An in-depth investigation of the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine

BACKGROUNDIn-depth investigations of the safety and immunogenicity of inactivated SARS-CoV-2 vaccines are needed. METHODIn a phase I randomized, double-blinded, and placebo-controlled trial involving 192 healthy adults 18-59 years of age, two injections of three different doses (50 EU, 100 EU and 150 EU) of an inactivated SARS-CoV-2 vaccine or the placebo were administered intramuscularly with a 2- or 4-week interval between the injections. The safety and immunogenicity of the vaccine were evaluated within 28 days. FINDINGIn this study, 191 subjects assigned to three doses groups or the placebo group completed the 28-day trial. There were 44 adverse reactions within the 28 days, most commonly mild pain and redness at the injection site or slight fatigue, and no abnormal variations were observed in 48 cytokines in the serum samples of immunized subjects. The serum samples diluted from 1:32 to 1:4096 and incubated with the virus did not show antibody-dependent enhancement effects (ADEs) with regard to human natural killer cells, macrophages or dendritic cells. At day 14, the seroconversion rates had reached 92%, 100% and 96% with geometric mean titers (GMTs) of 18.0, 54.5 and 37.1, and at day 28, the seroconversion rates had reached 80%, 96% and 92% with GMTs of 10.6, 15.4 and 19.6in 0, 14 and 0, 28 procedures, respectively. Seroconversion was associated with the synchronous upregulation of ELISA antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. Transcriptome analysis shaped the genetic diversity of immune response induced by the vaccine. INTERPRETATIONIn a population aged 18-59 years, this inactivated SARS-CoV-2 vaccine was safe and immunogenic. Trial registrationNCT04412538 FUNDINGThe National Key R&D Program of China (2020YFC0849700), the Program of Chinese Academy of Medicine Science and the Major Science and Technology Special Projects of Yunnan Province.

Advances in the effectiveness of rotavirus vaccines and its influencing factors / 中华微生物学和免疫学杂志

Rotavirus is the leading cause of acute gastroenteritis in children, and vaccines are the most effective measure to control rotavirus diarrhea. Currently, two vaccines, namely Rotarix and RotaTeq, are widely used worldwide. In addition, several vaccines are licensed in some countries. This review summa-rized the effectiveness of licensed rotavirus vaccines and the potential factors which might affect the effective-ness of these vaccines. In addition, progress in novel vaccine candidates in development was also included in this review.

COE inhibits vasculogenic mimicry in hepatocellular carcinoma via suppressing Notch1 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Vasculogenic mimicry (VM) has been suggested to be present in various malignant tumors and associated with tumor nutrition supply and metastasis, leading to poor prognosis of patients. Notch1 has been demonstrated to contribute to VM formation in hepathocellular carcinoma (HCC). Celastrus orbiculatus extract (COE), a mixture of 11 terpenoids isolated from the Chinese Herb Celastrus orbiculatus Vine, has been suggested to be effective in cancer treatment. AIM OF THE STUDY: In the current study, experiments were carried out to examine the effect of COE on VM formation and HCC tumor growth both in vitro and in vivo. MATERIALS AND METHODS: CCK-8 assay and Nikon live-work station were used to observe the viability of malignant cells treated with COE. Cell invasion was examined using Transwell. Matrigel was used to establish a 3-D culture condition for VM formation. Changes of mRNA and protein expression were examined by RT-PCR and Western Blot respectively. Tumor growth in vivo was monitored using in vivo fluorescence imaging device. PAS-CD34 dual staining and electron microscopy were used to observe VM formation. Immunohistochemical staining (IHC) was used to examine Notch1 and Hes1 expression in tumor tissues. RESULTS: Results showed that COE can inhibit HCC cells proliferation and invasion in a concentration-dependent manner. VM formation induced by TGF-ß1 was blocked by COE. In mouse xenograft model, COE inhibited tumor growth and VM formation. Both in vitro and in vivo studies showed that COE can downregulate expression of Notch1 and Hes1. CONCLUSION: The current results indicate that COE can inhibit VM formation and HCC tumor growth by downregulating Notch1 signaling. This study demonstrates that COE is superior to other anti-angiogenesis agents and can be considered as a promising candidate in HCC treatment.

Era of vaccination heralds a decline in incidence of hepatitis A in high-risk groups in China.

BACKGROUND: Hepatitis A was ranked first among all of the different types of viral hepatitis in China, which occurred an average of 500,000 cases annually during the 1980's. A live attenuated hepatitis A vaccine was applied in preventing of the disease in 1992, large scale used in vaccination program in 1995, and incorporated in the Expanded Program of Immunization in 2008 in China. OBJECTIVE: The objective of this study was to determine whether, and to what extent, the decline in the incidence of hepatitis A in China was the result of hepatitis A (HA) vaccination. MATERIALS AND METHODS: Official documents and longitudinal serological follow-up studies were reviewed to compare the incidence of HA before and after the introduction of the vaccine. RESULTS: National trends in the incidence of HA in China saw rates decrease by 92.7% in 2009, compared to the levels seen in 1992. A mass vaccination program was carried out in 3-18 year old children (Wuhan City, China), and its protective efficacy was 85.4%. In a mass vaccination program of an entire population (Shenshi County, China), the annual HA incidence decreased from 359.7/100,000 to 17.7/100,000 (almost 20.3 times). There was a significant relationship found between vaccine coverage and the incidence of HA, the correlation of the negative regression was significant at the 1% (Kendall rank correlation, significant level P < 0.05). CONCLUSIONS: In summary, this study highlights the important role of implementing a vaccination program in decreasing the incidence of HA, and the large protective efficacy of such a strategy, as demonstrated in China.

Progress of miRNAs in lung cancer / 国际肿瘤学杂志

Micro RNA has been revealed to be involved in a series of essential biological processing including cell development, proliferation, differentiation and apoptosis. Micro RNA functions as tumor suppressor or tumor promoter, which might be used to measure lung cancer cell amount and to serve as markers of diagnosis and prognosis of lung cancer.

Mutations in the gyrA and parC genes of quinolone-resistant Shigella flexneri clinical isolates / 中华传染病杂志

Objective To identify the mutations of DNA gyrase gyrA and Topoisomerase Ⅳ parC genes in quinolone-resistant Shigella flexneri clinical isolates and evaluate the relevance of amino acid changes in GyrA and ParC to quinolone resistance. Methods Based on the antimicrobial susceptibility testing, 47 S.flexneri clinical isolates with different quinolone susceptibility were selected and the fragments including the quinolone resistance-determining region (QRDR) in gyrA and parC were PCR amplified and sequenced. SAS (V 8.2) software was used to analyze the correlation between quinolone resistance and changes in GyrA and ParC. Results Sense mutation(s) in gyrA and parC were commonly observed in all of 44 quinolone-resistant isolates, whereas no sense mutation was found in the 3 quinolone-susceptible ones. The most frequent mutation is at codon 83(TCG→TTG) of gyrA, which was observed in 43 quinolone-resistant isolates. The mixed model analysis indicated that the alterations in amino acid 83 of GyrA and amino acid 80 of ParC are close related to nalidixic acid resistance (P

Expression of Mage-A1、A2、A3 in breast cancer tissue and breast cancer cell lines / 中国普通外科杂志

Objective To study the expression of Mage A1、A2、A3 in breast cancer tissues and four breast cancer cell lines Methods The expression of Mage A1、A2、A3 in breast cancer tissues and four breast cancer cell lines, MCF 7、Sk Br 3、MDA MB 435s and TM40D was detected by reverse transcription polymerase chain reaction (RT PCR) Results The positive expression rate of Mage A in breast cancer tissues was 13/33 (39%), of Mage A1 was 4/33 (12%), of Mage A2 was 8/33 (24%), and of Mage A3 was 7/33 (21%), respectively Both Mage A1 and Mage A3 were positive in breast cancer cell line MCF 7 and Sk Br 3 MDA MB 435s expressed Mage A2 and Mage A3 Mage A3 was positive in TM40D Conclusion Mage genes were often expressed in breast cancer, but expression of Mages varies in the breast cancer cell lines Mage genes encoding proteins are eligible for Mage peptide based active immunotherapy

PGE_2 promotes the migratory ability and immunological effect of bone marrow-derived dendritic cells loaded with breast carcinoma antigen / 中国普通外科杂志

Objective To promote the migratory ability and immunological effect of bone marrow-derived dendritic cells ( BMDC) loaded with breast carcinoma antigen. Methods DCs were cultured by the medium containing rmGM-CSF and rmIL-4. After loaded with breast carcinoma antigen, DCs were stimulated with PGE2 for 1day. CD86, CD80, and CCR7 were measured by flow cytometry. The expression of CCR7 on surface of BMDC was also detected by RT-PCR and Western blotting. The chemotaxis assay was measured by migration through a polycarbonate filter in transwell chambers. The competence of inducing mixed lymphocyte response (MLR) and specific cytotoxic T lymphocyte ( CTL) were detected with MTT. The effect of DC blocking tumor growth in breast carcinoma model were also studied. Results Compared with control group, PGE2 upregulated surface markers of CD86, CD80, and CCR7 (P