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BackgroundInformation on the safety and immunogenicity of the omicron BA.4/BA.5-containing bivalent booster mRNA-1273.222 are needed. MethodsIn this ongoing, phase 2/3 trial, 50-g mRNA-1273.222 (25-g each ancestral Wuhan-Hu-1 and omicron BA.4/BA.5 spike mRNAs) is compared to 50-g mRNA-1273, administered as second boosters in adults who previously received a 2-injection (100-g) primary series and first booster (50-g) dose of mRNA-1273. The primary objectives were safety and immunogenicity 28 days post-boost. ResultsParticipants received 50-g of mRNA-1273 (n=376) or mRNA-1273.222 (n=511) as second booster doses. Omicron BA.4/BA.5 and ancestral SARS-CoV-2 D614G neutralizing antibody geometric mean titers (GMTs [95% confidence interval]) after mRNA-1273.222 (2324.6 [1921.2-2812.7] and 7322.4 [6386.2-8395.7]) were significantly higher than mRNA-1273 (488.5 [427.4-558.4] and 5651.4 (5055.7-6317.3) respectively, at day 29 post-boost in participants with no prior SARS-CoV-2-infection. A randomly selected subgroup (N=60) of participants in the mRNA-1273.222 group also exhibited cross-neutralization against the emerging omicron variants BQ.1.1 and XBB.1. No new safety concerns were identified with mRNA-1273.222. Vaccine effectiveness was not assessed in this study; in an exploratory analysis 1.6% (8/511) of mRNA-1273.222 recipients had Covid-19 post-boost. ConclusionThe bivalent omicron BA.4/BA.5-containing vaccine mRNA-1273.222 elicited superior neutralizing antibody responses against BA.4/BA.5 compared to mRNA-1273, with no safety concerns identified. (Supported by Moderna; ClinicalTrials.gov Identifier: NCT04927065)
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During the SARS-CoV-2 pandemic, multiple variants with differing amounts of escape from pre-existing immunity have emerged, causing concerns about continued protection. Here, we use antigenic cartography to quantify and visualize the antigenic relationships among 16 SARS-CoV-2 variants titrated against serum samples taken post-vaccination and post-infection with seven different variants. We find major antigenic differences caused by substitutions at spike positions 417, 452, 484, and possibly 501. B.1.1.529 (Omicron BA.1) showed the highest escape from all sera tested. Visualization of serological responses as antibody landscapes shows how reactivity clusters in different regions of antigenic space. We find changes in immunodominance of different spike regions depending on the variant an individual was exposed to, with implications for variant risk assessment and vaccine strain selection. One sentence summaryAntigenic Cartography of SARS-CoV-2 variants reveals amino acid substitutions governing immune escape and immunodominance patterns.
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Objective:To investigate the prevalence of anxiety and depression in patients undergoing thoracic tumor radiotherapy, preliminarily evaluate the nutritional risk of patients, and analyze the possible influential factors of anxiety and depression and their correlation with nutritional risk, providing a theoretical basis for further formulating a personalized psychological nursing plan for patients undergoing thoracic tumor radiotherapy.Methods:A total of 121 patients who underwent thoracic tumor radiotherapy between April 2019 and March 2020 in Cancer Hospital of The University of Chinese Academy of Sciences were selected for this study. We evaluated patients' psychological statuses using the Hospital Anxiety and Depression Scale and patients' nutritional risk using the Nutrition Risk Screening. We performed univariate analysis, unconditional logistic regression analysis, and contingency analysis to analyze the factors that affected the psychological status of patients undergoing thoracic tumor radiotherapy and correlate patients' psychological status with nutritional risk.Results:Among 121 patients, 99 (81.8%) patients undergoing thoracic tumor radiotherapy would develop or had developed anxiety, and 42 (34.7%) patients were at the boundary of depression or had depression. Correlation analysis revealed that nutritional risk was correlated with the prevalence of anxiety and depression. Logistic regression analysis showed that surgery, first radiotherapy, and nutritional risk were the factors that affected the prevalence of anxiety. Marital status, location of tumors, surgery, first radiotherapy, and nutritional risk affected the prevalence of depression.Conclusion:Patients undergoing thoracic tumor radiotherapy have serious psychological problems. Nutritional risk is positively correlated with the prevalence of anxiety and depression. Surgery and first radiotherapy are the factors that affect the prevalence of anxiety and depression.
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The Omicron variant of SARS-CoV-2 is raising concerns because of its increased transmissibility and potential for reduced susceptibility to antibody neutralization. To assess the potential risk of this variant to existing vaccines, serum samples from mRNA-1273 vaccine recipients were tested for neutralizing activity against Omicron and compared to neutralization titers against D614G and Beta in live virus and pseudovirus assays. Omicron was 41-84-fold less sensitive to neutralization than D614G and 5.3-7.4-fold less sensitive than Beta when assayed with serum samples obtained 4 weeks after 2 standard inoculations with 100 {micro}g mRNA-1273. A 50 {micro}g boost increased Omicron neutralization titers and may substantially reduce the risk of symptomatic vaccine breakthrough infections.
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SARS-CoV in 2003, SARS-CoV-2 in 2019, and SARS-CoV-2 variants of concern (VOC) can cause deadly infections, underlining the importance of developing broadly effective countermeasures against Group 2B Sarbecoviruses, which could be key in the rapid prevention and mitigation of future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV, bat CoVs WIV-1 and RsSHC014, and SARS-CoV-2 variants D614G, B.1.1.7, B.1.429, B1.351 by a receptor-binding domain (RBD)-specific antibody DH1047. Prophylactic and therapeutic treatment with DH1047 demonstrated protection against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B1.351infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among Sarbecoviruses. We conclude that DH1047 is a broadly neutralizing and protective antibody that can prevent infection and mitigate outbreaks caused by SARS-like strains and SARS-CoV-2 variants. Our results argue that the RBD conserved epitope bound by DH1047 is a rational target for pan Group 2B coronavirus vaccines.
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The development of a portfolio of SARS-CoV-2 vaccines to vaccinate the global population remains an urgent public health imperative. Here, we demonstrate the capacity of a subunit vaccine under clinical development, comprising the SARS-CoV-2 Spike protein receptor binding domain displayed on a two-component protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human primates. We evaluated five different adjuvants combined with RBD-NP including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an alpha-tocopherol-containing squalene-based oil-in-water emulsion used in pandemic influenza vaccines; AS37, a TLR-7 agonist adsorbed to Alum; CpG 1018-Alum (CpG-Alum), a TLR-9 agonist formulated in Alum; or Alum, the most widely used adjuvant. All five adjuvants induced substantial nAb and CD4 T cell responses after two consecutive immunizations. Durable nAb responses were evaluated for RBD-NP/AS03 immunization and the live-virus nAb response was durably maintained up to 154 days post-vaccination. AS03, CpG-Alum, AS37 and Alum groups conferred significant protection against SARS-CoV-2 infection in the pharynges, nares and in the bronchoalveolar lavage. The nAb titers were highly correlated with protection against infection. Furthermore, RBD-NP when used in conjunction with AS03 was as potent as the prefusion stabilized Spike immunogen, HexaPro. Taken together, these data highlight the efficacy of the RBD-NP formulated with clinically relevant adjuvants in promoting robust immunity against SARS-CoV-2 in non-human primates.
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The SARS-CoV-2 Spike glycoprotein mediates virus entry and is a major target for neutralizing antibodies. All current vaccines are based on the ancestral Spike with the goal of generating a protective neutralizing antibody response. Several novel SARS-CoV-2 variants with multiple Spike mutations have emerged, and their rapid spread and potential for immune escape have raised concerns. One of these variants, first identified in the United Kingdom, B.1.1.7 (also called VUI202012/01), contains eight Spike mutations with potential to impact antibody therapy, vaccine efficacy and risk of reinfection. Here we employed a lentivirus-based pseudovirus assay to show that variant B.1.1.7 remains sensitive to neutralization, albeit at moderately reduced levels (~2-fold), by serum samples from convalescent individuals and recipients of two different vaccines based on ancestral Spike: mRNA-1273 (Moderna), and protein nanoparticle NVX-CoV2373 (Novavax). Some monoclonal antibodies to the receptor binding domain (RBD) of Spike were less effective against the variant while others were largely unaffected. These findings indicate that B.1.1.7 is not a neutralization escape variant that would be a major concern for current vaccines, or for an increased risk of reinfection.
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Objective To investigate the gene expression difference of IFN and their receptors in peripheral blood mononuclear cells (PBMC) of pulmonary embolism (PE) patients.Methods Twenty cases of PE patients and twenty sex and age matched controls were recruited into the study.Human cDNA microarray analysis was used to detect the gene expression difference of IFN associated genes between the two groups,and random variance model corrected t test was used to analyze the statistical data.Results In comparison with the control group, mRNA expression of type Ⅰ IFN, including IFNα5 mRNA,IFNα6 mRNA,IFNα8 mRNA,IFNα14 mRNA,IFNκ mRNA,IFNω1 mRNA,IFNε1 mRNA in PBMC of PE patients Were down-regulated (P ＜ 0.05 ).There was no significant difference in gene expression of type Ⅰ IFN receptors IFNαR1 and IFNαR2 between the PE and control groups (P ＞ 0.05 ).In comparison with the control group,mRNA expression of IFNγ gene was down-regulated ( P ＜ 0.05 ).The mRNA expression of IFNγR1 and IFNγR2 genes were upregulated compared with the control (P ＞ 0.05 ).Conclusion mRNA expression of type Ⅰ and type Ⅱ IFN in PE are significantly down-regulated,but not the IFN receptors.Reduced immune function may play an important role in the PE patients who are susceptible to virus,intracellular bacteria and parasites.
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Objectives To investigate the expression of mTOR signaling pathway in pancreatic cancer and export its signification. Methods 6 samples of pancreatic cancer and its paracancerous tissues specimens confirmed by surgery and pathologic examination were selected. RNA was extracted and expression profiles experiment was performed by using Agilent human whole genomic oligonucleotide microarrays. The expression of mTOR signaling pathway in pancreatic cancer was analyzed by bioinformatics. Results Totally 1276 differential gene were selected, and 691 were up-regulated in cancer tissue, while 585 were down-regulated.The highest score of KEGG pathway's Enrichment and gene count was hsa04150 in mTOR signaling pathway,with its Enrichment of 4.5622519 and gene count of 9, and the percentage of gene count was 1.15%, the EASE Score P value was 6.23 E-04, which had the most biological significance. Among those, there was significantly difference of expression of nine key genes including ULK2, PIK3R3, PDPK1, EIF4EBP1, PGF,VEGFB, ULK3, RICTOR and PIK3 R5 (P ＜ 0.05). Conclusions The pathogenesis of pancreatic cancer is related to the activation of the mTOR signaling pathway.
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Objective To study the expression of PIWIL1, PIWIL3 and PIWIL4 in human colon cancer and its clinical significance. Methods We collected cancerous tissues and its adjacent tissues of 106 patients with colon cancer, two tissue microarrays were constructed, with 62 and 150 points respectively. We studied the expression of PIWIL1, PIWIL3 and PIWIL4 through immunohistochemistry. Results The expression of PIWIL1, PIWIL3 and PIWIL4 were significantly higher in cancerous tissues than those in adjacent tissues (P＜0. 01). In cancerous tissues and its adjacent tissues, postive correlation were seen among PIWIL1, PIWIL3 and PIWIL4 expression (P＜0. 01). PIWIL1 expression was significant higher in low differentiation group than that in high differentiation group (t =- 2. 840, P＜0.01 ). PIWIL3 expression was higher in high clinical stage than that in low clinical stage (F= 3. 112, P＜0.05). The expression of PIWIL3 and PIWIL4 were significantly higher in patients with colon cancer with distant metastasis than those without distant metastasis (t= -3. 349, P＜0.01 ; t = - 2. 168, P＜0. 05). PIWIL3 and PIWIL4 expression were correlated with occurring of colon cancer (P＜0. 01). Conclusions The expressions of PIWIL1,PIWIL3 and PIWIL4 in colon cancer were correlated with the differentiation, clinical stage and distant metastasis of colon cancer. PIWIL3 and PIWIL4 expression were two independent related factors of occurring of colon cancer, which would be furtherly investigated to be served as novel markers for early diagnosis and promising molecular targets for colon cancer therapy.
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Objective To investigate the microRNAs expression profile in human colorectal cancer with or without liver metastasis and try to screen miRNA associated with liver metastasis in colorectal cancer. Methods Twenty five surgical resected colorectal cancer specimens were collected and frozen in liquid nitrogen. Three without liver metastasis and three with liver metastasis were selected, from which total RNAs were isolated. The expressions of miRNAs in these two types of specimens were detected by illumine microRNA microarray, and the difference of miRNA expression was screened. The biochip results were verified with real-time RT-PCR in all colorectal caner specimens. Results The miRNA expression was significantly different in colorectal cancer with liver metastasis and without liver metastasis. Compared with colorectal cancer without liver metastasis, 28 miRNA expressions was different in colorectal cancer with liver metastasis, 4 up regulated and 24 down regulated. The quantity of miR-139-3p expression in colorectal cancer with liver metastasis was 1.75±0.40, up regulated compared with that incolorectal cancer without liver metastasis(0. 69 ±0.58,P＜0.05). The quantity of miR-19a expression in liver metastasis was 0. 39±0. 20, downregulated compare with no liver metastasis( 1.38 ± 0.98, P＜0. 05). The result of miRNA biochip was consistent with that of RT-PCR. Conclusion The difference of miRNA expression might relate to liver metastasis of colorectal cancer. The specific miRNAs expression profile might provide new target for diagnosis and treatment of colorectal cancer with liver metastasis.
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Objective To investigate the whole genomic expression profiles of chronic atrophic gastritis with interleukin(IL)-1β-31CC/-511TT genotype as measured by oligonucleotide microarray technique.Methods Genomic RNA was extracted from gastric biopsies of 12 patients with chronic atrophic gastritis(6 with IL-1β-31CC/-511TT and 6 with IL-1β-31TT/-511CC).The genomic profiles of IL-1β gene polymorphisms 31CC/-511TT and 31TT/-511CC were compared and tested for differential expressed genes associated with 31CC/-511TT using Agilent human whole genomic oligonucleotide microarrays.The results were further analyzed in terms of gene ontology(GO).Results There were 200 differentially expressed genes associated with IL-1β-31CC/-511TT,159 of which were up-regulated and 41 were down-regulated.These genes mainly involved in macromolecule metabolic process,post-translational protein modification,ubiquitin cycle,and protein kinase cascade.Five genes had biological activities,one of which was down-regulated gene(PCSK5)and 4 were upregulated genes(PRKCA,NPLOC4,TRIB3 and MAPKAPK3).Conclusions The chronic atrophic gastritis with IL-1β-31CC/-511TT genotype has molecular phenotypes which is associated with malignance and inflammation.These individuals are needed more intensive preemptive treatment and dynamic surveillance.
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genes related to pancreatic cancer was mainly associated with biological process,cellular location,molecular function,which suggested the development of pancreatic cancer was caused by multiple genes.
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ssociated genes,especially down-regulated expression of T cell mediated function genes,in patients with PE indicates that the etiology of PE might be related to viral infection.
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Objective To study the proliferation promoting effect on osteoblast cells induced by sodium orthovanadate and whether nitric oxide (NO) was involved in this process. Methods MTT assay was employed to determine cell proliferation and its inhibition. The level of NO was measured by enzyme reduction method. Results The MTT values of MC3T3-E1 cells under the 2.5,5.0,10.0 ?mol/L of sodium orthovanadate were 0.3380?0.0045, 0.3400?0.0141, 0.3840?0.0313 respectively, which were higher than in control group (0.2540?0.0167)(P
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Objective To study the therapeutic effect on murine allergic asthma with recombinant Bla g 2(rBla g 2) allergen and its possible mechanism.Methods Eighteen BALB/C mice were randomly divided into three groups:normal control group(group A) , asthma model group(group B) , and recombinant protein rBlag2 treatment group(group C).Mice in groups B and C were subcutaneously immunized weekly with rBla g 2(50 mg) formulated in Al(OH)3 adjuvant for three weeks.Group A received only adjuvant emulsified with normal saline.Two weeks after the last inoculation, mice in group C were administered each with rBla g 2(100 mg) /dose, and groups A and B were given PBS.All the mice received eight doses at 2-day intervals.One week after the last immunotherapy, mice in groups B and C were intranasally challenged with 50 mg rBla g 2 daily for seven days, while mice in group A received PBS.Twenty-four hours after the challenge, the following items were examined:airway hyperresponsiveness of mice, total cellular score and cell classification in bronchoalveolar lavage fluid(BALF) , level of rBla g 2-specific IgE and IgG2a in serum, lung inflammation by HE stain, and Bcl-2 expression of eosinophils of lung by immunohistochemistry.Results Compared with group B, group C showed a decreased Penh value of airway hyperresponsiveness(P