Safety and immunogenicity of a heterologous booster with an RBD virus-like particle vaccine following two- or three-dose inactivated COVID-19 vaccine.

LYB001 is an innovative recombinant SARS-CoV-2 vaccine that displays a repetitive array of the spike glycoprotein's receptor-binding domain (RBD) on a virus-like particle (VLP) vector to boost the immune system, produced using Covalink plug-and-display protein binding technology. LYB001's safety and immunogenicity were assessed in 119 participants receiving a booster with (1) 30 µg LYB001 (I-I-30 L) or CoronaVac (I-I-C), (2) 60 µg LYB001 (I-I-60 L) or CoronaVac in a ratio of 2:1 after two-dose primary series of inactivated COVID-19 vaccine, and (3) 30 µg LYB001 (I-I-I-30 L) after three-dose inactivated COVID-19 vaccine. A well-tolerated reactogenicity profile was observed for LYB001 as a heterologous booster, with adverse reactions being predominantly mild in severity and transient. LYB001 elicited a substantial increase in terms of the neutralizing antibody response against prototype SARS-CoV-2 28 days after booster, with GMT (95%CI) of 1237.8 (747.2, 2050.6), 554.3 (374.6, 820.2), 181.9 (107.6, 307.6), and 1200.2 (831.5, 1732.3) in the I-I-30 L, I-I-60 L, I-I-C, and I-I-I-30 L groups, respectively. LYB001 also elicited a cross-neutralizing antibody response against the BA.4/5 strain, dominant during the study period, with GMT of 201.1 (102.7, 393.7), 63.0 (35.1, 113.1), 29.2 (16.9, 50.3), and 115.3 (63.9, 208.1) in the I-I-30 L, I-I-60 L, I-I-C, and I-I-I-30 L groups, respectively, at 28 days after booster. Additionally, RBD-specific IFN-γ, IL-2, IL-4 secreting T cells dramatically increased at 14 days after a single LYB001 booster. Our data confirmed the favorable safety and immunogenicity profile of LYB001 and supported the continued clinical development of this promising candidate that utilizes the VLP platform to provide protection against COVID-19.

Yogliptin monotherapy in type 2 diabetes: A 12-week randomized, double-blind, placebo-controlled phase II study.

BACKGROUND: The new xanthine dipeptidyl peptidase-4 inhibitor yogliptin has exhibited excellent hypoglycemic activity in experimental disease models. The present work aimed to assess the efficacy of yogliptin as a monotherapy in individuals with type 2 diabetes mellitus (T2DM). METHODS: A 12-week, double-blind, placebo-controlled phase II study was performed. T2DM patients (new diagnosis or inadequately controlled) were randomly divided into groups (1:1:1:1) and administered either a placebo or weekly doses of 200, 300, or 400 mg yogliptin, respectively. The primary efficacy end point in this analysis was hemoglobin A1c (HbA1c) change at 12 weeks relative to baseline. Relevant secondary outcomes were also examined, including fasting plasma glucose (FPG), 2 h-postprandial plasma glucose (PPG), body weight, and the rate of individuals who achieved the treatment goal of HbA1c ≤ 7% at 12 weeks from baseline. RESULTS: A total of 81 cases who received either the placebo (20 cases) or 200 (20 cases), 300 (20 cases), or 400 (21 cases) mg yogliptin were examined in the full analysis set. At 12 weeks, changes in HbA1c levels from baseline were 0.17 (-0.22, 0.57) in the placebo group, and -0.75 (-1.15, -0.35), -0.52 (-0.93, -0.11) and -1.02 (-1.41, -0.64) (mean % [95% confidence interval], p < .001 vs. placebo) in the 200, 300, and 400 mg yogliptin groups, respectively. From week four, significant improvements in secondary efficacy outcomes among patients administered the yogliptin monotherapy were observed. FPG showed markedly more pronounced reduction after treatment with yogliptin at 200, 300, and 400 mg in comparison with placebo patients at 4, 8, and 12 weeks. At 12 weeks, goal attainment (HbA1c ≤ 7%) was reached in 0%, 20.00%, 15.80%, and 33.33% of the placebo and three Yogliptin dosage groups, respectively. Adverse events were comparable in all groups. CONCLUSIONS: This study demonstrated that yogliptin controlled glycemia in Chinese T2DM cases, with a great safety profile. The current findings supported that any of the three doses of yogliptin, administered once a week, could be used for phase III clinical studies.

Pharmacokinetics and Pharmacodynamics of Henagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, in Chinese Patients with Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVE: Henagliflozin, a selective inhibitor of the renal sodium glucose cotransporter-2, was developed for type 2 diabetes mellitus (T2DM). This study characterized single- and multiple-dose pharmacokinetics and pharmacodynamics of henagliflozin in Chinese patients with T2DM. METHODS: Thirty T2DM patients were randomized in a 4:1 ratio to orally receive either henagliflozin 5, 10, 20 mg/day or placebo for 10 days, except on day 2 and day 3. Pharmacokinetic and pharmacodynamic profiles were measured on day 1 and day 10. RESULTS: Henagliflozin exhibited dose-proportional plasma concentrations with a half-life ranging from 9.1 to 14 h. Steady-state plasma henagliflozin concentration was reached by day 7 in all active treatment groups. Henagliflozin decreased the 24-h mean plasma glucose by -0.3, -1.0 and -1.0 mmol/L with doses of 5, 10 and 20 mg on day 1, respectively. The corresponding values on day 10 were -0.8, -0.9 and -1.2 mmol/L. Twenty-four-hour urinary glucose excretion increased by 11, 65 and 82 times with doses of 5, 10 and 20 mg on day 1, respectively, with a similar trend on day 10. No treatment-related serious adverse events or discontinuations due to adverse events occurred. CONCLUSIONS: The observed pharmacokinetic and pharmacodynamic profiles of henagliflozin support a once-daily dosing regimen in Chinese T2DM patients.

Epidemiology of CTX-M-type extended-spectrum beta-lactamase (ESBL)-producing nosocomial -Escherichia coli infection in China.

BACKGROUND: Escherichia coli is one of the most common clinical pathogens causing nosocomial infection. The widespread cefotaxime-beta lactamases (CTX) has increased the multidrug resistance (MDR) of E. coli and has brought great trouble to the doctor treating the infection. METHODS: ESBL-positive E. coli isolates were collected from different hospitals in different areas and the minimal inhibitory concentration (MIC) was analyzed by the agar dilution method. The resistance gene types were detected using polymerase chain reaction (PCR) and the sequence types were determined by multilocus sequence typing (MLST). RESULTS: We found that the blaCTX-M-1 group and the blaCTX-M-9 group were the main CTX-M gene types, with many kinds of MLST gene types. Except for TEM with high isolate, SHV, OXA and VEB were relatively rare, while no PER and GES was detected. Most strains may have other resistance mechanisms, and the ESBL positive strains have high resistance not only to cephalosporins but also to other kinds of antibiotics. CONCLUSION: The study provides wide epidemiological data and enables more effective infection control and treatment plans.

Opposite effects of cefoperazone and ceftazidime on S­ribosylhomocysteine lyase/autoinducer-2 quorum sensing and biofilm formation by an Escherichia coli clinical isolate.

To investigate the effects of subminimum inhibitory concentrations of cephalosporins on bacterial biofilm formation, the biofilm production of 52 Escherichia (E.) coli strains was examined following treatment with cephalosporin compounds at 1/4 minimum inhibitory concentrations (MICs). Ceftazidime (CAZ) inhibited biofilm formation in seven isolates, while cefoperazone (CFP) enhanced biofilm formation in 18 isolates. Biofilm formation of E. coli E42 was inhibited by CAZ and induced by CFP. Therefore, using reverse transcription­polymerase chain reaction, the expression of the biofilm­modulating genes of this isolate was investigated. To monitor the production of the autoinducer of quorum sensing in E. coli, autoinducer­2 (AI­2) production was detected by measuring the bioluminescence response of Vibrio harveyi BB170. Antisense oligonucleotides (AS­ODNs) targeting S­ribosylhomocysteine lyase (luxS) inhibited the expression of the luxS gene in E. coli. CAZ at 1/4 MIC reduced luxS mRNA levels and the production of AI­2, whereas CFP at 1/4 MIC had the opposite effect. AS­ODNs targeting luxS significantly decreased the aforementioned inhibitory effects of CAZ and the induction effects of CFP on E. coli biofilm formation. Therefore, biofilm formation by the E. coli clinical isolate E42 was evoked by CFP but attenuated by CAZ at sub­MICs, via a luxS/AI­2­based quorum sensing system.

Potent in vitro synergism of fusidic acid (FA) and berberine chloride (BBR) against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

It was found in the present study that combined use of fusidic acid (FA) and berberine chloride (BBR) offered an in vitro synergistic action against 7 of the 30 clinical methicillin-resistant Staphylococcus aureus (MRSA) strains, with a fractional inhibitory concentration (FIC) index ranging from 0.5 to 0.19. This synergistic effect was most pronounced on MRSA 4806, an FA-resistant isolate, with a minimum inhibitory concentration (MIC) value of 1,024 µg/ml. The time-kill curve experiment showed that FA plus BBR yielded a 4.2 log10 c.f.u./ml reduction in the number of MRSA 4806 bacteria after 24-h incubation as compared with BBR alone. Viable count analysis showed that FA plus BBR produced a 3.0 log10 c.f.u./ml decrease in biofilm formation and a 1.5 log10 c.f.u./ml decrease in mature biofilm in viable cell density as compared with BBR alone. In addition, phase contrast micrographs confirmed that biofilm formation was significantly inhibited and mature biofilm was obviously destructed when FA was used in combination with BBR. These results provide evidence that combined use of FA and BBR may prove to be a promising clinical therapeutic strategy against MRSA.