We present a comprehensive vaccine strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by combining antigen optimization and nanoparticle display. We first developed a receptor binding domain (RBD)-specific antibody column for purification and displayed the RBD on self-assembling protein nanoparticles (SApNPs) using the SpyTag/SpyCatcher system. We then identified the heptad repeat 2 (HR2) stalk as a major cause of spike metastability, designed an HR2-deleted glycine-capped spike (S2GΔHR2), and displayed S2GΔHR2 on three SApNPs with high yield, purity, and antigenicity. Compared to the RBD, the RBD-ferritin SApNP elicited a more potent murine neutralizing antibody (NAb) response on par with the spike. S2GΔHR2 elicited two-fold-higher NAb titers than the proline-capped spike (S2P), while S2GΔHR2 SApNPs derived from multilayered E2p and I3-01v9 60-mers elicited up to 10-fold higher NAb titers. The S2GΔHR2-presenting I3-01v9 SApNP also induced critically needed T-cell immunity, thereby providing a next-generation vaccine candidate to battle the COVID-19 pandemic.
Background: Cardiovascular disease is a kind of comorbidity of spondyloarthritis (SpA). Hyperuricaemia is a risk factor of cardiovascular disease. Previous SpA study concerning cardiovascular disease and hyperuricaemia found that hyperuricaemia is more prevalent in radiographic SpA. Thus, we evaluated the association of serum uric acid (SUA) concentration and radiographic SpA. Methods: We made use of data from a cross-sectional study in Chinese Shenzhen Second People’s Hospital from 2016 to 2018, which included 202 SpA patients diagnosed by rheumatologists. This study detected the prevalence of comorbidities and risk factors of SpA patients. Using data from this study, we evaluated the association between radiographic images of SpA and SUA concentration. We compared the SUA concentration between radiographic SpA group and non-radiographic SpA group, with logistic regression models. Stratified and interaction analyses were also performed to further confirm the consistence of the relationship. Multiple imputation was used to deal with missing data.Results: This research studied 202 SpA patients’ data including their SUA, sacroiliac images, and other relevant laboratory data. Elevated SUA concentration was found to be associated independently with the increased risk of radiographic SpA after adjusted for confounders. The risk for developing radiographic SpA increased 13% [adjusted odds ratio (OR) = 1·13, 95% confidence interval (CI):(1·05, 1·22), p=0·0014] for per 10umol/L SUA increased. Stratified analyses, interaction analyses and multiple imputation analyses also confirmed the consistence of the association.Conclusions: Based on this Chinese population cross-sectional study, we identify that elevated SUA concentration is a risk factor for developing radiographic SpA.
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