Publications by authors named "Liliang Xia"

13 Publications

  • Page 1 of 1

Knockdown of CDK5 down-regulates PD-L1 via the ubiquitination-proteasome pathway and improves antitumor immunity in lung adenocarcinoma.

Transl Oncol 2021 Sep 12;14(9):101148. Epub 2021 Jun 12.

Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai 200030, PR China. Electronic address:

Although immunotherapy (anti-PD-1/PD-L1 antibodies) has been approved for clinical treatment of lung cancer, only a small proportion of patients respond to monotherapy. Hence, understanding the regulatory mechanism of PD-L1 is particularly important to identify optimal combinations. In this study, we found that inhibition of CDK5 induced by shRNA or CDK5 inhibitor leads to reduced expression of PD-L1 protein in human lung adenocarcinoma cells, while the mRNA level is not substantially altered. The PD-L1 protein degradation is mediated by E3 ligase TRIM21 via ubiquitination-proteasome pathway. Subsequently, we studied the function of CDK5/PD-L1 axis in LUAD. In vitro, the absence of CDK5 in mouse Lewis lung cancer cell (LLC) has no effect on cell proliferation. However, the attenuation of CDK5 or combined with anti-PD-L1 greatly suppresses tumor growth in LLC implanted mouse models in vivo. Disruption of CDK5 elicits a higher level of CD3, CD4 and CD8 T cells in spleens and lower PD-1 expression in CD4 and CD8 T cells. Our findings highlight a role for CDK5 in promoting antitumor immunity, which provide a potential therapeutic target for combined immunotherapy in LUAD.
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http://dx.doi.org/10.1016/j.tranon.2021.101148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215302PMC
September 2021

Serum Metabolite Biomarkers Predictive of Response to PD-1 Blockade Therapy in Non-Small Cell Lung Cancer.

Front Mol Biosci 2021 21;8:678753. Epub 2021 May 21.

CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, China.

Despite remarkable success of immunotherapies with checkpoint blockade antibodies targeting programmed cell death protein 1 (PD-1), the majority of patients with non-small-cell lung cancer (NSCLC) have yet to receive durable benefits. We used the metabolomic profiling of early on-treatment serum to explore predictors of clinical outcomes of anti-PD-1 treatment in patients with advanced NSCLC. We recruited 74 Chinese patients who had stage IIIB/IV NSCLC-proven tumor progression and were treated with PD-1 inhibitor. The study was comprised of a discovery cohort of patients treated with nivolumab and two validation cohorts of patients receiving tislelizumab or nivolumab. Serum samples were collected 2-3 weeks after the first infusion of PD-1 inhibitor. Metabolomic profiling of serum was performed using ultrahigh performance lipid chromatograph-mass spectrometry. The serum metabolite biomarkers were identified using an integral workflow of nontargeted metabolomic data analysis. A serum metabolite panel consisting of hypoxanthine and histidine was identified and validated as a predictor of response to PD-1 blockade treatment in patients with advanced NSCLC. High levels of both hypoxanthine and histidine in early on-treatment serum were associated with improved progression-free survival [hazard ratio (HR) = 0.078, 95% confidence interval (CI), 0.027-0.221, 0.001] and overall survival (HR = 0.124, 95% CI, 0.039-0.397, 0.001) in the discovery cohort. The serum metabolite panel showed a high sensitivity and specificity in distinguishing responders and non-responders in the validation cohorts 1 and 2, with an area under the receiver-operating characteristic curve of 0.933 and 1.000, respectively. High levels of serum hypoxanthine and histidine were correlated with improved progression-free survival in the validation cohort 1 (HR = 0.137, 95% CI, 0.040-0.467, 0.001) and in the validation cohort 2 (HR = 0.084, 95% CI, 0.009-0.762, 0.028). Our results revealed that hypoxanthine and histidine in early on-treatment serum are predictive biomarkers of response to PD-1 blockade therapy in patients with advanced NSCLC. The serum biomarker panel would enable early identification of NSCLC patients who may benefit from PD-1 blockade therapy.
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http://dx.doi.org/10.3389/fmolb.2021.678753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176105PMC
May 2021

A multi-omics-based serial deep learning approach to predict clinical outcomes of single-agent anti-PD-1/PD-L1 immunotherapy in advanced stage non-small-cell lung cancer.

Am J Transl Res 2021 15;13(2):743-756. Epub 2021 Feb 15.

Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai, China.

Only 20% NSCLC patients benefit from immunotherapy with a durable response. Current biomarkers are limited by the availability of samples and do not accurately predict who will benefit from immunotherapy. To develop a unified deep learning model to integrate multimodal serial information from CT with laboratory and baseline clinical information. We retrospectively analyzed 1633 CT scans and 3414 blood samples from 200 advanced stage NSCLC patients who received single anti-PD-1/PD-L1 agent between April 2016 and December 2019. Multidimensional information, including serial radiomics, laboratory data and baseline clinical data, was used to develop and validate deep learning models to identify immunotherapy responders and nonresponders. A Simple Temporal Attention (SimTA) module was developed to process asynchronous time-series imaging and laboratory data. Using cross-validation, the 90-day deep learning-based predicting model showed a good performance in distinguishing responders from nonresponders, with an area under the curve (AUC) of 0.80 (95% CI: 0.74-0.86). Before immunotherapy, we stratified the patients into high- and low-risk nonresponders using the model. The low-risk group had significantly longer progression-free survival (PFS) (8.4 months, 95% CI: 5.49-11.31 . 1.5 months, 95% CI: 1.29-1.71; HR 3.14, 95% CI: 2.27-4.33; log-rank test, <0.01) and overall survival (OS) (26.7 months, 95% CI: 18.76-34.64 . 8.6 months, 95% CI: 4.55-12.65; HR 2.46, 95% CI: 1.73-3.51; log-rank test, <0.01) than the high-risk group. An exploratory analysis of 93 patients with stable disease (SD) [after first efficacy assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] also showed that the 90-day model had a good prediction of survival and low-risk patients had significantly longer PFS (11.1 months, 95% CI: 10.24-11.96 . 3.3 months, 95% CI: 0.34-6.26; HR 2.93, 95% CI: 1.69-5.10; log-rank test, P<0.01) and OS (31.7 months, 95% CI: 23.64-39.76 . 17.2 months, 95% CI: 7.22-27.18; HR 2.22, 95% CI: 1.17-4.20; log-rank test, =0.01) than high-risk patients. In conclusion, the SimTA-based multi-omics serial deep learning provides a promising methodology for predicting response of advanced NSCLC patients to anti-PD-1/PD-L1 monotherapy. Moreover, our model could better differentiate survival benefit among SD patients than the traditional RECIST evaluation method.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868825PMC
February 2021

Peripheral CD4 T cell signatures in predicting the responses to anti-PD-1/PD-L1 monotherapy for Chinese advanced non-small cell lung cancer.

Sci China Life Sci 2021 Jan 29. Epub 2021 Jan 29.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Limited benefit population of immune checkpoint inhibitors makes it urgent to screen predictive biomarkers for stratifying the patients. Herein, we have investigated peripheral CD4 T cell signatures in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-1/PD-L1 treatments. It was found that the percentages of IFN-γ and IL-17A secreting naïve CD4 T cells (Tn), and memory CD4 T cells (Tm) expressing PD-1, PD-L1 and CTLA-4 were significantly higher in responder (R) than non-responder (NonR) NSCLC patients associated with a longer progression free survival (PFS). Logistic regression analysis revealed that the baseline IFN-γ-producing CD4 Tn cells and PD-1CD4 Tm cells were the most significant signatures with the area under curve (AUC) value reaching 0.849. This was further validated in another anti-PD-1 monotherapy cohort. Conversely, high percentage of CTLA-4CD4 Tm cells was associated with a shorter PFS in patients receiving anti-PD-L1 monotherapy. Our study therefore elucidates the significance of functional CD4 Tn and Tm subpopulations before the treatment in predicting the responses to anti-PD-1 treatment in Chinese NSCLC patients. The fact that there display distinct CD4 T cell signatures in the prediction to anti-PD-1 and anti-PD-L1 monotherapy from our study provides preliminary evidence on the feasibility of anti-PD-1 and anti-PD-L1 combination therapy for advanced NSCLC patients.
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http://dx.doi.org/10.1007/s11427-020-1861-5DOI Listing
January 2021

Identification of Mutated Peptides in Bladder Cancer From Exomic Sequencing Data Reveals Negative Correlation Between Mutation-Specific Immunoreactivity and Inflammation.

Front Immunol 2020 30;11:576603. Epub 2020 Nov 30.

Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Introduction And Objective: Neoantigen-based immunotherapy is one of the breakthroughs in cancer immunotherapy. Benefit from the Cancer Genome Atlas database, we intended to identify mutant peptides with neoantigen property in bladder cancer (BC). Correlations between the immunoreactivity of candidate neoantigens and clinical manifestations were further analyzed.

Methods: HLA-A*02:01 restricted mutant (MT) and wildtype (WT) peptides were predicted by using whole exome sequencing data of 412 BC patients in the TCGA database. Binding affinity to HLA-A2 molecules was determined by using T2 cell-based binding assay. The immunoreactivity to WT and MT peptides in HLA-A2 BC patients was determined by using an ELISPOT assay upon stimulation with MT and WT peptides individually. Clinical relevance to peptide-specific immunoreactivity was analyzed by Pearson correlation analysis. The disease free survival (DFS) curves were plotted using the Kaplan-Meier method in BC patients with or without mutations and compared using the log-rank test online.

Results: Fifty-seven HLA-A*02:01 restricted WT and MT peptides were selected based on predicted high affinity and expression frequency, among which 12 MT peptides from 12 individual genes exhibited strong affinity to HLA-A2 molecules when compared to WT counterparts. MT peptides induced more peptide-specific IFNγ spot forming units (SFUs) than WT counterparts in HLA-A2 BC patients upon stimulation. They were negatively correlated to the counts of peripheral leukocytes and platelets. Patients with higher C-reactive protein level exhibited lower immunoreactivity to MT peptides. Combination of MT peptides from 6 genes, including , , , , and covered 47.5% of the patients under investigation. Patients harboring combinational mutations in these genes were associated with a longer DFS according to the cBioportal online analysis.

Conclusion: Twelve HLA-A*02:01 restricted MT peptides have been identified exhibiting higher binding affinity to HLA-A2 molecules and stronger immunoreactivity than WT counterparts in BC patients. Combination of MT peptides from six genes might be potential as neoantigen candidates in cancer immunotherapy against BC in the future. Inflammatory modulation is inclined to be a strategy to enhance the efficacy of neoantigen-based immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2020.576603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734250PMC
June 2021

The Diversity of Gut Microbiome is Associated With Favorable Responses to Anti-Programmed Death 1 Immunotherapy in Chinese Patients With NSCLC.

J Thorac Oncol 2019 08 23;14(8):1378-1389. Epub 2019 Apr 23.

Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Introduction: Gut microbiome affecting the responses to immune checkpoint inhibitors against advanced NSCLC has been investigated in the Western population. However, considering pre-existing genetic and gut microbiota variation, the relevance remains unknown in the East-Asian NSCLC population. This study is designed to explore the relationship between gut microbiome and clinical outcomes in Chinese patients with NSCLC who have received treatment using an anti-programmed death 1 (PD-1) blockade.

Methods: Thirty-seven patients with advanced NSCLC receiving treatment with nivolumab were enrolled in CheckMate 078 (NCT02613507) and CheckMate 870 (NCT03195491). Fecal samples were collected at the starting point, when patients received nivolumab, at clinical evaluation, and when disease progression was noted. 16S ribosome RNA gene sequencing was applied to assess gut microbiota profiles. Peripheral immune signatures were determined by multicolor flow cytometry in parallel.

Results: When subgrouping patients into responder (R) and nonresponder according to the clinical response assessed using Response Evaluation Criteria in Solid Tumor version 1.1, R patients harbored higher diversity of gut microbiome at the starting point with stable composition during the treatment. Patients with high microbiome diversity had significantly prolonged progression-free survival when compared to those with low diversity. Compositional difference was observed between the two groups as well with the enrichment of Alistipes putredinis, Bifidobacterium longum, and Prevotella copri in R whereas Ruminococcus_unclassified enriched in nonresponding patients. Analysis of systemic immune responses using multicolor flow cytometry revealed that patients with a high abundance of microbiome diversity in the gut had a greater frequency of unique memory CD8 T cell and natural killer cell subsets in the periphery in response to anti-PD-1 therapy.

Conclusions: Our results reveal strong correlation between gut microbiome diversity and the responses to anti-PD-1 immunotherapy in Chinese patients with advanced NSCLC. Patients with favorable gut microbiome (such as those with high diversity) exhibit enhanced memory T cell and natural killer cell signatures in the periphery. These findings provide important implications for the prediction and the evaluation of anti-PD-1 immunotherapy against NSCLC in the Chinese population.
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http://dx.doi.org/10.1016/j.jtho.2019.04.007DOI Listing
August 2019

PD-1/PD-L1 Blockade Therapy in Advanced Non-Small-Cell Lung Cancer: Current Status and Future Directions.

Oncologist 2019 02;24(Suppl 1):S31-S41

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China

The use of immune checkpoint inhibitors (ICIs) has become one of the most promising approaches in the field of cancer therapy. Unlike the current therapies that target tumor cells, such as chemotherapy, radiotherapy, or targeted therapy, ICIs directly restore the exhausted host antitumor immune responses mediated by the tumors. Among multiple immune modulators identified, the programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) axis leading to the exhaustion of T-cell immunity in chronic infections and tumors has been widely investigated. Therefore, blocking antibodies targeting PD-1 or PD-L1 have been developed and approved for the treatment of various advanced cancers, including non-small-cell lung cancer (NSCLC), making them the most successful ICIs. Compared with chemotherapy or radiotherapy, PD-1/PD-L1 blockade therapy significantly improves the durable response rate and prolongs long-term survival with limited adverse effects in both monotherapy and combination therapy for advanced NSCLC. However, extensive challenges exist for further clinical applications, such as a small fraction of benefit population, primary and acquired resistance, the lack of predictive and prognostic biomarkers, and treatment-related adverse effects. In this article, we summarize the latest clinical applications of PD-1/PD-L1 blockade therapy in advanced NSCLC worldwide, as well as in China, and discuss the bottlenecks related to the use of this therapy in clinical practice. An exploration of the underlying mechanism of PD-1/PD-L1 blockade therapy and biomarker identification will maximize the application of ICIs in advanced NSCLC and facilitate bedside-to-bench studies in cancer immunotherapy as well. IMPLICATIONS FOR PRACTICE: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) display apparent benefits for the treatment of advanced non-small-cell lung cancer (NSCLC). However, the clinical applications of these therapies are challenged by the limited benefit population with additional high economic burden and adverse events. This review discusses the bottlenecks of ICI therapy in clinical practice and provides appropriate guidance in the development of predictive biomarkers, the establishment of the criteria for combining PD-1/PD-L1 blockade therapy with the existing therapies, and the management of adverse events observed both in monotherapy and combination therapy, which will help maximize the applications of ICIs in advanced NSCLC.
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http://dx.doi.org/10.1634/theoncologist.2019-IO-S1-s05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394772PMC
February 2019

Identification of HLA-A2-Restricted Mycobacterial Lipoprotein Z Peptides Recognized by T CellsFrom Patients With ActiveTuberculosis Infection.

Front Microbiol 2018 21;9:3131. Epub 2018 Dec 21.

Department of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Identification of HLA-restricted peptides derived from mycobacterial antigens that are endowed with high affinity and strong antigenicity is not only of interest in tuberculosis (TB) diagnostics and treatment efficacy evaluation, but might also provide potential candidates for the development of therapeutic vaccines against drug-resistant TB. Our previous work demonstrated that lipoprotein Z (LppZ) displayed high immunogenicity and antigenicity in active TB patients. In the present study, ten HLA-A2-restricted LppZ peptides (LppZp1-10) were predicted by bioinformatics, among which LppZp7 and LppZp10 were verified to possess high affinity to HLA-A2 molecules using T2 cell-based affinity binding assay. Moreover, results from ELISpot assay showed that both LppZp7 and LppZp10 peptides were able to induce more IFN-γ producing cells upon stimulation of PBMC from HLA-A2 active TB (ATB) patients as compared to those from healthy controls (HCs). Also, the numbers of LppZp7 and LppZp10-specific IFN-γ producing cells exhibited positive correlations with those of ESAT-6 peptide (E6p) or CFP-10 peptide (C10p) in ATB. Interestingly, stimulation with LppZp7/p10 mixture was able to induce higher intracellular expression of IFN-γ and IL-2 cytokines in CD8 and CD4 T cells from ATB as compared to HC, associated with lower expression of TNF-α in both CD8 and CD4 T cells. Taken together, HLA-A2-restricted LppZp7 and LppZp10 peptides display high immunoreactivity in HLA-matched ATB patients demonstrated by high responsiveness in both CD8 and CD4 T cells. With the ability to induce strong antigen-specific cellular responses, LppZp7 and LppZp10 are of potential value for the future applications in the prevention and control of TB.
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http://dx.doi.org/10.3389/fmicb.2018.03131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308912PMC
December 2018

PD-1 blockade augments humoral immunity through ICOS-mediated CD4 T cell instruction.

Int Immunopharmacol 2019 Jan 16;66:127-138. Epub 2018 Nov 16.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Successful applications of PD-1/PD-L1 blockade in multiple cancers highlight the efficacy of immunotherapy mediated by enhancing CD8 T cell immunity both in mouse and human. How PD-1 blockade affects humoral immunity remains unclear. Herein we demonstrated that treatment of anti-PD-1 antibody led to the increase in both total IgG and OVA-specific IgG in OVA-immunized mice. However, no effect was observed on Ab affinity maturation. Accumulation of germinal center (GC) and memory B cells was observed in the spleens together with elevated percentages of plasma cells in the spleens and bone marrow. More interestingly, dramatic infiltration of CD4 T cells was apparent in GCs after PD-1 blockade with a significant increase in the expression of ICOS. When CD4 T cells and B cells from OVA-immunized mice were co-cultured with neutralizing anti-PD-1 Ab in vitro, PD-1 blockade recapitulated the up-regulation of ICOS expression on CD4 T cells with the activation of ERK signaling. Suppression of ERK activation not only reduced ICOS expression on CD4 T cells but also attenuated IgG production upon PD-1 blockade. Taken together, PD-1 blockade enhances humoral immunity. This process partially relies on more accumulation of CD4 T cells in GCs with the up-regulation of ICOS expression and the promotion of B cell terminal differentiation. The regulatory pattern of PD-1 blockade illustrated here provides a new mechanism of how immune checkpoint molecules regulating humoral immune responses.
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http://dx.doi.org/10.1016/j.intimp.2018.10.045DOI Listing
January 2019

Development of VHH antibodies against dengue virus type 2 NS1 and comparison with monoclonal antibodies for use in immunological diagnosis.

PLoS One 2014 21;9(4):e95263. Epub 2014 Apr 21.

Institute of Life Science, General Hospital of The People's Liberation Army, Beijing, PR China.

The possibility of using variable domain heavy-chain antibodies (VHH antibodies) as diagnostic tools for dengue virus (DENV) type 2 NS1 protein was investigated and compared with the use of conventional monoclonal antibodies. After successful expression of DENV type 2 NS1 protein, the genes of VHH antibodies against NS1 protein were biopanned from a non-immune llama library by phage display. VHH antibodies were then expressed and purified from Escherichia coli. Simultaneously, monoclonal antibodies were obtained by the conventional route. Sequence analysis of the VHH antibodies revealed novel and long complementarity determining regions 3 (CDR3). Epitope mapping was performed via a phage display peptide library using purified VHH and monoclonal antibodies as targets. Interestingly, the same region of NS1, which comprises amino acids 224HWPKPHTLW232, was conserved for both kinds of antibodies displaying the consensus motif histidine-tryptophan-tryptophan or tryptophan-proline-tryptophan. The two types of antibodies were used to prepare rapid diagnostic kits based on immunochromatographic assay. The VHH antibody immobilized rapid diagnostic kit showed better sensitivity and specificity than the monoclonal antibody immobilized rapid diagnostic kit, which might be due to the long CDR3 regions of the VHH antibodies and their ability to bind to the pocket and cleft of the targeted antigen. This demonstrates that VHH antibodies are likely to be an option for developing point-of-care tests against DENV infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0095263PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994031PMC
January 2015

A high-affinity CDR-grafted antibody against influenza A H5N1 viruses recognizes a conserved epitope of H5 hemagglutinin.

PLoS One 2014 18;9(2):e88777. Epub 2014 Feb 18.

Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China ; Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Highly pathogenic avian influenza (HPAI) H5N1 virus infection is still a potential threat to public health worldwide. While vaccines and antiviral drugs are currently under development, neutralizing antibodies could offer an alternative strategy to prevent and treat H5N1 virus infection. In the present study, we had developed a humanized antibody against H5N1 viruses from mouse-derived hybridoma in order to minimize its immunogenicity for potential clinical application. The humanized antibody hH5M9 was generated by transferring the mouse complementarity determining region (CDR) residues together with four key framework region (FR) residues onto the FR of the human antibody. This humanized antibody exhibited high affinity and specificity comparable to the parental mouse or chimeric counterpart with broad and strong neutralization activity against all H5N1 clades and subclades except for Egypt clades investigated. Furthermore, through epitope mapping we identified a linear epitope on the top region of hemagglutinin (HA) that was H5N1 specific and conserved. Our results for the first time reported a humanized antibody against H5N1 viruses by CDR grafting method. With the expected lower immunogenicity, this humanized antibody was expected to be more efficacious than murine or human-mouse chimeric antibodies for future application in humans.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088777PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928294PMC
December 2014

Complete Genome Sequence of an Acinetobacter Strain Harboring the NDM-1 Gene.

Genome Announc 2013 Apr 18;1(2):e0002312. Epub 2013 Apr 18.

Institute of Military Veterinary, AMMS, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun, China;

The NDM-1 gene is a significant public health concern. Acinetobacter is one of the most prevalent opportunistic pathogens causing recent nosocomial infections with NDM-1, and drug-resistant strains pose serious threats to public health worldwide. Herein, we present the genomic sequence of Acinetobacter calcoaceticus subsp. anitratus XM1570, a multidrug-resistant isolate that carries the blaNDM-1 gene.
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http://dx.doi.org/10.1128/genomeA.00023-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630397PMC
April 2013

Seroepidemiology and genetic characterization of hepatitis E virus in the northeast of China.

Infect Genet Evol 2009 Jul 27;9(4):554-61. Epub 2009 Feb 27.

School of Life Science and Technology, Changchun University of Science and Technology, Changchun, PR China.

The aim of this study was to analyze the prevalence of infection and genotype of hepatitis E virus (HEV) in people and animals in the northeast of China (Heilongjiang, Jilin and Liaoning provinces). This seroepidemiological study was conducted using enzyme immunoassays and human sera positive for HEV antigen or anti-HEV IgM, and animal sera positive for HEV antigen or with an S/CO
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http://dx.doi.org/10.1016/j.meegid.2009.02.008DOI Listing
July 2009
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