82 results found
Zhang X, Lu S, Li H, et al., 2020, Viral and Antibody Kinetics of COVID-19 Patients with Different Disease Severities in Acute and Convalescent Phases: A 6-Month Follow-Up Study, VIROLOGICA SINICA, Vol: 35, Pages: 820-829, ISSN: 1674-0769
Lou H, Wojciak-Stothard B, Ruseva MM, et al., 2020, Autoantibody-dependent amplification of inflammation in SLE, Cell Death and Disease, Vol: 11, ISSN: 2041-4889
Anti-double stranded DNA antibodies (anti-dsDNA) are a hallmark of SLE but their role in disease pathogenesis is not fully resolved. Anti-dsDNA in serum are highly heterogeneous therefore in this study, we aimed to dissect the functional specificities of anti-dsDNA using a panel of human monoclonal antibodies (humAbs) generated from patients with active lupus nephritis. A total of 46 ANA reactive humAbs were isolated and divided into four broad classes based on their reactivity to histones, DNA and Crithidia. Functional analysis indicated that one subclass of antibodies bound strongly to decondensed DNA areas in neutrophil extracellular traps (NETs) and protected NETs from nuclease digestion, similar to the sera from active SLE patients. In addition, these anti-dsDNA antibodies could stimulate type I interferon responses in mononuclear phagocytic cells, or NF-kB activity in endothelial cells, by uptake of NETs-anti-NETs immune complexes and subsequently trigging inflammatory responses in an Fc-gamma receptor (Fcg-R)-dependant manner. Together our data suggest that only a subset of anti-dsDNA antibodies is capable to amplify inflammatory responses by deposit in the nephritic kidney in vivo, protecting NETs digestion as well as uptake of NETs immune complexes into Fcg-R-expressing cells in vitro.
Cheng L, Yu H, Wrobel JA, et al., 2020, Identification of pathogenic TRAIL-expressing innate immune cells during HIV-1 infection in humanized mice by scRNA-Seq., JCI Insight, Vol: 5
Depletion of CD4+ T cells during HIV-1 infection is mostly mediated by inflammatory cells via indirect but not clearly defined mechanisms. In this report, we used single-cell RNA-Seq (scRNA-Seq) technology to study HIV-induced transcriptomic change in innate immune cells in lymphoid organs. We performed scRNA-Seq on hCD45+hCD3-hCD19- human leukocytes isolated from spleens of humanized NOD/Rag2-/-γc-/- (NRG) mice transplanted with human CD34+ hematopoietic stem progenitor cells (NRG-hu HSC mice). We identified major populations of innate immune cells, including plasmacytoid dendritic cells (pDCs), myeloid dendritic cells (mDCs), macrophages, NK cells, and innate lymphoid cells (ILCs). HIV-1 infection significantly upregulated genes involved in type I IFN inflammatory pathways in each of the innate immune subsets. Interestingly, we found that TRAIL was upregulated in the innate immune populations, including pDCs, mDCs, macrophages, NK cells, and ILCs. We further demonstrated that blockade of the TRAIL signaling pathway in NRG-hu HSC mice prevented HIV-1-induced CD4+ T cell depletion in vivo. In summary, we characterized HIV-induced transcriptomic changes of innate immune cells in the spleen at single-cell levels, identified the TRAIL+ innate immune cells, and defined an important role of the TRAIL signaling pathway in HIV-1-induced CD4+ T cell depletion in vivo.
Rijal P, Elias SC, Machado SR, et al., 2019, Therapeutic monoclonal antibodies for Ebola virus infection derived from vaccinated humans, Cell Reports, Vol: 27, Pages: 172-186.e7, ISSN: 2211-1247
We describe therapeutic monoclonal antibodies isolated from human volunteers vaccinated with recombinant adenovirus expressing Ebola virus glycoprotein (EBOV GP) and boosted with modified vaccinia virus Ankara. Among 82 antibodies isolated from peripheral blood B cells, almost half neutralized GP pseudotyped influenza virus. The antibody response was diverse in gene usage and epitope recognition. Although close to germline in sequence, neutralizing antibodies with binding affinities in the nano- to pico-molar range, similar to “affinity matured” antibodies from convalescent donors, were found. They recognized the mucin-like domain, glycan cap, receptor binding region, and the base of the glycoprotein. A cross-reactive cocktail of four antibodies, targeting the latter three non-overlapping epitopes, given on day 3 of EBOV infection, completely protected guinea pigs. This study highlights the value of experimental vaccine trials as a rich source of therapeutic human monoclonal antibodies.
Wang FS, Zhang L, Douek D, et al., 2018, Strategies for an HIV cure: progress and challenges, NATURE IMMUNOLOGY, Vol: 19, Pages: 1155-1158, ISSN: 1529-2908
Kelleher P, Xu X-N, 2018, Hard-to-kill macrophages lead to chronic inflammation in HIV., Nat Immunol, Vol: 19, Pages: 433-434
Kaslow DC, Kalil J, Bloom D, et al., 2017, The role of vaccines and vaccine decision-making to achieve the goals of the Grand Convergence in public health., Vaccine, Vol: 35 Suppl 1, Pages: A10-A15
On 17 and 18 July 2015, a meeting in Siena jointly sponsored by ADITEC and GlaxoSmithKline (GSK) was held to review the goals of the Global Health 2035 Grand Convergence, to discuss current vaccine evaluation methods, and to determine the feasibility of reaching consensus on an assessment framework for comprehensively and accurately capturing the full benefits of vaccines. Through lectures and workshops, participants reached a consensus that Multi-Criteria-Decision-Analysis is a method suited to systematically account for the many variables needed to evaluate the broad benefits of vaccination, which include not only health system savings, but also societal benefits, including benefits to the family and increased productivity. Participants also agreed on a set of "core values" to be used in future assessments of vaccines for development and introduction. These values include measures of vaccine efficacy and safety, incident cases prevented per year, the results of cost-benefit analyses, preventable mortality, and the severity of the target disease. Agreement on this set of core assessment parameters has the potential to increase alignment between manufacturers, public health agencies, non-governmental organizations (NGOs), and policy makers (see Global Health 2035 Mission Grand Convergence ). The following sections capture the deliberations of a workshop (Working Group 4) chartered to: (1) review the list of 24 parameters selected from SMART vaccines (see the companion papers by Timmis et al. and Madhavan et al., respectively) to determine which represent factors (see Table 1) that should be taken into account when evaluating the role of vaccines in maximizing the success of the Global Health 2035 Grand Convergence; (2) develop 3-5 "core values" that should be taken into account when evaluating vaccines at various stages of development; and (3) determine how vaccines can best contribute to the Global Health 2035 Grand Convergence effort.
Wang Q, Yang H, Liu X, et al., 2016, Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus, Science Translational Medicine, Vol: 8, ISSN: 1946-6234
The 2015–2016 outbreak of Zika virus (ZIKV) disease has affected many countries and is a major public health concern. ZIKV is associated with fetal microcephaly and neurological complications, and countermeasures are needed to treat and prevent ZIKV infection. We report the isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV. Two of the isolated antibodies (Z23 and Z3L1) demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of dengue virus, the closest relative to ZIKV. These two antibodies provided postexposure protection to mice in vivo. Structural studies revealed that Z23 and Z3L1 bound to tertiary epitopes in envelope protein domain I, II, or III, indicating potential targets for ZIKV-specific therapy. Our results suggest the potential of antibody-based therapeutics and provide a structure-based rationale for the design of future ZIKV-specific vaccines.
Jonsson P, Southcombe JH, Santos AM, et al., 2016, Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions, Proceedings of the National Academy of Sciences of the United States of America, Vol: 113, Pages: 5682-5687, ISSN: 1091-6490
The αβ T-cell coreceptor CD4 enhances immune responses more than 1 million-fold in some assays, and yet the affinity of CD4 for its ligand, peptide-major histocompatibility class II (pMHC II) on antigen-presenting cells, is so weak that it was previously unquantifiable. Here, we report that a soluble form of CD4 failed to bind detectably to pMHC II in surface plasmon resonance-based assays, establishing a new upper limit for the solution affinity at 2.5 mM. However, when presented multivalently on magnetic beads, soluble CD4 bound pMHC II-expressing B cells, confirming that it is active and allowing mapping of the native coreceptor binding site on pMHC II. Whereas binding was undetectable in solution, the affinity of the CD4/pMHC II interaction could be measured in 2D using CD4- and adhesion molecule-functionalized, supported lipid bilayers, yielding a 2D Kd of ∼5,000 molecules/μm2. This value is two to three orders of magnitude higher than previously measured 2D Kd values for interacting leukocyte surface proteins. Calculations indicated, however, that CD4/pMHC II binding would increase rates of T-cell receptor (TCR) complex phosphorylation by threefold via the recruitment of Lck, with only a small, 2–20% increase in the effective affinity of the TCR for pMHC II. The affinity of CD4/pMHC II therefore seems to be set at a value that increases T-cell sensitivity by enhancing phosphorylation, without compromising ligand discrimination.
Chen Y, Li N, Zhang T, et al., 2015, Comprehensive Characterization of the Transmitted/Founder env Genes From a Single MSM Cohort in China, JAIDS-Journal of Acquired Immune Deficiency Syndromes, Vol: 69, Pages: 403-412, ISSN: 1944-7884
Background: The men having sex with men (MSM) population has become one of the major risk groups for HIV-1 infection in China. However, the epidemiological patterns, function of the env genes, and autologous and heterologous neutralization activity in the same MSM population have not been systematically characterized.Methods: The env gene sequences were obtained by the single genome amplification. The time to the most recent common ancestor was estimated for each genotype using the Bayesian Markov Chain Monte Carlo approach. Coreceptor usage was determined in NP-2 cells. Neutralization was analyzed using Env pseudoviruses in TZM-bl cells.Results: We have obtained 547 full-length env gene sequences by single genome amplification from 30 acute/early HIV-1–infected individuals in the Beijing MSM cohort. Three genotypes (subtype B, CRF01_AE, and CRF07_BC) were identified and 20% of the individuals were infected with multiple transmitted/founder (T/F) viruses. The tight clusters of the MSM sequences regardless of geographic origins indicated nearly exclusive transmission within the MSM population and limited number of introductions. The time to the most recent common ancestor for each genotype was 10–15 years after each was first introduced in China. Disparate preferences for coreceptor usages among 3 genotypes might lead to the changes in percentage of different genotypes in the MSM population over time. The genotype-matched and genotype-mismatched neutralization activity varied among the 3 genotypes.Conclusions: The identification of unique characteristics for transmission, coreceptor usage, neutralization profile, and epidemic patterns of HIV-1 is critical for the better understanding of transmission mechanisms, development of preventive strategies, and evaluation of vaccine efficacy in the MSM population in China.
Armitage AE, Stacey AR, Giannoulatou E, et al., 2014, Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 111, Pages: 12187-12192, ISSN: 0027-8424
Gao S, Yang C, Jiang S, et al., 2014, Applications of RNA interference high-throughput screening technology in cancer biology and virology, Protein and Cell, Vol: 5, Pages: 805-815, ISSN: 1674-8018
RNA interference (RNAi) is an ancient intra-cellular mechanism that regulates gene expression and cell function. Large-scale gene silencing using RNAi high-throughput screening (HTS) has opened an exciting frontier to systematically study gene function in mammalian cells. This approach enables researchers to identify gene function in a given biological context and will provide considerable novel insight. Here, we review RNAi HTS strategies and applications using case studies in cancer biology and virology.
Huang K-YA, Li CK-F, Clutterbuck E, et al., 2014, Virus-Specific Antibody Secreting Cell, Memory B-cell, and Sero-Antibody Responses in the Human Influenza Challenge Model, JOURNAL OF INFECTIOUS DISEASES, Vol: 209, Pages: 1354-1361, ISSN: 0022-1899
Johri AK, Lata H, Yadav P, et al., 2013, Epidemiology of Group B Streptococcus in developing countries, VACCINE, Vol: 31, Pages: D43-D45, ISSN: 0264-410X
Li CK-F, Rappuoli R, Xu X-N, 2013, Correlates of protection against influenza infection in humans - on the path to a universal vaccine?, CURRENT OPINION IN IMMUNOLOGY, Vol: 25, Pages: 470-476, ISSN: 0952-7915
Zhang X, Huang X, Xia W, et al., 2013, HLA-B star 44 Is Associated with a Lower Viral Set Point and Slow CD4 Decline in a Cohort of Chinese Homosexual Men Acutely Infected with HIV-1, CLINICAL AND VACCINE IMMUNOLOGY, Vol: 20, Pages: 1048-1054, ISSN: 1556-6811
Li W-H, Li C-Y, Yang H-B, et al., 2013, Human leucocyte antigen-Bw4 and Gag-specific T cell responses are associated with slow disease progression in HIV-1B-infected anti-retroviral therapy-naive Chinese, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 171, Pages: 298-306, ISSN: 0009-9104
Zhou D, Zhang X, Li W, et al., 2013, Short Communication Broader T Cell Responses Directed Against Human Immunodeficiency Virus Type 1 in Infected Chinese Individuals Through Blood-Borne Transmission in Comparison with Mucosal Transmission, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 29, Pages: 89-93, ISSN: 0889-2229
Huang X, Lodi S, Fox Z, et al., 2013, Rate of CD4 decline and HIV-RNA change following HIV seroconversion in men who have sex with men: a comparison between the Beijing PRIMO and CASCADE cohorts, J Acquir Immune Defic Syndr, Vol: 62, Pages: 441-446, ISSN: 1944-7884
Perkins MR, Ryschkewitsch C, Liebner JC, et al., 2012, Changes in JC virus-specific T cell responses during natalizumab treatment and in natalizumab-associated progressive multifocal leukoencephalopathy, PLoS Pathogens, Vol: 8, ISSN: 1553-7366
Progressive multifocal leukoencephalopathy (PML) induced by JC virus (JCV) is a risk for natalizumab-treated multiple sclerosis (MS) patients. Here we characterize the JCV-specific T cell responses in healthy donors and natalizumab-treated MS patients to reveal functional differences that may account for the development of natalizumab-associated PML. CD4 and CD8 T cell responses specific for all JCV proteins were readily identified in MS patients and healthy volunteers. The magnitude and quality of responses to JCV and cytomegalovirus (CMV) did not change from baseline through several months of natalizumab therapy. However, the frequency of T cells producing IL-10 upon mitogenic stimulation transiently increased after the first dose. In addition, MS patients with natalizumab-associated PML were distinguished from all other subjects in that they either had no detectable JCV-specific T cell response or had JCV-specific CD4 T cell responses uniquely dominated by IL-10 production. Additionally, IL-10 levels were higher in the CSF of individuals with recently diagnosed PML. Thus, natalizumab-treated MS patients with PML have absent or aberrant JCV-specific T cell responses compared with non-PML patients, and changes in T cell-mediated control of JCV replication may be a risk factor for developing PML. Our data suggest further approaches to improved monitoring, treatment and prevention of PML in natalizumab-treated patients.
Li D, Hong A, Lu Q, et al., 2012, A novel role of CD1c in regulating CD1d-mediated NKT cell recognition by competitive binding to Ig-like transcript 4, INTERNATIONAL IMMUNOLOGY, Vol: 24, Pages: 729-737, ISSN: 0953-8178
Yang H, Wu H, Hancock G, et al., 2012, Antiviral Inhibitory Capacity of CD8+ T cells Predicts the Rate of CD4+ T-Cell Decline in HIV-1 Infection, JOURNAL OF INFECTIOUS DISEASES, Vol: 206, Pages: 552-561, ISSN: 0022-1899
Rajapaksa US, Li D, Peng Y-C, et al., 2012, HLA-B may be more protective against HIV-1 than HLA-A because it resists negative regulatory factor (Nef) mediated down-regulation, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 13353-13358, ISSN: 0027-8424
Wilkinson TM, Li CKF, Chui CSC, et al., 2012, Preexisting influenza-specific CD4(+) T cells correlate with disease protection against influenza challenge in humans, NATURE MEDICINE, Vol: 18, Pages: 274-280, ISSN: 1078-8956
Haig NA, Guan Z, Li D, et al., 2011, Identification of Self-lipids Presented by CD1c and CD1d Proteins, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 286, Pages: 37692-37701
Zhang Y, Peng Y, Yan H, et al., 2011, Multilayered Defense in HLA-B51-Associated HIV Viral Control, JOURNAL OF IMMUNOLOGY, Vol: 187, Pages: 684-691, ISSN: 0022-1767
Wu J, Zhong X, Li CK-F, et al., 2011, Optimal vaccination strategies for 2009 pandemic H1N1 and seasonal influenza vaccines in humans, VACCINE, Vol: 29, Pages: 1009-1016, ISSN: 0264-410X
Liu W, de Vlas SJ, Tang F, et al., 2010, Clinical and Immunological Characteristics of Patients with 2009 Pandemic Influenza A (H1N1) Virus Infection after Vaccination, CLINICAL INFECTIOUS DISEASES, Vol: 51, Pages: 1028-1032, ISSN: 1058-4838
Shu Y, Li CK-F, Li Z, et al., 2010, Avian Influenza A(H5N1) Viruses Can Directly Infect and Replicate in Human Gut Tissues, JOURNAL OF INFECTIOUS DISEASES, Vol: 201, Pages: 1173-1177, ISSN: 0022-1899
Freundt EC, Yu L, Goldsmith CS, et al., 2010, The Open Reading Frame 3a Protein of Severe Acute Respiratory Syndrome-Associated Coronavirus Promotes Membrane Rearrangement and Cell Death, JOURNAL OF VIROLOGY, Vol: 84, Pages: 1097-1109, ISSN: 0022-538X
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