Background. The Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins. Method. We conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 μg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 μg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 μg of UB-612 (n = 3,875, 18–85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose. Results. No vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs. Conclusion. UB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines. Trial Registration. ClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742. Funding. UBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

This study aimed to investigate the rate of fluconazole-non-susceptible Cryptococcus neoformans in Southern Taiwan for the period 2001–2012 and analyze the risk factors for acquiring it among patients with invasive cryptococcosis. All enrolled strains were isolated from blood or cerebrospinal fluid samples of the included patients. If a patient had multiple positive results for C. neoformans, only the first instance was enrolled. Susceptibility testing was performed using the Clinical and Laboratory Standards Institutes M27-A3 broth micro-dilution method. The MIC interpretative criteria for susceptibility to fluconazole were ≤8 μg/ml. A total of 89 patients were included. Patients (n = 59) infected by fluconazole-susceptible strains were compared with those (n = 30) infected by non-susceptible strains. The patients’ demographic and clinical characteristics were analyzed. The rate of fluconazole-non-susceptible C. neoformans in the study period significantly increased over time (p < 0.001). The C. neoformans isolated in 2011–2012 (odds ratio: 10.68; 95 % confidence interval: 2.87-39.74; p < 0.001) was an independent predictive factor for the acquisition of fluconazole-non-susceptible C. neoformans. The rate of fluconazole-non-susceptible C. neoformans has significantly increased recently. Continuous and large-scale anti-fungal susceptibility tests for C. neoformans are warranted to confirm this trend.

Two-stage reimplantation arthroplasty is one of the standard treatments for chronic periprosthetic joint infection (PJI). Scanty data exist regarding the risk factors for failure after two-stage reimplantation for periprosthetic hip infection. The purpose of this study was to investigate and identify the risk factors associated with failure after two-stage reimplantation hip arthroplasty. Sixty-two patients with hip PJI treated with a two-stage reimplantation protocol at our institution from 2005 to 2012 were reviewed. Patients requiring medical treatment or reoperation for recurrent infection were defined as treatment failure. A multivariate Cox proportional hazards model was used to analyze the risk factors associated with treatment failure. Of the 62 patients, 11 (17.7%) patients had developed reinfection after the two-stage reimplantation with a mean follow-up of 5.7 years. The implant survival was 82.2% (95% confidence interval [CI] 75.19−92.55) at 10 years. Multivariate analysis revealed BMI ≥30 kg/m2 (hazard ratio [HR] 9.16; 95% CI 1.51−55.3; p = 0.0158), liver cirrhosis (HR 6.39; 95% CI 1.09−37.4; p = 0.0398), gram-negative organism (HR 5.68; 95% CI 1.18−27.4; p = 0.0303), and presence of sinus tract (HR 18.2; 95% CI 2.15−153; p = 0.0077) as the independent risk factors for treatment failure. We found obesity, liver cirrhosis, gram-negative organism, and the presence of sinus tract were significantly related to the risks of failure after reimplantation arthroplasties.

This study aimed to determine the predictors of persistent candidemia and examine the impact of biofilm formation by Candida isolates in adult patients with candidemia. Of the adult patients with candidemia in Kaohsiung Chang Gung Memorial Hospital between January 2007 and December 2012, 68 case patients with persistent candidemia (repeated candidemia after a 3-day systemic antifungal therapy) and 68 control patients with non-persistent candidemia (Candida clearance from the bloodstream after a 3-day systemic antifungal therapy) were included based on propensity score matching and matching for the Candida species isolated. Biofilm formation by the Candida species was assessed in vitro using standard biomass assays. Presence of central venous catheters (CVCs) at diagnosis (adjusted odd ratio [AOR], 3.77; 95% confidence interval [CI], 1.09–13.00, p = 0.04), infection with higher biofilm forming strains of Candida species (AOR, 8.03; 95% CI, 2.50–25.81; p < 0.01), and receipt of suboptimal fluconazole doses as initial therapy (AOR, 5.54; 95% CI, 1.53–20.10; p < 0.01) were independently associated with persistent candidemia. Biofilm formation by Candida albicans, C. tropicalis, and C. glabrata strains was significantly higher in the case patients than in the controls. There were no significant differences in the overall mortality and duration of hospitalization between the two groups. Our data suggest that, other than presence of retained CVCs and use of suboptimal doses of fluconazole, biofilm formation was highly associated with development of persistent candidemia.

Klebsiella pneumoniae (KP), with production of abundant capsular polysaccharide (CPS), is capable of causing invasive syndrome. Environmental glucose stimuli may increase CPS biosynthesis. We aimed to investigate the relationship between glycemic control and KP-mediated invasive syndrome in diabetic patients and the effect of glucose on CPS biosynthesis. Diabetic patients with community-acquired KP bacteremia were included to study the risk factors of invasive syndrome. KP-M1, a serotype-K₁ KP clinical isolate, was used to examine the CPS biosynthesis and cps gene expression, and the effect of exogenous glucose on bacterial phagocytosis and killing. We found that invasive syndrome was significantly more common in diabetic patients who were infected with strains expressing the K₁ serotype (adjusted odds ratio [AOR], 8.32; 95% confidence interval [CI], 1.56−44.24; p=0.01), and had poor glycemic control (HbA_1c ≥9%; AOR, 5.66; 95% CI, 2.01−15.92; p<0.01). Pre-incubation of KP-M1 in media containing different gradient glucose concentrations enhanced CPS biosynthesis and cps gene expression in high glucose (0.5%) concentration, which leads to increasing bacterial resistance to phagocytosis and killing. High glucose levels reflected by poor glycemic control may stimulate CPS biosynthesis and cps gene expression of highly virulent KP, which increase resistance to phagocytosis and contribute to development of invasive syndrome.