Immunoengineering nanoparticles for mucosal drug and vaccine treatment of sexually transmitted infections
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Sexually transmitted infections (STIs) are a major burden on human health worldwide, accounting for nearly 1 million infections daily. Women’s sexual and reproductive health is disproportionately impacted by the most commonly transmitted pathogens, including Hepatitis B, human simplex virus (HSV), human immunodeficiency virus (HIV), and human papilloma virus (HPV). The impact of these diseases on women’s health extends from higher rates of infections to the danger of mother-to-child transmission to secondary conditions such as cervical cancer. While drugs have been developed to address symptoms, the spread of these diseases will truly be curbed with development of vaccines. Astoundingly, while nearly 30 sexually transmitted pathogens have been identified, we currently have developed vaccines to address only two of these pathogens. A key observation driving research is that effective HPV vaccines stimulate the generation of neutralizing antibodies in the genital tract. This has inspired work that is focused on evaluating administration routes, which directly allow for immunization at the site of infection. Additionally, nanomaterial carriers show great promise in the delivery of vaccine antigens after mucosal immunization. These systems allow us to specifically modify carrier composition and surface properties to deliver vaccines and drive immunogenic responses in the vaginal mucosa. In this dissertation, we leverage Bioengineering strategies to address fundamental challenges in reproductive immunology. We demonstrate that protein growth factors can be delivered vaginally to expand key immune cell populations, which play a major role in mounting protective immune responses. We build a proof-of-concept, protein-functionalized nanoparticle system to enhance transepithelial transport of nanocarriers post-vaginal delivery. Finally, we evaluate our nanoparticle systems for vaccine antigen delivery to T cells, and demonstrate the generation of functional effector T cell responses. Our research highlights the barriers to generating protective immune responses in the genital tract, and we demonstrate that biomaterials can be leveraged to address these challenges. We hope to have laid the groundwork for further investigation and validation of nanoparticle systems to engineer mucosal immune protection for application as vaccines against STIs.
- Bioengineering