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Professor Stephen Kent

Professor Stephen Kent

Professor Stephen Kent

(03) 8344 9939 | [email protected]

Position:
Laboratory Head
Theme(s):
Viral Infectious Diseases, HIV, Influenza
Discipline(s):
Discovery Research, Translational and Clinical Research
Unit(s):
Department of Microbiology and Immunology (DMI)
Lab Group(s):
Kent Group

Professor Stephen Kent trained as an infectious diseases physician and viral immunologist in Melbourne and the USA. He is a National Health and Medical Research Council Senior Principal Research Fellow. Stephen heads a lab studying immunity to HIV, Influenza, COVID-19 and other variable and difficult to vaccinate against viruses. Several vaccine concepts tested in his lab have shown sufficient promise to progress into human clinical trials. Stephen remains active in infectious diseases clinical medicine at the Alfred Hospital and Melbourne Sexual Health Centre. He is proud to lead a team of gifted scientists studying viral immunity. Links to his University blog and other details of his lab can also be found here.

  • 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 groupthe Davis group, the Pu-Chun Ke group, the Johnson group, the Whittaker groupthe 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 InfluenzaHIV 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 and influenza. 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.


      Lab Team

      Kent Group

      • Dr Adam Wheatley
        Group Leader | Postdoctoral Fellow
      • Dr Amy Chung
        Group Leader | Postdoctoral Fellow
      • Jennifer Juno
        Group Leader | Postdoctoral Fellow
      • Emily Pilkington
        Postdoctoral Fellow
      • Hyon-Xhi Tan
        Postdoctoral Fellow
      • Kevin John Selva
        Postdoctoral Fellow
      • Martin Killian
        Postdoctoral Fellow
      • Dr Mingyang Wang
        Postdoctoral Fellow
      • Wen Shi Lee
        Postdoctoral Fellow
      • Ebene Haycroft
        Research Assistant
      • Ester Lopez
        Research Assistant
      • Robyn Esterbauer
        Research Assistant
      • Sriveni Pantham
        Research Assistant
      • Thakshila Amarasena
        Technical Assistant
      • Jane Batten
        Administrative Assistant
      • Hannah Kelly
        PhD Student
      • Isaac Barber-Axthelm
        PhD Student
      • Kathleen Wragg
        Research Assistant
      • Kirsty Field
        Honours Student
      • Julius Wong
        PhD Student
      • Mai Vu
        PhD Student
      • Marloes Grobben
        PhD Student
      • Matthew Worley
        PhD Student
      • Samantha Davis
        PhD Student
      • Timon Damelang
        PhD Student
      • Wenbo Jiang
        PhD Student
      • Yi Liu
        PhD Student
      • Professor David O'Connor
        Honorary
      • Dr David (Yi) Ju
        Honorary
      • Hillary Vanderven
        Honorary
      • Dr Matt Parsons
        Honorary

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