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New treatment for chronic disease from government of Singapore
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New treatment for chronic disease from government of Singapore

PATIENT, HEAL THYSELF: SOLUTION TO PERSONALISED TREATMENT FOR CHRONIC INFECTIONS COULD LIE IN THE PATIENT’S OWN BLOOD

This discovery gives hope for a more effective and cheaper treatment strategy to millions worldwide suffering from chronic infections

1. A recent discovery by scientists at A*STAR's Singapore Institute for Clinical Sciences (SICS), in close collaboration with researchers at the Singapore Immunology Network (SIgN), provides hope for a new personalised treatment strategy that could use a patient's own blood to treat the infection. This could help treat millions of people living with chronic infections such as HIV, Hepatitis B or Hepatitis C. These findings were published in the August 2013 issue of The Journal of Clinical Investigation.

2. Patients suffering from chronic infections often have to undergo long periods of anti-viral drug therapy to control the virus. Anti-viral drugs are not fully effective against viruses such as Hepatitis B and Hepatitis C, which have chronically-infected about 400 million worldwide with more than 1,000,000 people dying from Hepatitis-related diseases every year. [1]

3. Vaccines are a potentially effective means to treat chronic viral infections such as this because they can eliminate the virus naturally. However, vaccines for patients with chronic infections are often difficult to produce since these patients already have weak immune responses or the vaccine is not effective due to genetic diversity amongst viruses.

4. The team at SICS led by Prof Antonio Bertoletti has discovered that monocytes, a type of white blood cell that can activate an immune response, are able to capture the virus in chronically-infected patients and use the captured virus to boost the patient's own immune response.

5. By using the viral antigen already present in the blood of the patient suffering from a chronic illness, this strategy redefines therapeutic vaccines by cutting down on time and resources as there is no need to specially isolate the viral proteins from patients, purify it, and then inactivate it to create a vaccine.

6. All the proteins present within the virus can be used to create a personalised vaccine for each individual. This also means that many of the complex issues associated with current vaccine therapy against chronic infections can be overcome, such as that of genetic diversity of viruses.

7. One of the greatest beneficiaries of this discovery would be chronically-infected patient populations in lower socio-economic strata. By tailoring vaccines to be more specific to each virus and each patient, vaccine production can be simplified and thus less costly. Vaccines produced via this discovery could improve the accessibility of such treatments.

8. Prof Bertoletti said, "Mobilizing the immune system to use the virus within the patient for a vaccine is a simple idea that could lead to a personalised, yet widely applicable, vaccine for chronic infections."

9. Prof Judith Swain, Executive Director of SICS said, "This excellent collaborative discovery between SICS and SIgN is a milestone in vaccine therapy for chronic infections. I believe that these findings will go a long way in improving future therapeutic treatments for chronic infections."

______________________________________________________________________

Notes for Editor: The research findings described in this media release can be found in the August 2013 online issue of The Journal of Clinical Investigation under the title, "Mobilizing monocytes to cross-present circulating viral antigen in chronic infection" by Adam J. Gehring1, Muzlifah Haniffa2,3, Patrick Kennedy4, Zi Zong Ho1, Carolina Boni5, Amanda Shin3, Nasirah Banu1, Adeline Chia1, Seng Gee Lim6, Carlo Ferrari5, Florent Ginhoux3, and Antonio Bertoletti1,7,8 1 Infection and Immunity Programme, Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. 2 Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom. 3 Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Singapore. 4 Center for Digestive Disease, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, United Kingdom. 5 Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. 6 Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 7 Program Emerging Viral Diseases, Duke-NUS Graduate Medical School, Singapore. 8 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ________________________________________________________________

AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (A*STAR) For media queries and clarifications, please contact: Vithya Selvam (Ms) Corporate Communications Agency for Science, Technology and Research Tel: (+65) 6826 6291 Email: vithya_selvam***@****sg________________________________________________________________

About the Agency for Science, Technology and Research (A*STAR) The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity. A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, and with other local and international partners. For more information about A*STAR, please visit www.a-star.edu.sg.
About the Singapore Institute for Clinical Sciences (SICS) Established in 2007, the Singapore Institute for Clinical Sciences (SICS) is a research institute within the Agency for Science, Technology and Research (A*STAR), and its mission is to develop disease-oriented clinical and translational research programmes in key disease areas.
SICS is distinguished by its focus on clinical sciences and the use of innovative approaches and technologies that enable the efficient and effective study of human health and diseases. The clinical scientists in SICS conduct the full spectrum of "bench to bedside" research activities in metabolic diseases (including diabetes, obesity and insulin resistance), pathways to normal growth and development (including cognitive and behavioural development), nutritional sciences as well as in certain viral infectious diseases such as chronic viral diseases.
The institute aims to attract, train and nurture clinician-scientists and to develop joint programs with universities, academic medical centres, government hospitals and research institutes. For more information on SICS, please visit: www.sics.a-star.edu.sg.
5 Comments Post a Comment
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Avatar_m_tn
I think the media release oversimplified the research findings. Of course, the research is almost impossible to understand for layman like myself, but it should be a delight for studyforhope. I don't think the research has shown a way to actually develop a therapeutic vaccine, but has indicated that it may be possible.

Just my very amateur opinion.
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Avatar_m_tn
Here is the abstract of the paper that caused all this fancy press talk about a vaccine out of a patients blood


Mobilizing monocytes to cross-present circulating viral antigen in chronic infection.
Gehring AJ, Haniffa M, Kennedy PT, Ho ZZ, Boni C, Shin A, Banu N, Chia A, Lim SG, Ferrari C, Ginhoux F, Bertoletti A.
Abstract
Selection of antigens for therapeutic vaccination against chronic viral infections is complicated by pathogen genetic variations. We tested whether antigens present during persistent viral infections could provide a personalized antigenic reservoir for therapeutic T cell expansion in humans. We focused our study on the HBV surface antigen (HBsAg), which is present in microgram quantities in the serum of chronic HBV patients. We demonstrated by quantitative fluorescent microscopy that, out of 6 professional APC populations in the circulation, only CD14 monocytes (MNs) retained an HBsAg depot. Using TCR-redirected CD8+ T cells specific for MHC-I-restricted HBV epitopes, we showed that, despite being constantly exposed to antigen, ex vivo-isolated APCs did not constitutively activate HBV-specific CD8+ T cells. However, differentiation of HBsAg+ CD14 MNs from chronic patients to MN-derived DCs (moDCs) induced cross-presentation of the intracellular reservoir of viral antigen. We exploited this mechanism to cross-present circulating viral antigen and showed that moDCs from chronically infected patients stimulated expansion of autologous HBV-specific T cells. Thus, these data demonstrate that circulating viral antigen produced during chronic infection can serve as a personalized antigenic reservoir to activate virus-specific T cells.
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Avatar_m_tn
Yes, exactly. The method that was portrayed by media being oversimplified so that we may not clearly understand the underlying mechanism of this therapeutic vaccine.

I think this is an attempt to eradicate HBV which was declared by both Taiwanese and Singaporean researchers that they will win HBV war by 2015.



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Avatar_m_tn
And here is in a nutshell what the real story is about.


Monocytes often also called Macrophages, pick up debris floating in plasma and interstitial fluids. Thus they pick up the huge amount of surface antigen particles present in HBV plasma. They partially digest it and also store it for a while.

As antigen presenting cells they are not very good, however. Thus they fail to activate surface antigen specific epitope recognizing cd8 and cd4 cells.

Monocytes can be tricked in vitro, called here ex vivo, to differentiate into dendritic cells, which specialize to present to and  activate T cells.

So bertolettis group was able to stimulate monocytes from HBV patients to become dendritic cells and then those cells started to activate T cells , in vitro.

This is nice, but a rather large amount of blood would need to be stimulated to induce the differentiation from monos to dendritic cells and the those cells would need to be reintroduced into the patient.

You cannot stimulate that transition from monocytes to dendritic cells inside a patient. Technically close to impossible and certainly extremely dangerous.

Thus in summary an interesting idea and good research with theoretical clinical usefulness.
But far from cheap to do and the press talk about a possible solution for poor countries is, well, just press talk.
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Avatar_m_tn
Thank you Studyforhope for your clarification.
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