Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials / 中华医学杂志(英文版)

BACKGROUND@#The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.@*METHODS@#Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.@*RESULTS@#In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.@*CONCLUSIONS@#Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).

A new disubstituted succinate from the roots of Tagetes erecta / 药学学报

Nine compounds were isolated from 95% ethanol extract of the roots of Tagates erecta by silica gel column chromatography and Sephadex LH-20 chromatography. Their structures were identified by spectroscopic data as 5-hydroxymethylfurfuryl methyl succinate (1), 5,7,3'-trihydroxyl-3,6,4'-trimethoxylflavone (2), syringic acid (3), 5,7,4'-trihydroxyl-3,6-trimethoxylflavone (4), patuletin-4'-methoxyl-7-O-β-D-glucopyranoside (5), patulitrin (6), 5,3'-dihydroxyl-3,6,4'-trimethoxylflavone-7-O-β-D-glucopyranoside (7), (2,2'-biththiophen)-5-ol (8), and 3-hydroxyl-4-methoxyl benzoic acid (9). Among them, compound 1 is a new disubstituted succinate and compound 8 was isolated from a natural resource for the first time. Compounds 2, 4, 5 and 9 were isolated from this genus for the first time. By measuring the biological activity and virulence of different compounds against soybean cyst nematode, it has found that compounds 1-8 exhibited a toxic effect on soybean cyst nematode, and ED50 values indicate that compounds 3 and 7 are the most potent, with ED50 values of 0.008 μg·mL-1.

Risk management of medical equipment clinical trial / 医疗卫生装备

Objective To propose a set of management methods for minimized risk and continuous improvement of medical equipment clinical trial.Methods The problems were summarized on pre-trial preparation,design and signing of informed consent,insurance-related issues,supervision and quality control,perception of adverse events,and then some countermeas-ures were put forward accordingly.Results A risk management system was established for medical equipment clinical trial whole-course management.Conclusion Planning,recognition and evaluation have to be implemented over all the links of medical equipment clinical trial risk management,and corresponding countermeasures should be carried out for minimized risk and continuous improvement.

Protective effect of DNA vaccine with the gene encoding 55kDa antigen fragment against Pneumocystis carinii in mice

OBJECTIVE@#To evaluate the protective effect of DNA vaccine with the gene encoding 55kDa antigen fragment of Pneumocystis carinii (P. carinii) against P. carinii in mice.@*METHODS@#The fragment of the antigen within p55(p55-582) was cloned. Then recombinant plasmid was constructed based on the eukaryotic expression vector pcDNA3.1(+). BALB/c mice were used as experimental models to examine the immunogenicity of pcDNA3.1(+)-p55-582. ELISA and RT-PCR were used to evaluate the role of this kind of DNA vaccine.@*RESULTS@#The results of western blot indicated that the recombinant DNA[pcDNA3.1(+)-p55-582] could be expressed correctly and had antigenicity in transfected COS-7 cells. ELISA and RT-PCR showed that pcDNA3.1(+)-p55-582 elicited antibody production, stimulated lymphocyte proliferation and provided partial protection by reducing the P. carinii burden.@*CONCLUSIONS@#The data demonstrate that pcDNA3.1(+)-p55-582 might be potent vaccination that can afford the partial protection for the immunized animals.

Surgical treatment of corneal complications in patients with ocular cicatriciai pemphigoid / 眼科

Objective To observe the outcome of patients with ocular cicatricial pemphigoid (OCP) after amniotic membrane grafting or penetrating keratoplasty.Design Retrospective,noncomparative case series.Participants 3 consecutive OCP patients (4 eyes),were included.Methods For 3 patients (4 eyes) in this study,preoperative visual acuity was from HM/5 cm to HM/10 cm.The symblepharon (gradeⅢ) of 2 patients (3 eyes) were detached and amniotic membrane was transplanted,and bandage contact lens were used till 2 months after operations.The other patient (1 eye) was undergone penetrating keratoplasty with glycerol-cryopreserved cornea because of corneal ulcer and perforation.Main Outcome Measures Visual acuity,recovering of conjunctiva and cornea.Results Am- niotic membrane dissolved about 1 month after operation in 2 patients (3 eyes).Symblepharon changed from gradeⅢto gradeⅡ,visual acuity increased to 0.04-0.05,central corneal epithelium was regenerated significantly,and a little new vessel appeared at corneal lim- bus in 2 patients (2 eyes).The graft deliquesced in the patient with penetrating keratoplasty at 20 days after operation and undergone penetrating keratoplasty again after 1 month.In this patient,the graft molten induced the ocular contents run-off and became eyeball at- rophy eventually.Conclusion Our small sample study shows that the symblepharon detachment and amniotic membrane transplantation is effective for improving visual acuity in OCP with ocular surface dysfunction.However,because of various factors,penetrating kerato- plasty is ineffective for OCP with perforating corneal ulcer.

Preparation and permeation studies of soybean lecithin-based vesicles / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate various methods for constructing soybean lecithin (SL)-based vesicles and evaluate the permeation-enhancing effect of SL-based vesicles on the penetration of insulin through buccal mucosa.</p><p><b>METHODS</b>The ultrasonic method, high speed shear method and high pressure homogenization method were respectively used to prepare the SL-based vesicles, and the particle size of the vesicles was measured with photon correlation spectrometry (PCS). The penetration rate of insulin through porcine buccal mucosa was investigated with the Valia-Chien diffusion cells.</p><p><b>RESULTS</b>The average particle sizes of 3 formulations of SL-based vesicles were 97.39, 85.60, and 100.60 nm when prepared by ultrasonic method, and were 58.7, 88.7, and 91.9 nm when prepared by high pressure homogenization method. Both vesicles presented good stability. However, the SL-based vesicles prepared by high speed shear method had larger average diameters and were found to be unstable. Transmission electron microscopy showed that SL-based vesicles had a spherical shape and the result accorded with PCS. The permeation flux of insulin of formulation 1 and control solution were 0.0024 and 0.0008 IU x ml(-1) x min(-1), respectively. The accumulative amount of formulation 1 at 180 min was (0.436 +/- 0.010 ) IU x ml(-1), which was 1.46 times higher than the control solution.</p><p><b>CONCLUSIONS</b>The SL-based vesicles obtained using high pressure homogenization method are characterized by small particle size, narrow distribution, good stability, and powerful permeation-enhancing effect, which enables them to be good carriers for the buccal delivery of insulin.</p>