Formulation of SARS-CoV-2 Spike Protein with CpG Oligodeoxynucleotides and Squalene Nanoparticles Modulates Immunological Aspects Following Intranasal Delivery.

Nasal spray vaccination is viewed as a promising strategy for inducing both mucosal and systemic protection against respiratory SARS-CoV-2 coronavirus. Toward this goal, a safe and efficacious mucosal adjuvant is necessary for the transportation of the antigen across the mucosal membrane and antigen recognition by the mucosal immune system to generate broad-spectrum immune responses. This study describes the immunological aspects of SARS-CoV-2 spike (S)-protein after being formulated with CpG oligodeoxynucleotides (ODNs) and squalene nanoparticles (termed PELC). Following intranasal delivery in mice, higher expression levels of major histocompatibility complex (MHC) class II and costimulatory molecules CD40 and CD86 on CD11c+ cells were observed at the draining superficial cervical lymph nodes in the CpG-formulated S protein group compared with those vaccinated with S protein alone. Subsequently, the activated antigen-presenting cells downstream modulated the cytokine secretion profiles and expanded the cytotoxic T lymphocyte activity of S protein-restimulated splenocytes. Interestingly, the presence of PELC synergistically enhanced cell-mediated immunity and diminished individual differences in S protein-specific immunogenicity. Regarding humoral responses, the mice vaccinated with the PELC:CpG-formulated S protein promoted the production of S protein-specific IgG in serum samples and IgA in nasal and bronchoalveolar lavage fluids. These results indicate that PELC:CpG is a potential mucosal adjuvant that promotes mucosal/systemic immune responses and cell-mediated immunity, a feature that has implications for the development of a nasal spray vaccine against COVID-19.

Alteration in angiotensin-converting enzyme 2 by PM1 during the development of emphysema in rats.

INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) provides an adhesion site for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with COPD could have severe outcomes after SARS-CoV-2 infection. The objective of this study was to investigate ACE2 regulation by air pollution during the development of COPD. METHODS: Sprague Dawley rats were exposed to unconcentrated traffic-related air pollution for 3 and 6 months. We examined lung injury markers, oxidative stress, inflammation, emphysema, ACE2 and angiotensin II receptor type 1 (AT1) and 2 (AT2) in the lungs after exposure. RESULTS: Lung injury occurred due to an increase in permeability and lactate dehydrogenase cytotoxicity was observed after 6 months of exposure to fine particulate matter of <1 µm in aerodynamic diameter (PM1). An α1-antitrypsin deficiency and neutrophil elastase production with emphysema development were observed after 6 months of PM1 exposure. 8-isoprostane and interleukin-6 were increased after 3 and 6 months of PM1 exposure. Caspase-3 was increased after exposure to PM1 for 6 months. Upregulation of ACE2 was found after 3 months of PM1 exposure; however, ACE2 had decreased by 6 months of PM1 exposure. AT1 and AT2 had significantly decreased after exposure to PM1 for 6 months. Furthermore, smooth muscle hypertrophy had occurred after 6 months of PM1 exposure. CONCLUSIONS: In conclusion, short-term exposure to PM1 increased the ACE2 overexpression in lungs. Long-term exposure to PM1 decreased the ACE2 overexpression in emphysema. Air pollution may be a risk for SARS-CoV-2 adhesion during the development of COPD.