two studies reported in the December 23rd issue of the Lancet look at the effects of administering anti-IL5 or IL-12 on eosinophils, airway hyper-responsiveness and the late asthmatic response. Airway eosinophilia, commonly found in asthmatic patients, is associated with a predominance of Th2 cells, which produce IL-4, -5, -9 and -13. Margaret Leckie, from the National Heart and Lung Institute (NHIL), Imperial College, London, and a team of collaborators examined the efficacy of a monoclonal antibody to IL-5 in allergic asthmatic volunteers. A single injection of the antibody was well tolerated and caused a dramatic reduction in eosinophil counts in blood and sputum. However, unlike previous animal studies, the drop in eosinophil counts was not accompanied by changes in the early or late response to allergen challenge or in airway hyper-responsiveness to histamine. In a second paper, Shannon Bryan (NHIL) and colleagues tried to shift the CD4+T cell response from Th2 to Th1 by administering IL-12. Most patients suffered ‘flu-like symptoms and three had serious hepatic or cardiac side effects. A similar reduction in eosinophils was found, again with no concomitant reduction in the late asthmatic response or allergen-induced increases in bronchial reactivity to histamine. The authors concede that anti-IL-5 treatment and other anti-eosinophil treatments might have limited use in asthma treatment but could be of use in diseases associated with eosinophilia. HM 1 Leckie, M.J. et al. (2000) Effects of an interleukin5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness and the late asthmatic response. Lancet 356, 9248 2 Bryan, S.A. et al. (2000) Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356, 9248
This month’s In Brief articles were compiled by Hilary Marshall ([email protected])
http://immunology.trends.com 1471-4906/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.