Discovery Research|People

• Key Achievements
• Publications
• Projects
• Research Groups

• Key Achievements

  • Stephen has published over 300 scientific papers and is well recognised by his studies of T cell and antibody immunity to HIV and influenza. He has given over 100 invited talks and seminars on his research. Stephen has won multiple awards for his research and PhD supervision. He heads a large $16m NHMRC program as Chief Investigator A. He was elected to the Australian Academy of Health and Medical Sciences in 2018.

  Publications
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  Projects

  • Antibody dependent cellular cytotoxicity (ADCC) - a neglected anti-HIV immune response!

    The importance of HIV-specific Antibody-dependent Cellular Cytotoxicity (ADCC) antibodies that inhibit viral replication mediated through the Fc receptor is becoming clear. In view of the difficulty of inducing broad neutralising antibodies and effective T cell immunity, exploring HIV-specific ADCC is a priority. HIV-specific ADCC has been under-explored both from the point of view of rapid, reliable assays to measure and characterise ADCC responses and the ability to specifically induce high level HIV-specific ADCC antibodies by vaccination. Recent data from the RV144 vaccine study in Thailand suggest a role for non-neutralising antibodies in protection from HIV.

  • Combined Influenza-AIDS Vaccines

    Influenza and HIV are both serious global pathogens. Can a single vaccine be designed to cover both viruses? Recent advances in reverse genetic techniques allow insertion of foreign antigens into live influenza viruses. Further, live attenuated influenza vaccines are now highly effective vaccines. Stephen’s group is designing recombinant influenza vaccines with inserted HIV antigens to test as a combined Influenza-AIDS vaccine. An advantage of this strategy is that as a mucosal virus, there is a strong likelihood that immunity at mucosal surfaces, where HIV is first encountered, can be induced with this approach. 

  • Nanoparticle HIV vaccines

    No safe HIV vaccines have been able to stimulate durable, activated T-cell immunity. Stephen’s group is investigating an exciting HIV vaccination approach using hollow, submicron, delivery vehicles (nanocapsules) as carriers for HIV vaccines. This is a novel, cross-disciplinary project within the Australian Research Council (ARC) Centre of Excellence in Bio-Nano interactions. Nanocapsules are designed to induce optimal immune responses by protecting antigens from degradation prior to reaching sites of immune activation and activate antigen presenting cells in a way that will initiate anti-viral immune responses. Stephen’s group aims to use controlled-release nanocapsules to stimulate durable anti-HIV responses in vivo.

  • NKT cells, MAIT cells and HIV

    NKT cells are a small but very important lymphocyte population in blood that possess potent antiviral and antitumor activities. NKT cells are depleted during HIV infection. Stephen’s group are now devising strategies to enhance the biologic utility of NKT cells in fighting HIV. They are also starting to study an interesting population of cells called Mucosal-associated Invariant T cells (MAIT cells). MAIT cells are likely to be important in protecting HIV-infected people from damage at mucosal surfaces such as the gut.

  • Checkmating HIV - trapping immune escape HIV strains

    CD8+ cytotoxic T lymphocytes (CTL) can be effective at controlling HIV-1, but their utility is partly offset by mutational escape. The kinetics of CTL escape, and reversion of escape mutant viruses upon transmission to MHC-mismatched hosts can help understand CTL-mediated viral control and the fitness cost extracted by immune escape mutation. The work has implications for how best to control HIV during early infection.

  • Influenza – specific ADCC: role in a Universal Flu vaccine?

    Influenza mutates regularly to avoid neutralising antibodies. Immune responses targeting more conserved areas are needed to combat new flu pandemics. Stephen’s group have adapted and refined their HIV ADCC assays to study Influenza. They have found there is a remarkable degree of cross-reactivity in influenza ADCC immunity. They recently found that influenza ADCC can play a role in reducing the severity of the 2009 Swine Flu epidemic. The work opens up a whole new field of flu immunity. They are now studying how flu-specific ADCC can be induced by vaccination and lead to protective immunity.

  • COVID-19 monoclonal antibody 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-CoV-2, the cause of the COVID-19 illness. We have recruited blood samples from people who have recovered from COVID-19 to understand how their antibodies work to control COVID-19. Some of this work has recently been submitted for publication.  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.

  • COVID-19 specific antibody dependent cellular cytotoxicity

    Dr Wen Shi Lee, Kent Group together with Dr Amy Chung’s group are trying to understand if Fc functions of anti- SARS-CoV-2 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. Amy has recently submitted work on antibody profiling in subjects of different ages and those recovered from COVID-19.

  • HIV Vaccines

    A 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. 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.

  • Influenza immunity and novel vaccines

    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. We have series of 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.

  • Influenza B cell immunity in the lung

    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 influenza-specific B 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 improved vaccine technologies.

  • Nanoparticle Vaccine Research

    The Kent group is part of an Australian Research Council funded Centre of Excellence on nanomedicine.  They 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. Tke Kent group have collaborated widely with many of the groups within their 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 the Thordarson and Kavallaris groups. They are hosting research in the Kent laboratory from Dr David Ju of the Caruso group and they are jointly supervising Mai Vu from the Davis/Truong group at Monash for her PhD. They are actively working on liposomal, mesoporous silica templated, and self-assembling ferritin nanoparticle vaccines for influenza, HIV and SARS-CoV2.

  • COVID-19 animals models

    The Kent group are working to improve the ability to measure anto-COVID-19 immunity in ferrets together with collaborators at CSIRO. They recently developed the capacity to clone out influenza-specific monoclonal antibodies from ferrets (Wong et al Plos One, 2020 in press). They have also recently developed better reagents to study Tfh, B cells and NK cells in ferrets – these should be useful reagents to better understand immunity to SARS-CoV2 infection in ferrets.

  • COVID-19 vaccines

    A group led by Dr Adam Wheatley, Dr Jennifer Juno and Hyon-Xhi Tan are making protoype vaccines against SARS-CoV2 based on their track record in Influenza, HIV and with nanoparticles. They are comparing spike protein vs RBD protein immunisation with in-depth humoral, B cell and T cell studies in mice and larger animal models. They are developing self-assembling ferritin nanoparticle vaccines, analogous to recently published work in Influenza by Hannah Kelly and Dr Adam Wheatley. Dr Jennifer Juno is leading the work to improve antibody responses through induction of T-follicular helper responses, a critically important cell in the lymph node draining the site of vaccination.

  Research Groups

  • Kent Group

    Stephen’s group studies immunity to HIV, influenza and SARS-CoV-2. They are analysing a variety of vaccine strategies, including nanoparticle-based vaccines. They are studying a series of immune responses to gain better insights into protective immunity to important viral pathogens. They are developing monoclonal antibody therapies for HIV, influenza and SARS-CoV-2 to improve the treatment of these infections. The Kent group works very closely with Dr Amy Chung’s laboratory at the Doherty Institute.

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    Lab Team

    

    • Dr Adam Wheatley

      Laboratory Head
    • Dr Jennifer Juno

      Laboratory Head
    • Hyon-Xhi Tan

      Research Officer
    • Dr Marios Koutsakos

      Senior Research Fellow
    • Dr Wen Shi Lee

      Research Officer
    • Mai Ngoc Vu

      Postdoctoral Fellow
    • Lara Schwab

      Research Officer
    • Mitchell Zheng

      Postdoctoral Fellow
    • Rosela Webster

      Postdoctoral Fellow
    • Chris Gonelli

      Research Officer
    • Palak Mehta

      Research Officer
    • Thakshila Amarasena

      Research Support Officer
    • Andrew Kelly

      Research Assistant
    • Lauren Burmas

      Research Assistant
    • Julie Nguyen

      Research Assistant
    • Robyn Esterbauer

      Research Assistant
    • Ellie Reilly

      Research Assistant
    • Jane Batten

      Project Manager
    • Janavi Rambhatla

      Academic Specialist - Research Officer
    • Devaki Pilapitiya

      PhD Student
    • Ruth Purcell

      PhD Student (co-supervisor with Amy Chung)
    • Kirsty Field

      PhD Student
    • Thu Do

      PhD Student
    • Yee-Chen Liu

      PhD Student
    • Veronica Zoest

      PhD Student
    • Nanouk Zuidmeer

      International Masters Student Placement
    • Professor David O'Connor

      Honorary
    • Professor Shelby O'Connor

      Honorary
    • Dr David (Yi) Ju

      Honorary
    • Dr Hillary Vanderven

      Honorary
    • A/Prof Matt Parsons

      Honorary
    • Dr Nghia Truong

      Honorary
    • Dr Sinth Jegaskanda

      Honorary
    • A/Prof Steve Rockman

      Honorary
    • Dr Emily Pilkington

      Guest Scientist
    • Dr Shiyao Li

      Guest Scientist
    • Diyana Hassanel

      Guest Scientist
    • Zihnil Mazrad

      Guest Scientist

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