Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the inactivated vaccine BBIBP-CorV. Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the "immune-escape" Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.

Cytotoxic diaporindene and tenellone derivatives from the fungus Phomopsis lithocarpus / 中国天然药物

Nine new compounds, including five natural rarely-occurring 2, 3-dihydro-1H-indene derivatives named diaporindenes E-I (1-5), and four new benzophenone analogues named tenellones J-M (6-9) were isolated from the deep-sea sediment-derived fungus Phomopsis lithocarpus FS508. All the structures for these new compounds were fully characterized on the basis of spectroscopic data, NMR spectra, and ECD calculation and single-crystal X-ray diffraction analysis. The potential anti-tumor activities of compounds 1-9 against four tumor cell lines SF-268, MCF-7, HepG-2, and A549 were evaluated using the SRB method. Compound 7 exhibited cytotoxic activity against the SF-268 cell line with an IC

The Application of Performance Budget in Public Hospital Management / 中国卫生经济

Performance budgeting has been the direction of public budget reform in recent years.It is based on the performance,the target responsibility system,comprehensive budget management and performance evaluation of organic integration,broaden the management of new ideas.The application of performance budget in public hospital management has great significance to optimize the allocation of resources and improve management performance.

The Application of Performance Budget in Public Hospital Management / 中国卫生经济

Performance budgeting has been the direction of public budget reform in recent years.It is based on the performance,the target responsibility system,comprehensive budget management and performance evaluation of organic integration,broaden the management of new ideas.The application of performance budget in public hospital management has great significance to optimize the allocation of resources and improve management performance.

In vitro metabolic interconversion between baicalin and baicalein in the liver, kidney, intestine and bladder of rat / 药学学报

The present study is aimed to investigate the in vitro metabolic interconversion between baicalin (BG) and baicalein (B) in rat liver, kidney, intestine and bladder. BG and B were separately incubated with rat hepatic, renal, and intestinal microsomes, as well as bladder homogenates, for 30 min. The metabolites were identified and quantified by HPLC and metabolic kinetic parameters were obtained by fitting the data to the Michaelis-Menten equation. In hepatic microsomes, renal microsomes and bladder homogenates, but not in intestinal microsomes, BG was transformed into B, the hydrolysis metabolite of BG, with K(m) values being (44.65 +/- 6.01), (92.73 +/- 11.41), (74.60 +/- 3.68) micromol x L(-1), respectively, and V(max) values being (12.32 +/- 0.56), (3.30 +/- 0.18), (5.93 +/- 0.12) micromol x min(-1) x g(-1) (protein), respectively. In incubations with hepatic, renal, and intestinal microsomes and bladder homogenates, B was also transformed into BG, the glucuronidation metabolite of B, with K(m) values being (67.46 +/- 10.49), (226.7 +/- 71.59), (177.3 +/- 35.85), and (18.33 +/- 2.53) micromol x L(-1), respectively, and V(max) values being (14.74 +/- 0.97), (5.91 +/- 1.03), (38.14 +/- 3.60), and (1.22 +/- 0.05) micromol x min(-1) x g(-1) (protein), respectively. The results showed that the activity of UDP-glucuronosyltranferase (UGT) in intestinal microsomes was the highest among the four organs, and the activities of UGT were higher than that of glucuronidase (GUS) in hepatic, renal and intestinal microsomes, but the activity of GUS was higher than that of UGT in bladder homogenates.

Pharmacokinetics of flavonoids from xiexin decoction in rats / 药学学报

To study the pharmacokinetics of flavonoids from Xiexin decoction in rats. SD rats were given a single ig dose of Xiexin decoction 12 g x kg(-1), plasma and urine were collected before and after dosing. Flavonoids components in plasma and urine were measured by HPLC. Pharmacokinetic parameters were determined from the plasma concentration-time data and urinary excretion-time data with the DAS software package. Baicalin was incubated with the rat renal homogenate to investigate its metabolism in vitro. After oral administration of Xiexin decoction baicalin and wogonoside were quickly absorbed and exhibited double peak phenomena in their plasma concentrations. The first peaks in plasma concentrations of baicalin and wogonoside reached Cmax1 of (10 +/- 8) and (1.5 +/- 0.5) mg x L(-1) at Tmax1 of (0.27 +/- 0.09) and (0.17 +/- 0.00) h, while the second peaks reached Cmax2 of (3. 9 0. 5) and (0. 74 +/- 0.11) mg x L(-1) at Tmax2 of (7.6 +/- 2.6) and (16.0 +/- 0.0) h, respectively. The T(1/2) of baicalin and wogonoside were (7 +/- 3) and (6.4 +/- 2.1) h, AUC(0-infinity) were (57 +/- 12) and (15 +/- 3) mg x h x L(-1), respectively. After oral administration of Xiexin decoction, not only baicalin and wogonoside but also baicalein and wogonin can be detected in the urine. The amounts of baicalin, wogonoside, baicalein and wogonin excreted from urine during 0-72 h were (1.4 +/- 0.3), (3.4 +/- 1.3), (2.2 +/- 0.97), (10 +/- 4)% of dose given in rats, respectively. The excretion T(1/2) of the four flavonoids were (6.9 +/- 2.1), (9 +/- 4) , (8.2 +/- 2.0) and (7.2 +/- 1.8) h, respectively. Baicalin was metabolized into baicalein in the rat renal homogenate in vitro, and the kinetic parameters were measured as Vmax = 702 nmol x min(-1) x g(-1) (protein) and Km=135 micromol x L(-1). After oral administration of Xiexin decoction, flavonoids can be absorbed quickly. Only a small quantity of baicalin, wogonoside, baicalein and wogonin were excreted from urine. Baicalin may be metabolized into baicalein in the rat kidney.

Agroinfiltration, a useful technique in plant molecular biology research / 生物工程学报

Agroinfiltration is a newly developed plant transient gene expression technique, which is simple, rapid and reproducible. It has been widely used in analyses of foreign gene expression, hypersensitive reaction, gene silencing, promoter activity and identification of new disease-resistance genes. In this paper, we describe the principle and the operation procedure of Agroinfiltration and its application in diverse aspects of plant molecular biology research. Our experiences in modification of the Agroinfiltration technique are also provided.

An Improved Simple and Quick Method for V-P and MR Tests / 微生物学通报

V-P and MR tests were done at the same time using white porcelain board.The results showed that the white porcelain method was simple and convenient compared to the traditional method.