Inhalable SARS-CoV-2 vaccines for single-dose dry-powder aerosol immunization and orchestrated mucosal/systemic immune responses (preprint)

The ongoing coronavirus disease pandemic has fostered major advances in vaccination technologies; however, there are urgent needs of mucosal immune responses and single-dose, non-invasive administration. Here, we develop a SARS-CoV-2 vaccine for single-dose, dry-powder aerosol inhalation that induces potent systemic and mucosal immune responses. Our vaccine encapsulates proteinaceous cholera toxin B subunit-assembled nanoparticles displaying the SARS-CoV-2 RBD antigen (R-CNP) within microcapsules of optimal aerodynamic size, and such unique nano-micro coupled structure supports efficient alveoli delivery, sustained R-CNP release, and antigen presenting cell uptake, which are favorable for invocation of immune responses. Moreover, our vaccine successfully induces robust serological IgG and secretory IgA production, collectively conferring effective protection from SARS-CoV-2 challenge (including pseudovirus and the authentic virus) in mice, hamsters, and non-human primates. Finally, we also demonstrate a “mosaic iteration” of our vaccine that co-displays ancestral and Omicron’s antigens, thus extending the breadth of antibody response against co-circulating strains and transmission of Omicron variant. These findings support our inhalable vaccine as a promising candidate to prevent SARS-CoV-2 infection, disease, and transmission.

Urine Proteome of COVID-19 Patients (preprint)

The atypical pneumonia (COVID-19) caused by SARS-CoV-2 is an ongoing pandemic and a serious threat to global public health. The COVID-19 patients with severe symptoms account for a majority of mortality of this disease. However, early detection and effective prediction of patients with mild to severe symptoms remains challenging. In this study, we performed proteomic profiling of urine samples from 32 healthy control individuals and 6 COVID-19 positive patients (3 mild and 3 severe). We found that urine proteome samples from the mild and severe COVID-19 patients with comorbidities can be clearly differentiated from healthy proteome samples based on the clustering analysis. Multiple pathways have been compromised after the COVID-19 infection, including the dysregulation of immune response, complement activation, platelet degranulation, lipoprotein metabolic process and response to hypoxia. We further validated our finding by directly comparing the same patients' urine proteome after recovery. This study demonstrates the COVID-19 pathophysiology related molecular alterations could be detected in the urine and the potential application of urinary proteome in auxiliary diagnosis, severity determination and therapy development of COVID-19.