Prevention Of HIV-1 Infection By Adeno Associated Virus Vector-delivered Broadly Neutralizing Antibodies Or Antibody-like Molecules
Funder
National Health and Medical Research Council
Funding Amount
$875,854.00
Summary
A promising neutralizing molecule has boosted hopes of an HIV vaccine. It remains unknown how well this molecule prevents HIV infection under conditions reflecting “real world” exposure, including exposure to HIV in the form of cells carrying virus or free-floating virus in the presence of semen. We will assess this molecule for their ability to inhibit transmission of HIV-like viruses under these conditions. These experiments will define requirements to protect against HIV infection.
Randomised Trial To Determine The Safety And Efficacy Of Early Vs Deferred Treatment Of HIV
Funder
National Health and Medical Research Council
Funding Amount
$1,070,331.00
Summary
Treatments for HIV represent a miraculous achievement of medical research. Global use of antiretroviral drugs has prevented substantial morbidity and mortality. However, it is unclear if these drugs should be used in people who are HIV positive with early HIV disease but no clinical symptoms. The START trial will result in a precise estimate of the risk-benefit for earlier versus later use of these treatments. It will immediately affect treatment guidelines around the world and inform future res ....Treatments for HIV represent a miraculous achievement of medical research. Global use of antiretroviral drugs has prevented substantial morbidity and mortality. However, it is unclear if these drugs should be used in people who are HIV positive with early HIV disease but no clinical symptoms. The START trial will result in a precise estimate of the risk-benefit for earlier versus later use of these treatments. It will immediately affect treatment guidelines around the world and inform future research for many years to come.Read moreRead less
Control Of Combined Simian-human Immunodeficiency Virus Infection Utilising NK Cells Mediating Antigen-specific Antibody Dependent Cellular Cytotoxicity - A Novel Vaccine Modality
Funder
National Health and Medical Research Council
Funding Amount
$432,587.00
Summary
Recently, progress was made in developing a vaccine against HIV. Our laboratory was selected to join a global collaboration trying to elucidate the key to this success. Attention has focused on non-neutralizing antibodies and our laboratory has developed a unique expertise in detecting such immune responses. This research will define, purify and manufacture these antibodies and test their ability to prevent HIV in animals with the ultimate aim of producing a vaccine for human use.
Successful HIV remission and cure, where patients can live normally without daily drug therapy and risk of transmitting infectious virus, will critically depend on understanding the mechanisms that control the expression of viral messenger RNA and proteins. This project further explores the mechanisms controling poorly understood steps in the proecssing of viral mRNA that are required for HIV protein produciton, and identifies new targets and strategies to drive HIV into permanent remission.
A Randomised Trial To Compare Dolutegravir+darunavir/r Versus Recommended Standard Of Care Antiretroviral Regimens In Patients With HIV Infection Who Have Failed Recommended First Line Therapy
Funder
National Health and Medical Research Council
Funding Amount
$2,323,209.00
Summary
Public sector programs for provision of antiretroviral drugs in developing countries need regimens of therapy that are safe, effective and simple to administer. The evidence base to support first line therapy is strong. This contrasts with a relative paucity of evidence for second regimens of therapy once first line effectiveness has been lost. This trial will address that evidential deficit and support evidence-based recommendations for global health.
Elucidating Unique Molecular Mechanisms Involved In HIV-1 Subtype C Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$710,989.00
Summary
Most people infected with human immunodeficiency virus (HIV) have subtype C virus (C-HIV) and live in Southern Africa and Central Asia. These regions are where the HIV pandemic is at its worst. However, we know very little about C-HIV. We have evidence that C-HIV evolves differently compared to other HIV-1 subtypes, which impacts the way it leads to AIDS. This project aims to characterise these unique molecular mechanisms, which may lead to vaccines and drugs that are optimised for C-HIV.
Identification And Quantification Of HIV Latency Biomarkers In The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$814,618.00
Summary
One major obstacle in curing HIV is the brain’s role as a potential reservoir of HIV infection. It is unknown if “reawakening” of HIV may lead to uncontrollable brain damage given that current antiretroviral drugs vary in their ability to treat brain infection. Not all patients have HIV brain infection so eradication therapies in themselves may be safe. We aim to identify and quantify biomarkers of HIV latency in the brain to stratify patients into these two cohorts.
It is feasible to sequence patient genomes but we need to know more about how genetic variants cause complex disease. We have sequenced genomes from patients with immune deficiency and will test the idea that genetic variation causes consistent changes in particular white blood cells, thus providing a bridge between genomic information and clinical diagnosis. Outcomes will include more accurate diagnosis, better understanding of immunity, and a strategy for using whole genome information.
Applying Quantitative Immunology To The Analysis Of Complex Genetic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$864,596.00
Summary
The immune response of each individual varies. For some, the response invoked by foreign challenge is weak, leading to a lifetime of difficulty with infection. For others, the response is stronger, yielding excellent immunity, but opening the potential for overactive responses to self-material and autoimmune disease. We have a new theory for how the health of our immune system can be measured and we aim to apply it to understand the genesis of the many different forms of human immune diseases.
The Mechanism For Combined Immunodeficiency And Autoimmunity Due To STK4-deficiency And Its Broader Application To Human PIDs
Funder
National Health and Medical Research Council
Funding Amount
$648,371.00
Summary
Why do some patients develop autoimmune diseases such as lupus where the immune system makes antibodies that attack its own body? To answer this, we plan to study a disease where a gene responsible for making antibodies is defective. Patients with mutations in the STK4 gene are unable to regulate the selection processes by which only the right cell is chosen to make antibodies. Understanding how STK4 works may help us unlock the mystery of what causes lupus.