Dr Daniel Fernandez Ruiz

I am a cellular immunologist specialised in vaccine development at the School of Biomedical Sciences, UNSW, and the UNSW RNA Institute. Originally from Spain, where I completed my undergrad studies, I obtained my PhD at the University of Bonn, in Germany, and did my post-doc at the Doherty Institute in Melbourne. I relocated to UNSW in 2023 to start my own lab. My research studies fundamental T cell biology and T cell immunity to infectious diseases, and applies this knowledge to the development of experimental T cell-based vaccines in preclinical models of infection, as well as to translation into human vaccines.

During my scientific career, I have made different contributions to the research fields of T cell biology, malaria immunology and vaccine development:

Development of key scientific resources for the research of malaria immunology: The study of malaria immunology provides unique opportunities to lear about fundamental mechanisms regulating T cell biology; for example, T cell activation, expansion and persistence, T cell exhaustion, tissue immunity, etc. A major obstacle to research on malaria immunology in mice has been the lack of adequate tools that enable accurate tracking of T cell responses. My work resulted in the development of the first Plasmodium-specific, MHC I-restricted and MHC II-restricted T cell receptor transgenic mouse lines (termed PbT-I and PbT-II respectively), which are currently employed in many laboratories around the globe and have enabled important contributions to the fields of basic immunology and malaria immunity. Importantly, more recently, using a cross-disciplinary approach involving mass spectrometry analyses, I identified the cognate Plasmodium antigens recognised by PbT-I and PbT-II cells, which further enhances the usefulness of these immunological tools.

CD8⁺ T cell biology and tissue-resident memory: My work studying CD8⁺ T cell memory in tissues demonstrated that a subpopulation of CD8⁺ cells in the mouse liver are true resident memory cells, described the transcriptional and surface marker profile of these cells and performed their functional characterisation. This thorough analysis defined liver T_RM cells as a unique subpopulation of memory cells with marked peculiarities (such as their exposure to the blood) even among T_RM cells in other tissues, and is essential for our understanding of these cells and their potential for immunity against liver infections. This work was followed up by the identification of the Plasmodium berghei ribosomal protein RPL6 as a highly protective antigen for T_RM-based immunity against malaria (this is also the cognate antigen of PbT-I cells). This was only the second Plasmodium-derived protective CD8 T cell epitope ever identified in the C57BL/6 background, which enabled the first direct study of endogenous liver T_RM cells specific for Plasmodium, and was essential for the development of T_RM-based vaccines against malaria in the lab (see below). My research also explored the requirements for the establishment and maintenance of CD8⁺ T cell resident memory in the liver, and also the capacity of a broad variety of adjuvants, either naked or aided by cell-delivery mechanisms, to induce formation of liver T_RM cells and malaria protection. 

Development of T_RM cell-based malaria vaccines: My work led to the generation of the first T_RM-based subunit experimental vaccine against malaria, termed "Prime and Trap", which provided unprecedented protection (for a subunit vaccine) against Plasmodium liver infection in mice. This vaccine provided proof of principle that T_RM immunity could be efficiently harnessed for outstanding protection against malaria, delineating the requirements to induce this type of immunity. It was followed up by a more simple, second generation glycolipid vaccine and a third generation, mRNA-based vaccine against malaria, whose efficacy relies on the same principles as Prime and Trap.

CD4⁺ T cell biology: My studies using PbT-II cells have underlined the importance of type I dendritic cells in priming CD4⁺ T cell responses against malaria and in favouring the generation of particular, polarised CD4⁺ T cell subsets. In turn, this work also demonstrated the important role of CD4⁺ T cells in licensing dendritic cells to enable the generation of CD8⁺ T cell responses, even in the presence of systemic inflammation (i.e. blood stage malaria). This finding has important implications for the understanding of CD8⁺ T cell immunity and, potentially, for future implementation of immunisation strategies that seek to deliver antigen to antigen presenting cells.

Development of a COVID vaccine: I have had the opportunity to participate in the development of a new COVID vaccine, assessing the capacity of this vaccine to generate T cell responses (CD4 or CD8) .