@article{Biomaterials:3676,
      recid = {3676},
      author = {Ajit, Jainu},
      title = {Engineering the Innate Immune Response Using Novel  Conjugates and Biomaterials},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2022-03},
      pages = {154},
      abstract = {Vaccines are one of the most significant scientific  discoveries allowing reduction and almost complete  eradication of deadly diseases such as smallpox and polio.  As diseases continue to emerge, we must develop ways to  produce effective vaccines faster. The quality and  magnitude of most vaccines can be modulated by targeting  the innate immune system. To do this, we need a better  understanding of the pathways regulating innate immunity.  My work focuses on improving the innate immune system  through two ways: the design of novel conjugates targeting  multiple innate immune receptors and the design of novel  biomaterials to control innate immune memory or trained  immunity. Vaccines use adjuvants to improve the immune  response towards the antigen of interest. Adjuvants  targeting multiple innate immune receptors produce distinct  responses capable of modulating downstream adaptive  immunity. However, there is a gap in mechanistic  understanding of multi- TLR agonists, limiting their use as  adjuvants. In chapter 2, I will discuss the mechanism of  action of novel covalently linked TLR agonist dimers.  Similarly, antigen-adjuvant conjugates offer promising ways  to ensure co-delivery and effective innate immune cell  activation leading to better downstream adaptive immune  responses. In chapter 3, I describe the design of a novel  antigen-adjuvant conjugate with improved CD8+ T-cell  responses in mice. 
An alternate method of targeting innate  immunity to improve overall disease resistance involves  inducing non-specific memory referred to as trained  immunity. Existing training methods do not offer temporal  control, potentially leading to uncontrolled inflammation  in certain populations. In chapter 4, I discuss the design  and application of a novel biomaterial for the temporal  control of trained immunity using a sustained release  mechanism. Finally, in chapter 5, I discuss our recent  findings on the impact of trained immunity in improving  antigen-specific antibody responses. Taken together, these  chapters demonstrate two new avenues that make trained  immunity an exciting tool for developing novel  prophylactics for overall disease resistance and improved  responses to vaccinations.},
      url = {http://knowledge.uchicago.edu/record/3676},
      doi = {https://doi.org/10.6082/uchicago.3676},
}