(2fz) Leveraging Immunoengineering for Vaccine and Therapeutics Design

The rapid evolution of viruses like influenza, HIV and SARS-CoV-2 represents a serious public health concern. Vaccine-induced immunity is unlikely to confer protection when a novel virus acquires the ability of sustained human-to-human transmission. Such risks highlight the importance of pandemic preparedness and the need to generate universal vaccine candidates that protect against diverse viral variants.

My future research program aims to combine molecular design with engineering approaches to create universal vaccine candidates that immunofocus on evolutionarily conserved regions to confer broad, durable and protective immunity. By fine-tuning the molecular architecture of antigens, I aim to understand the underlying mechanism of immunodominance, which will allow us to overcome immune imprinting, therefore directing immune responses to important epitopes of interest that afford breadth and protection.

On the other hand, viruses are prime examples of targeted cargo delivery, whereas synthetic nanomaterials have not been able to replicate the same delivery efficiency with precision. In another research program, I plan to take inspiration from viral infection and design biomimetics of viral fusogens as targeting modalities for drug delivery. I also aim to create versatile delivery vehicles for diverse therapeutic modalities using protein-based materials that are genetically encoded with high homogeneity.

Research Experience

Postdoctoral Research at Department of Biochemistry, Stanford University School of Medicine

Advisor: Professor Peter S. Kim

Vaccines are one of the most profound accomplishments of biomedical science. Despite the success, the continuous emergence of new viral variants underscores the risk of potential pandemics and emphasizes the urgency of developing universal vaccines that confer broad and durable protection against rapidly evolving viruses.

My postdoctoral research focuses on the rational design of universal vaccine candidates against Influenza and Ebola. In the case of influenza, current vaccines elicit immunity to the variable head region of hemagglutinin, the viral glycoprotein that evolves continuously. By contrast, the stem region has evolutionarily conserved regions and represents a prime target for universal flu-vaccine design, but it remains immunosilent. To address this immunological bias, I introduced a new immunofocusing strategy, antigen reorientation, to present antigens in a predefined manner. I reoriented hemagglutinin in an “upside down” configuration to sterically occlude the head region and expose the stem region, thereby redirecting antibody responses to the stem and thus promoting cross-reactivity against diverse influenza subtypes. In the case of Ebola, I harnessed hyperglycosylation as the immunofocusing strategy and created hyperglycosylated antigens that skewed immune responses toward conserved antigenic regions. These antigens induced cross-reactive immunity in animals against all three Ebola species that are pathogenic to humans.

Graduate Research at Department of Chemical and Biomolecular Engineering, University of California, Los Angeles

Advisor: Professor Yunfeng Lu

Protein therapeutics perform versatile biological functions and represent a robust medical treatment, but safe and efficient delivery is essential to unleash their therapeutic power. During my graduate research, I focused on implementing engineering tools with materials design to address the challenges in drug delivery and protein therapy. I devised various protein nanocapsules using customized chemistry that respond to physiological cues for targeted delivery purposes. In particular, I designed nanocapsules containing nerve growth factors that could penetrate the blood-brain barrier to treat central nervous system diseases and injuries. My research experience provided me with extensive skills in bioconjugate chemistry, materials design and characterization, and animal surgeries. The interplay among these disciplines enabled me to expand the toolkits for drug delivery.

First-author Publications

1. Xu D, et al. & Kim PS, Designing epitope-focused vaccines via antigen reorientation. bioRxiv (2022), DOI: 10.1101/2022.12.20.521291.
2. Xu D, et al. & Kim PS, Generating an epitope-focused Ebola vaccine candidate via immunofocusing. (in preparation)
3. Xu D, et al. & Lu Y, Efficient delivery of nerve growth factors to the central nervous system for neural regeneration. Advanced Materials (2019), 31, 1900727.
4. Wu D*, Qin M*, Xu D*, et al. & Lu Y, A bioinspired platform for effective delivery of protein therapeutics to the central nervous system. Advanced Materials (2019), 31, 1807557. (*Co-first authors)
5. Xu D, et al. & Lu Y, A hepatocyte-mimicking antidote for alcohol intoxication. Advanced Materials (2018), 30, 1707443.

Google Scholar profile: https://bit.ly/3lYosWF

Selected Awards

• Postdoctoral Fellowship, Stanford Maternal and Child Health Research Institute, 2021
• Graduate Student Award (Gold), Materials Research Society, 2020
• Outstanding Ph.D. in Chemical Engineering Award, UCLA, 2019

Teaching Experience & Interests

During my PhD training at UCLA, I served as a Teaching Assistant for two lectures, Chemical Reaction Engineering (undergraduate level) and Polymer Processes (undergraduate/graduate level). I also served as a Teaching Assistant for General Chemistry Laboratories during my master’s at Washington University. There I gained certificates for “Writing a teaching philosophy statement” and “Creating a teaching portfolio” from the Center for Teaching and Learning. My experiences and training in teaching have equipped me to teach various courses and laboratories in chemistry, chemical and biomedical engineering, biomaterials, infectious diseases, and relevant fields.

I am passionate about helping students develop skills in active learning and critical thinking, as well as the ability to integrate different disciplines into solving real-world problems. I have witnessed the impact of these skills myself, and I am motivated to continue teaching and training the next generation of scientists and engineers. I am committed to providing students with the tools and knowledge to succeed in their career paths.