Viral and Vaccine Immunology Lab
Melbourne VIC Australia
What we do
We are interested in understanding the serological and cellular responses that underpin protective immunity to viral infections, with particular focus upon SARS-CoV-2, influenza, and HIV. Our work spans human clinical studies, pre-clinical vaccine development and fundamental immunological studies in small animal models of infection and vaccination.
SARS-CoV-2 and COVID-19
From early 2020 the lab pivoted to working on the pandemic coronavirus. Building upon techniques and scientific knowledge gained studying immunity to HIV and influenza, we are now applying it to develop antibody treatments and vaccines for SARS-CoV2, the cause of the COVID-19. We have been recovering clinical samples from people who have recovered from COVID-19, or who have been immunised with COVID vaccines, to better understand how their immune systems work to best prevent or control COVID-19.
Adam Wheatley is leading work 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.
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Jen Juno is leading work to characterise CD4 T cell responses to SARS-CoV-2 and other coronaviruses. Most recently, she and Marios Koutsakos have been studying the dynamics of T cell recall during breakthrough infection. Much of our work on vaccine-induced CD4 T cell responses to SARS-CoV-2 is based on similar studies that Adam, Jen and Hyon-Xhi conducted examining T-follicular helper responses in influenza.
Hyon-Xhi Tan and Adam are making prototype 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.
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Wen Shi Lee in our group together with 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.
Influenza
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.
iBALT formation in the lungs following influenza infection
Credit: Hyon-Xhi Tan
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.
Epithelial localization of HIV-specific CD8 T cells (red/green composite cells) Credit: Hyon-Xhi Tan
HIV
An HIV vaccine is urgently needed. Led by Prof Kent, our dedicated staff and students drive innovation and new thinking in ways to tackle the HIV/AIDS epidemic.
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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.
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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.
Nanoparticle Vaccines
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.
![blood vessel1_003[1].tiff](https://static.wixstatic.com/media/5d7f11_08d4f302fc8b4444bc1646008d4f5e83~mv2.png/v1/crop/x_172,y_59,w_1190,h_1277/fill/w_338,h_363,al_c,q_85,usm_0.66_1.00_0.01,enc_avif,quality_auto/blood%20vessel1_003%5B1%5D_tiff.png)
In vitro cultured blood vessels with endothelial cell lining (cell nucleus in blue, adherens junctions in red)
Credit: Mai Vu