Head of Unit
Pandemic Coronavirus research
From early 2020 the Kent lab is now urgently working on the pandemic coronavirus. We are taking our knowledge on immunity to HIV and Influenza and applying it to develop antibody treatments and vaccines for SARS-CoV2, the cause of the COVID-19 illness. We are recruiting blood samples from people who have recovered from COVID-19 to understand how their antibodies work to control COVID-19. This research, led by Adam Wheatley, aims to generate monoclonal antibodies as a potential therapy or prophylaxis for COVID-19. Our work on generating monoclonal antibodies against influenza provides a sound basis for this.
Dr Wen Shi Lee in our group together with Dr Amy Chung’s group are trying to understand if Fc functions of anti- SARS-CoV2 antibodies play a role in assisting immunity or not – this is an area we have extensively worked on for HIV and Influenza. We are attempting to dissect the role of prior human coronavirus infection on subsequent immunity to COVID-19.
We are also making protype vaccines against SARS-CoV2 based on our track record in Influenza, HIV and with nanoparticles. We are developing self-assembling ferritin nanoparticle vaccines, analogous to our recently published work in Influenza, and are testing them in the laboratory. We plan to improve antibody responses through induction of T-follicular helper responses, a critically important cell in the lymph node.
In Australia, the ferret may prove to be a useful model for SARS-CoV2 infection, as it is for Influenza. We are working to improve the ability to measure anto-COVID-19 immunity in ferrets together with collaborators at CSIRO.
Cellular immunity also likely plays a role in controlling COVID-19. We are studying both conventional and unconventional T cell responses in PBMC from subjects who have recovered from COVID-19 in work led by Dr Jen Juno. Jen leads a group with a strong record in studying T cell responses to HIV, Tb and Influenza, including MAIT cells, CD1-restricted cells and gamma-delta T cells.
An HIV vaccine is urgently needed. The Kent lab is working towards this goal. Our dedicated staff and students drive innovation and new thinking in ways to tackle the HIV/AIDS epidemic.
The HIV pandemic continues to expand rapidly around the world, notably in the Asia-Pacific and Africa. Public health and economic burdens of HIV represents a major threat to regional and global security. Preventative strategies remain limited, and therapeutic options are restricted in both efficacy and implementation. The lack of an effective HIV vaccine is a catastrophic failure of our public health response to the epidemic.
Better strategies are needed to prevent HIV infection and disease. This requires an understanding of how HIV causes AIDS, including which immune responses control HIV replication and which contribute to disease. A better understanding of effective immunity will expand the pipeline to novel treatment and prevention strategies.
Despite the clear need, development of HIV-1 vaccines has proceeded for 20+ years without success. HIV has a propensity to mutate to avoid immune responses and form latent reservoirs – these are formidable challenges to developing successful vaccines. There is a palpable sense in the HIV vaccine research community that fresh innovative ideas are needed. Quantum leaps away from existing paradigms will be needed to make large inroads into defining protective immunity to HIV-1.
To further understand how immune responses can control HIV, we have a series of projects involved in developing new assays to measure immunity and the effect these immune responses have on the virus. We have extensively studied antibody dependent cellular cytotoxicity (ADCC), which appears to play a role in vaccine-induced immunity to HIV. We are also trying to understand how neutralising antibodies that have ADCC activity can control HIV. We have ongoing projects led by Dr Jen Juno studying small but important lymphocyte populations such as T-follicular helper cells, gamma-delta T cells, MAIT cells and NKT cells. In work with European collaborators, we are now studying multivalent HIV-1 Env based SOSIP trimer vaccine strategies.
Seasonal Influenza continues to extract a huge toll on the community and there is the ever-present threat of new pandemics. Led by Dr Adam Wheatley, we are making headway into improving our understanding of influenza immunity with a view to improving vaccines. Current vaccines are imperfect and often target variable regions of the virus which “drift” away from effective immunity each winter. We are focussing on improving immunity, both antibodies and CD4 T cell helper cells (“Tfh”) to conserved parts of influenza, including the stem of HA. We also have a major interest in improving ADCC antibodies against influenza. The group has had a major push to understand and improve immunity to Influenza type B viruses and we have now generated panels of monoclonal antibodies that target this virus.
Cells in the lung, both T cells and B cells, appear to be important in immunity to repeated infection with influenza. Led by Dr Hyon-Xhi Tan, we are starting to understand how immune cells lodge and organise themselves in the lung and fight off new influenza virus infection.
Our understanding of immune responses against Influenza allows us to push on with developing novel vaccine technologies. In particular we have exciting projects studying nanoparticle vaccines where tiny capsules are loaded with vaccine antigens to protect them from degradation and target important immune cells that stimulate effective immunity.
Nanoparticle Vaccine Research
The Kent group is part of an Australian Research Council funded Centre of Excellence on nanomedicine. We have a series of work studying how small particles “nanoparticles” interact with the immune system and how this could be exploited in the future as vaccines or therapies. We have collaborated widely with most of the groups within our centre, including the Caruso group, the Crampin group, the Davis group, the Pu-Chun Ke group, the Johnson group, the Whittaker group, the Thurecht group, and more recently the Thordarson and Kavallaris groups. We are hosting research in our lab from Dr David Ju of the Caruso group and we are jointly supervising Mai Vu from the Davis/Truong group at Monash for her PhD. We are actively working on self-assembling ferritin nanoparticle vaccines and liposome based vaccines for influenza, HIV and SARS-CoV2.