Safety and immunogenicity of a mosaic vaccine booster against Omicron and other SARS-CoV-2 variants: a randomized phase 2 trial.

An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to 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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline 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 by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2.

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

[Studies on chemical constituents from stem barks of Fraxinus paxiana].

OBJECTIVE: To investigate the chemical constituents of Fraxinus paxiana. METHOD: The chemical constituents were isolated and purified by chromatographic techniques and the structures of the compounds were identified with or by spectroscopic methods. RESULT: Fifteen compounds were obtained from the methanol extract of F. paxiana and their structures were elucidated as esculin (1), esculetin (2), fraxin (3), fraxetin (4), salidroside (5), osmanthuside H (6), liriodendrin (7), 3-(4-beta-D-glucopyranosyloxy-3-methoxy)-phenyl-2E-propenol (8), threo-syringylglycerol (9), euscaphic acid (10), 3-hydroxy-1-(4-hydroxy-3, 5-dimethoxyphenyl)-1-propanone (11), omega-hydroxypropioguaiacone (12), sinapyladehyde (13), betulinic acid (14) and mannitol (15). CONCLUSION: All compounds were obtained from this plant for the first time.

[Effects of different types and standard of processing vinegaron inherent constituents in rhizoma of Corydalis yanhusuo].

OBJECTIVE: To investigate the effects of processing adjuvants-different types of processing vinegar on effective constituents in rhizoma of Corydalis yanhusuo, and evaluate the quality of different types of vinegar in China. METHOD: The HPLC method was adopted to determine the extraction solubility of dl-tetrahydropalmation and total alkaloids in rhizoma of Corydalis yanhusuo processed by vinegar. The sample extracts were separated on kromasil ODS column with mobile phase of methanol-1% phosphoric acid solution(65:35) and detection wavelength was 280 nm. RESULT: There was a remarkable increase in extraction solubility of dl-tetrahydropalmation and total alkaloids in the rhizoma of Corydalis yanhusuo processed by the vinegar products with high content of total acids or with known trademarks. CONCLUSION: Some types of vinegar with known trademarks had been preliminarily selected for the process of Chinese traditional medicine and they also met the requitrement of processing adjuvants with medicine grade. The results will be benefited to the foundation of standardization of vinegar.

[Determination of synephrine and N-methyltyramine in Pericarpium Citri Reticulatae viride by HPLC].

OBJECTIVE: To establish a quantitative method for determination of synephrine and N-methyltyramine in Citri Reticulatae. METHOD: Samples were extracted with 30% methanol. ODS column was used with methanol-water-sodium dodecyl sulfate (55:45:0.1) as mobile phase. Detection wavelength was 285 nm. RESULT: Synephrine and N-methyltyramine in sample solution were well separated. Linearity of synephrine was good (r = 0.9999) in range of 0.35-11.24 microg. The average recovery was 97.1%, and RSD of repeatability was 1.9%. CONCLUSION: This method can be used for quality control of Citri Reticulatae.