Characterisation Of Anti-HBs Responses In Patients Undergoing Functional Hepatitis B Cure: Implication For Future Therapies
Funder
National Health and Medical Research Council
Funding Amount
$723,649.00
Summary
The hepatitis B virus causes liver cirrhosis and liver cancer. There is no cure for hepatitis B. However, a small number of patients can naturally rid themselves of the virus. We have identified 14 of these individuals and discovered that they have a unique immune response that is responsible for these “natural” cures. We plan to characterise this immune response and turn it into a therapeutic vaccine which can be used to cure patients who are still chronically infected.
Investigating The Host Determinants Of Viral Clearance Versus Collateral Pathology In Chronic Infection
Funder
National Health and Medical Research Council
Funding Amount
$1,250,756.00
Summary
Hepatitis B virus has infected over 2 billion people. Some people control the virus but it remains incurable and there is a lifelong risk of liver cancer. Understanding how host cells interact with the virus, the mechanisms the cells use in an attempt to eliminate the virus and the mechanisms the virus uses to sabotage these responses, will provide insights that could lead to therapies. Potential therapies could be applicable to other infections like HIV-1 and tuberculosis.
The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
The Molecular Determinants Of Immunological Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Autoimmune diseases, such as type I diabetes and multiple sclerosis, are debilitating disorders that impose a massive toll on wellbeing in Australia and worldwide. This fellowship will support research aimed at determining the genes and mechanisms that control autoimmunity. New technologies will be brought to bear to track immune cells throughout their development, maturity and malfunction in disease settings. We aim to uncover new therapeutic targets to prevent and reverse autoimmune disease.
Determinants Of Sustained Virological Response After Discontinuation Of Long-term Nucleoside Analogue Therapy In Chronic Hepatitis B Patients
Funder
National Health and Medical Research Council
Funding Amount
$976,778.00
Summary
Guidelines currently recommend lifelong treatment for patients with chronic hepatitis B, with associated cost and risks of drug resistance and side effects. It has recently been suggested that up to 50% of patients may safely and successfully stop drug after long-term treatment. Our project will identify which patients can safely stop treatment, by performing detailed studies of the human immune system and the hepatitis B virus. This will be an important advance for patient care.
How Do Cross-reactive Memory B Cells Affect Influenza Vaccine Titers?
Funder
National Health and Medical Research Council
Funding Amount
$798,049.00
Summary
Influenza vaccines are updated frequently to protect against the highly variable influenza virus. Despite careful selection of vaccine viruses, most influenza vaccines provide only modest protection and protection is poor some years. In turn, the response to vaccination varies between individuals. This probably reflects complex and variable histories of influenza infection and vaccination. The project investigates how past influenza exposure influences vaccine responses and effectiveness.
Targeting Adenosine Mediated Immunosuppression To Enhance CAR T Cell Activity
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
The use of white blood cells genetically engineered to eradicate cancer cells specifically has been a major breakthrough in cancer treatment. These cells (CAR T cells) are very effective in blood cancers, but do not currently work well in other cancers. This is due to the immune suppressing nature of the cancer environment. I propose to use strategies to overcome this by genetically reprogramming the CAR T cells to be resistant to suppression by the cancer and therefore be more effective.
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
New Drug Combinations To Enhance Elimination Of Hepatitis B Infection
Funder
National Health and Medical Research Council
Funding Amount
$888,304.00
Summary
We have developed a therapy that kills hepatitis B virus infected cells and promotes elimination of infection. We are now testing novel drugs that can be used to maximise the efficacy of our new treatment to promote better outcomes that may be translated to other infections.
Long Term Persistence Of HIV In The Liver And The Clinical Impact On HIV-HBV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$1,393,245.00
Summary
This grant will address a major question in HIV cure research - the role of the liver as an HIV reservoir and the impact of HIV persistence in HIV-infected patients on suppressive antiretroviral therapy (ART) on liver disease, in the setting of HIV-HBV co-infection. We will trial a novel intervention to reduce HIV infection of the liver that could potentially reduce chronic liver disease in this setting.