ABSTRACT
The COVID-19 pandemic and the continued spreading of the SARS-CoV-2 variants have brought a grave public health consequence and severely devastated the global economy with recessions. Vaccination is considered as one of the most promising and efficient methods to end the COVID-19 pandemic and mitigate the disease conditions if infected. Although a few vaccines have been developed with an unprecedented speed, scientists around the world are continuing pursuing the best possible vaccines with innovations. Comparing to the expensive mRNA vaccines and attenuated/inactivated SARS-CoV-2 vaccines, recombinant protein vaccines have certain advantages, including their safety (non-virus components), potential stronger immunogenicity, broader protection, ease of scaling-up production, reduced cost, etc. In this study, we reported a novel COVID-19 vaccine generated with RBD-HR1/HR2 hexamer that was creatively fused with the RBD domain and heptad repeat 1 (HR1) or heptad repeat 2 (HR2) to form a dumbbell-shaped hexamer to target the spike S1 subunit. The novel hexamer COVID-19 vaccine induced high titers of neutralizing antibody in mouse studies (>100,000), and further experiments also showed that the vaccine also induced an alternative antibody to the HR1 region, which probably alleviated the drop of immunogenicity from the frequent mutations of SARS-CoV-2.
ABSTRACT
OBJECTIVE： To observe the efficacy and safety of Bufei huoxue capsules combined with Azithromycin tablets in the treatment of patients with stable COPD. METHODS： Totally 140 patients with stable COPD were collected from Anhui Chest Hospital during Jun. 2014-Feb. 2018， and then divided into control group and observation group according to random number table， with 70 cases in each group. Both groups received smoking cessation intervention and symptomatic treatment. Control group was additionally given Tiotropium bromide powder for inhalation， once a day+Azithromycin tablets 0.25 g， twice a week. Observation group were additionally given Bufei huoxue capsules 4 pills， 3 times a day， on the basis of control group. Both groups were treated for 180 d continuously. The clinical efficacies of 2 groups were observed， and the levels of serum inflammatory factors （CRP， IL-6 and TNF-α）， lung function related indexes （PEF， FEV1 and FEV1/FVC） and COPD related symptoms （time of AECOPD attack and 6MWT） were observed before and after treatment. The occurrence of ADR was recorded. RESULTS： Totally 9 cases withdrew from the study in control group， and 3 cases in observation group. A total of 128 cases （61 cases in control group， 67 cases in observation group） completed the study. Total response rate was 92.54％ in observation group， which was significantly higher than 80.33％ in control group（P＜0.05）. Before treatment， there was no statistical significance in the levels of serum inflammatory factors， lung function related indexes or COPD related symptoms （P＞0.05）. After treatment， the levels of CRP， IL-6 and TNF-α in 2 groups were decreased significantly， and the times of AECOPD attack were decreased significantly； observation group was significantly lower or less than control group. PEF， FEV1 and FEV1/FVC were increased significantly in 2 groups and 6MWT was prolonged significantly； observation group was significantly higher or longer than control group （P＜0.05）. One case suffered from skin rash in control group， and two cases had mild nausea in observation group； no severe ADR was found in both groups. CONCLUSIONS： Bufei huoxue capsules combined with Azithromycin tablets can significantly reduce the level of serum inflammatory factors of stable COPD patients， improve their lung function， and relieve clinical symptoms with good safety.
ABSTRACT
The present work describes a series of human growth hormone (hGH) albumin binder conjugates with an extended in vivo half-life. A broad range of different conjugates were studied by varying the albumin binder structure and conjugation site. Conjugates were conveniently obtained by reductive alkylation or by alkylation to introduced cysteines using functionalized albumin-binding side chains. In vitro and in vivo profiling provided the basis for identification of position L101C in human growth hormone as the most optimal position for conjugation, where both a sufficient level of receptor binding and a suitably long half-life could yield a molecule with potential for a once-weekly dosing regimen.
