PROJECT SUMMARY Vaping is a serious public health concern that was associated with outbreaks of hospitalizations and deaths in 2019. These outbreaks of electronic vaping associated lung injury (EVALI) coincided with increased use of electronic vaping devices by adolescents and young adults. The rapid disease onset of EVALI and the role of macrophages in its progression, support a role for the innate immune system in the pathogenesis of EVALI. Despite its rising use little is currently known about the effect of vaping on pulmonary immunology and physiology highlighting the need for animal models to better understand its effects. Small animal models have shown pathologic changes following exposure to vaping aerosols; however, they do not recapitulate the pathologic manifestations of EVALI reported in humans necessitating a more translatable animal model to investigate the pathogenesis of EVALI. Nonhuman primates (NHPs) are ideally suited for studying respiratory diseases in humans due to their similarity in both pulmonary anatomy and immunology which provide advantages over other animal models. Here, we aim to utilize a NHP model to investigate the impact of vaping aerosol exposure on innate pulmonary defense mechanisms. We will longitudinally assess pulmonary and innate immune function (immune cell infiltrates, alveolar macrophage phagocytosis, and secretion of cytokines, chemokines, and defense molecules) over a four-week period of daily vaping aerosol exposure. At the end of the study, correlation with pathologic changes will occur through rigorous postmortem examination and sampling of the upper and lower respiratory tract. The data generated from this study will inform on mechanisms by which vaping aerosols effect innate pulmonary defenses, an important area of investigation in this time of highly infectious respiratory diseases. Furthermore, this study will provide preliminary data for future investigations evaluating the contribution of individual constituents within the vaping liquid (nicotine, tetrahydrocannabinol, and vitamin E acetate); and vaping in the context of comorbid conditions (SARS-CoV-2 and HIV/SIV), areas of special interest supported by several funding agencies (NIDA, NHLBI, NIAID). This proposed study and Mentored Career Development Plan will be conducted at the Tulane National Primate Research Center under the guidance of Drs. Ronald Veazey and Chad Roy. The TNPRC has been a national resource and center of excellence for biomedical research using nonhuman primates for over 50 years. The TNPRC has a strong commitment to training and mentorship and provides support (financial and effort-based) to create a rich and diverse training environment for early-stage investigators. The TNPRC fully supports Dr. Blair in his career goal to develop into an independently funded private investigator working with NHP models to study diseases of major public health importance. The dedicated time and additional mentorship provided by this K01 will help Dr. Blair refine his grant writing and project management skills to ensure the success of his future R01 proposals.

PROJECT NARRATIVE Animal models are needed to better understand the mechanisms resulting in electronic vaping associated lung injury (EVALI). Components of the innate immune system play a major role in EVALI progression in humans. Nonhuman primates are ideally suited to investigate the innate immune mechanism underlying EVALI due to their similar anatomy and immunology to humans.