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A safe, efficacious and deployable vaccine is urgently needed to control COVID-19 pandemic. We report here the preclinical development of a COVID-19 vaccine candidate, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and NHPs, and also elicited balanced TH1/TH2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25 g or 50 g ZF2001 prevented infection with SARS-CoV-2 in lung, trachea and bronchi, with milder lung lesions. No evidence of disease enhancement is observed in both models. ZF2001 is being evaluated in the ongoing international multi-center Phase 3 trials (NCT04646590) and has been approved for emergency use in Uzbekistan.
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BackgroundA safe and effective coronavirus disease 2019 (COVID-19) vaccine is urgently needed to control the ongoing pandemic. Although progress has been made recently with several candidates reporting positive efficacy results, COVID-19 vaccines developed so far cannot meet the global vaccine demand. We developed a protein subunit vaccine against COVID-19, using dimeric form of receptor-binding domain (RBD) as the antigen. We aimed to assess the safety and immunogenicity of this vaccine in humans and determine the appropriate dose and schedule for an efficacy study. MethodsWe did two randomized, double-blind, placebo-controlled, phase 1 and 2 trials for an RBD-based protein subunit vaccine, ZF2001. In phase 1 study, 50 healthy adults aged 18-59 years were enrolled and randomly allocated to three groups to receive three doses of vaccine (25 g or 50 g RBD-dimer, with adjuvant) or placebo (adjuvant-only) intramuscularly, 30 days apart. In phase 2 study, 900 healthy adults aged 18-59 years were enrolled and randomly allocated to six groups to receive vaccine (25 g or 50 g RBD-dimer, with adjuvant) or placebo (adjuvant-only) intramuscularly, with the former 3 groups given two doses and the latter 3 groups given three doses, 30 days apart. For phase 1 trial, the primary outcome was safety, as measured by the occurrence of adverse events and serious adverse events. The secondary outcome was immunogenicity as measured by the seroconversion rate and magnitude of antigen-binding antibodies, neutralizing antibodies and T-cell cytokine production. For phase 2 trial, the primary outcome included both safety and immunogenicity. These trials are registered with ClinicaTrials.gov, NCT04445194 and NCT04466085. FindingsBetween June 22 and September 15, 2020, 50 participants were enrolled to the phase 1 study (mean age 32.6 years) and 900 participants were enrolled to phase 2 study (mean age 43.5 years), to receive vaccine or placebo with a two-dose or three-dose schedule. For both trials, local and systemic adverse reactions were absent or mild in most participants. There were no serious adverse events related to vaccine in either trial. After three doses, neutralizing antibodies were detected in all participants receiving either 25 g or 50 g dose of vaccine in phase 1 study, and in 97% (the 25 g group) and 93% (the 50 g group) of participants, respectively, in phase 2 study. The SARS-CoV-2-neutralizing geometric mean titres (GMTs) were 94.5 for the 25 g group and 117.8 for the 50 g group in phase 1, and 102.5 for the 25 g group and 69.1 for the 50 g group in phase 2, exceeding the level of a panel of COVID-19 convalescent samples (GMT, 51). Vaccine induced balanced TH1 and TH2 responses. The 50 g group did not show enhanced immunogenicity compared with the 25 g group. InterpretationThe protein subunit vaccine ZF2001 is well-tolerated and immunogenic. The safety and immunogenicity data from phase 1 and 2 trials for ZF2001 support the use of 25 g vaccine dose with three-dose schedule to an ongoing phase 3 large-scale evaluation for safety and efficacy. FundingNational Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical.
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OBJECTIVE:To provide reference for standardizing the names of TCM from Rumex. METHODS:According to lit-erature research,the most frequently used names (such as Jinbuhuan,Tudahuang,Yangti) of TCM in Rumex were combed,and suggestions for existing problems were put forward. RESULTS & CONCLUSIONS:The TCM names were used confusedly,main-ly showing that inconsistent names of TCM from the same plant in different areas,same name of TCM from different plants in the same area,same name of TCM from different plants in different areas. The key to solving the confused use of names of TCM in Rumex is standardization and unification of medicinal plant source and names. It can be developed and solved in order by resource investigation and identification,establishing quality standard and excavating medicinal value,in which,conducting the resource in-vestigation and specie identification,determining the medicinal names,stipulating the official names and establishing the quality standard are the important work in future.
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Rhizoma Pinelliae Fermentata(RPF)wasoneofthecommonlyusedChinesemateriamedica(CMM). According to the ancient and modern literatures on RPF, the historical evolution, fermentation methods, chemical compositions, efficacy and microbes of RPF were systematically summarized in this paper. Through the analysis on existing problems of fermentation strains, effective components, quality standard and fermentation process, the corresponding solutions were proposed. This work may provide an idea and reference for the further study of RPF.
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This study was aimed to establish a rapid discrimination method of Pinellia ternataand its adulterants based on the odour fingerprints analysis.Typhonium flagelliforme and Arisaema Rhizome,which were the common adulterants of Pinellia ternata,were collected.The adulterants were mixed with Pinellia ternatain different proportions.E-nose technology was used to obtain the odour fingerprints of Pinellia ternataand its adulterants of different types and proportions.Chemometrics methods,such as the analysis of variance (ANOVA),principal component analysis (PCA) and discriminant factor analysis (DFA) were used in the analysis and discrimination on sensors response data collected by sensors.The results showed that there were obvious differences on the odour characteristics between Pinellia ternateand its adulterants.PCA can obviously discriminate Pinellia ternateand its adulterants.And the odour difference became obvious along with the increasing of the adulteration proportion.There was a linear relationship between e-nose signal and the proportion of Typhonium flagelliforme.The cumulative proportion in ANOVA of the DFA model was 100%.The correct recognition rate was not less than 97%.It was concluded that e-nose can be used for rapid discrimination of Pinellia ternataand its adulterants.This study provided new technology and method for the discrimination of adulterants of Chinese materia medica.
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Odor and taste are characteristic properties of traditional Chinese medicine (TCM). They are closely related to the chemical compositions in TCM. They are also the outer reflection of TCM quality and an important part of the character identification. This article reviewed the current research on odor and taste identification of TCM, which indicated that odor and taste identification had not been paid enough attention to and its research lagged behind modern social development. Based on current analytical techniques and methods, this article proposed a new idea for odor and taste identification of TCM. The idea emphasized the objectification of odor and taste and TCM identification research should be combined with chemical components analysis.
