Dr Adam Wheatley
Dr Wheatley leads a team studying the development and regulation of humoral immunity against viral pathogens such as influenza and SARS-CoV-2. After a PhD at the University of Melbourne, and post-doctoral training at the Vaccine Research Center, National Institutes of Health, USA, he returned to the Doherty Institute in 2015. He and his team have expertise in the design and pre-clinical testing of novel vaccine platforms, B cell immunology and the interrogation of vaccine immunity, in particular defining mechanisms to generate broad and lasting antibody-based protection against viral diseases.
Characterisation of antiviral immunity to viral infections and vaccines
The rapidly spreading global pandemic caused by SARS-CoV-2 requires an in-depth understanding of protective immunity, whether established after recovery from infection or in response to successful immunisation. Our team has made rapid contributions to the understanding of COVID-19 immunity. Using B cell probes and novel T cell assays, we recently established that the generation of neutralising antibody responses following mild to moderate COVID-19 was associated with the phenotypic makeup of circulating T follicular helper cells in the circulation of recovered individuals (link). In addition, we have undertaken an in-depth characterisation of the decay of relevant immune responses over time (link).
The effectiveness of current influenza vaccines is hampered by the marked antigenic diversity of the virus, both within and between circulating strains. This necessitates global virus surveillance and near-annual vaccine updates. Efforts to generate a “universal” influenza vaccine for broad protection against diverse influenza strains are greatly informed by the discovery of reproducible elicitation of broadly reactive antibodies in humans. In recent studies, we made use of rHA probes to interrogate the human humoral immune response to influenza. This includes characterising influenza-specific B cell responses to currently licensed seasonal vaccines and experimental pandemic vaccines.
Development and pre-clinical testing of novel vaccine technologies
There is a critical need for more efficacious vaccines against many viral pathogens such as HIV, RSV and influenza. Our lab has an interest in novel immunogen design, paired with the development of nanoparticle-based vaccine platforms, nucleic acid-based vaccines and heterologous live-attenuated influenza vaccines. We have researched prototypic vaccines against SARS-CoV-2, and have previously performed in-depth immunological characterisation of vaccine-elicited T and B cell responses in mouse and non-human primates immunised with protein subunit vaccines against SARS-CoV-2 (link). We have ongoing active projects to expand upon these preliminary findings and drive novel vaccine technologies into early phase human clinical trials, with a view to increasing the speed, magnitude, or durability of vaccine elicited immunity.
Mechanistic understanding of the immunology of vaccination
While vaccine development has historically been an empirical exercise, there is much that could be accelerated with a mechanistic understanding of the immunological factors that underpin successful vaccine outcomes. We have an interest in exploring the nature and control of B cell immunodominance hierarchies as they pertain to critical vaccine targets such as influenza HA and SARS-CoV-2 spike. In addition, we explore the regulation of germinal centre function, the interplay of B and TFH cells in lymphoid and lymphoid-like environments, and interactions of nanoparticulate vaccines with the immune system.
Isolation of human monoclonal antibodies for prophylaxis or treatment of viral infections
Human monoclonal antibodies have tremendous potential as novel agents for therapeutic treatment, or prophylaxis, of respiratory viral infections. We have previously identified broadly reactive antibodies that are reproducibly found in multiple humans and target a highly conserved stem region of the influenza A hemagglutinin. More recently, we characterised human responses to influenza B that included highly cross-reactive monoclonal antibodies with broad protective potential. Such antibodies may have utility for influenza prophylaxis, or for the clinical treatment of severe influenza infections.