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. I completed my undergraduate studies at the University of Oviedo, Spain, and obtained my PhD at the University of Bonn, Germany. Following an extended post-doctoral stint at the Doherty Institute in Melbourne, I relocated to UNSW in 2023 to establish my own laboratory. My research studies fundamental T cell biology and T cell immunity to infectious diseases, applying this knowledge to develop experimental T cell-based vaccines in preclinical models of infection and translating these findings into human vaccines.

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

CD8⁺ T cell biology and tissue-resident T cell memory: My work on CD8⁺ T cell memory in tissues demonstrated that a subpopulation of CD8⁺ T 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 research defined liver T_RM cells as a unique subpopulation of memory cells with marked peculiarities, such as their exposure to the blood. This was followed by the identification of the Plasmodium berghei ribosomal protein RPL6 as a highly protective antigen for T_RM-based immunity against malaria (and also the cognate antigen of PbT-I cells). RPL6 was only the second Plasmodium-derived protective CD8 T cell epitope ever identified in the C57BL/6 background, enabled direct studies of endogenous liver T_RM cells specific for Plasmodium, and was essential for subsequent development of T_RM-based vaccines against malaria. 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 various adjuvants to induce liver T_RM cell formation and malaria protection. 

Development of T_RM cell-based malaria vaccines: These advances in understanding T_RM biology enabled the generation of the first T_RM-based subunit experimental vaccine against malaria, termed "Prime and Trap". This vaccine provided unprecedented protection (for a subunit vaccine) against Plasmodium liver infection in mice, proving that T_RM immunity could be efficiently harnessed for exceptional malaria protection, and delineated the requirements to induce this type of immunity. Subsequent work developed a more simple, second generation glycolipid vaccine and a third generation, mRNA-based vaccine against malaria, both based on similar principles as Prime and Trap.

Development of key scientific resources for the research of malaria immunology: The study of malaria immunology offers unique insights into fundamental mechanisms regulating T cell biology, such as T cell activation, expansion and persistence, T cell exhaustion and tissue immunity. A major challenge in this field has been the lack of adequate tools for accurately tracking T cell responses in mice. I contributed to 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 have enabled important contributions to basic immunology and malaria immunity. More recently, a cross-disciplinary approach involving mass spectrometry analyses identified the cognate Plasmodium antigens recognised by PbT-I and PbT-II cells, further enhancing the usefulness of these immunological tools.

CD4⁺ T cell biology: Using PbT-II cells, my work revealed the importance of type I dendritic cells in priming CD4⁺ T cell responses against malaria and promoting specific, polarised CD4⁺ T cell subsets. This work also demonstrated the importance of CD4⁺ T cells in licensing dendritic cells to generate CD8⁺ T cell responses, even in the presence of systemic inflammation (i.e. blood stage malaria). These findings have important implications for understanding of CD8⁺ T cell immunity and, potentially, for future immunisation strategies targeting antigen presenting cells.

Development of a COVID vaccine: I have had the opportunity to collaborate in the development of a new COVID vaccine by the Torresi lab, Doherty Institute, assessing its capacity to generate CD4 and CD8 T cell responses.