Multipolymer microsphere delivery of SARS-CoV-2 antigens

Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective responses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric microsphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere system can preclude the need for repeat administrations, highlighting its potential as an effective vaccine. Statement of significance Successful SARS-CoV-2 vaccines were developed and quickly approved by the US Food and Drug Administration (FDA). However, each of the vaccines requires boosting as new variants arise. We posit that injectable biodegradable polymers represent a means for the sustained release of emerging viral antigens. The approach offers a means to reduce immunization frequency by predicting viral genomic variability. This strategy could lead to longer-lasting antiviral protective immunity. The current proof-of-concept multipolymer study for SARS-CoV-2 achieve these metrics. [PDF also includes a graphical abstract that can not be displayed here.

Master of Science

thesisCoevolution occurs when different species affect each other's evolution, which can drive major evolutionary trends. Host-parasite systems are a model for coevolution studies, and the rock pigeon (Columba livia) - feather louse (Columbicola) system is a particularly useful model system because it is relatively easy to observe, mark, and quantify these permanent, obligate ectoparasites. Many life history traits have been examined in this system, such as the effect of body size, temperature, humidity, and fecundity. However, there are still life history traits critical to understanding adaptation in these lice that have not yet been examined. In this thesis, I examine generation time, mechanisms of endosymbiont transfer, and the effects of divergence on lice in the genus Columbicola. In Chapter 1, I provide a brief overview to this system, and an outline of my experiments. In Chapter 2, I investigate the generation time of Columbicola columbae lice on their host and compare it to a previous in vitro study of generation time. I found the generation time on the host to be 22 days. Generation time is an important life history trait that affects the population dynamics and evolution of a species. In Chapter 3, I investigate a potential mechanism for the transfer of endosymbionts between two different species of lice, Columbicola columbae and Columbicola tschulyschman. I found that these two species do mate when they are in contact, but they do not produce hybrid offspring. In Chapter 4, I investigate if divergent selection for body color in Columbicola columbae lice inadvertently leads to reproductive iv isolation, as is found with divergent selection on louse body size. I did not find any evidence of reproductive isolation between lineages of lice that had undergone divergent selection for colo

Accelerated Neuroimmune Dysfunction in Aged HIV-1-Infected Humanized Mice

Disordered immunity, aging, human immunodeficiency virus type one (HIV-1) infection, and responses to antiretroviral therapy are linked. However, how each factor is linked with the other(s) remains incompletely understood. It has been reported that accelerated aging, advanced HIV-1 infection, inflammation, and host genetic factors are associated with host cellular, mitochondrial, and metabolic alterations. However, the underlying mechanism remains elusive. With these questions in mind, we used chronically HIV-1-infected CD34-NSG humanized mice (hu-mice) to model older people living with HIV and uncover associations between HIV-1 infection and aging. Adult humanized mice were infected with HIV-1 at the age of 20 weeks and maintained for another 40 weeks before sacrifice. Animal brains were collected and subjected to transcriptomics, qPCR, and immunofluorescence assays to uncover immune disease-based biomarkers. CD4+ T cell decline was associated with viral level and age. Upregulated C1QA, CD163, and CXCL16 and downregulated LMNA and CLU were identified as age-associated genes tied to HIV-1 infection. Ingenuity pathway analysis affirmed links to innate immune activation, pyroptosis signaling, neuroinflammation, mitochondrial dysfunction, cellular senescence, and neuronal dysfunction. In summary, CD34-NSG humanized mice are identified as a valuable model for studying HIV-1-associated aging. Biomarkers of immune senescence and neuronal signaling are both age- and virus-associated. By exploring the underlying biological mechanisms that are linked to these biomarkers, interventions for next generation HIV-1-infected patients can be realized