scholarly journals COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters

2021 ◽  
Author(s):  
Zhaowei Xu ◽  
Yang Li ◽  
Qing Lei ◽  
Likun Huang ◽  
Dan-yun Lai ◽  
...  
Keyword(s):  
Immune Responses ◽  
Humoral Immunity ◽  
Clinical Parameters ◽  
Single Group ◽  
Analysis Pipeline ◽  
Humoral Immune ◽  
Start Button ◽  
One Stop ◽  
Specific Igg ◽  
The One

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the START button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.

scholarly journals COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters

2021 ◽  
Author(s):  
Zhaowei Xu ◽  
Yang Li ◽  
Qing Lei ◽  
Likun Huang ◽  
Dan-yun Lai ◽  
...  
Keyword(s):  
Immune Responses ◽  
Humoral Immunity ◽  
Clinical Parameters ◽  
Single Group ◽  
Analysis Pipeline ◽  
Humoral Immune ◽  
Start Button ◽  
One Stop ◽  
Specific Igg ◽  
The One

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the START button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.

TLR4 regulates rabies virus-induced humoral immunity through recruitment of cDC2 to lymph organs

2021 ◽  
Author(s):  
Chen Chen ◽  
Chengguang Zhang ◽  
Haoqi Li ◽  
Zongmei Wang ◽  
Yueming Yuan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Rabies Virus ◽  
Humoral Immunity ◽  
Humoral Immune Response ◽  
Critical Role ◽  
Wild Type ◽  
Humoral Immune ◽  
Specific Igg ◽  
Molecular Patterns

Rabies, caused by rabies virus (RABV), is fatal to both humans and animals around the world. Effective clinical therapy for rabies has not been achieved, and vaccination is the most effective means of preventing and controlling rabies. Although different vaccines, such as live attenuated and inactivated vaccines, can induce different immune responses, different expression of pattern recognition receptors (PRRs) also causes diverse immune responses. Toll-like receptor 4 (TLR4) is a pivotal PRR that induces cytokine production and bridges innate and adaptive immunity. Importantly, TLR4 recognizes various virus-derived pathogen-associated molecular patterns (PAMPs) and virus-induced damage-associated molecular patterns (DAMPs), usually leading to the activation of immune cells. However, the role of TLR4 in the humoral immune response induced by RABV has not been revealed yet. Based on TLR4-deficient ( TLR4 -/- ) and wild-type (WT) mouse models, we report that TLR4-dependent recruitment of the conventional type-2 dendritic cells (CD8α - CD11b + cDC2) into secondary lymph organs (SLOs) is critical for antigen presentation. cDC2-initiated differentiation of Tfh cells promotes the proliferation of germinal centre (GC) B cells, the formation of GCs, and the production of plasma cells (PCs), all of which contribute to the production of RABV-specific IgG and virus-neutralizing antibodies (VNAs). Collectively, our work demonstrates that TLR4 is necessary for the recruitment of cDC2 and for the induction of RABV-induced humoral immunity, which is regulated by the cDC2-Tfh-GC B axis. IMPORTANCE Vaccination is the most efficient method to prevent rabies. TLR4, a well-known immune sensor, plays a critical role in initiating innate immune response. Here, we found that TLR4 deficiency ( TLR4 -/- ) mice suppressed the induction of humoral immune response after immunization with rabies virus (RABV), including reduced production of VNAs and RABV-specific IgG, compared with that occurred in wild-type (WT) mice. As a consequence, TLR4 -/- mice exhibited higher mortality than WT mice after challenge with virulent RABV. Importantly, further investigation found that TLR4 signaling promoted the recruitment of cDC2 (CD8α + CD11b - ), a subset of cDCs known to induce CD4 + T cell immunity through their MHC-II presentation machinery. Our results imply that TLR4 is indispensable for an efficient humoral response to rabies vaccine, which provides new insight into the development of novel rabies vaccines.

scholarly journals COVID-ONE-hi: The One-stop Database for COVID-19 Specific Humoral Immunity and Clinical Parameters

2021 ◽  
Author(s):  
Zhaowei Xu ◽  
Yang Li ◽  
Qing Lei ◽  
Likun Huang ◽  
Dan-yun Lai ◽  
...  
Keyword(s):  
Humoral Immunity ◽  
Clinical Parameters ◽  
One Stop ◽  
The One

scholarly journals CD40L-deficient mice show deficits in antiviral immunity and have an impaired memory CD8+ CTL response.

1996 ◽  
Vol 183 (5) ◽  
pp. 2129-2142 ◽  
Author(s):  
P Borrow ◽  
A Tishon ◽  
S Lee ◽  
J Xu ◽  
I S Grewal ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Humoral Immunity ◽  
Cd4 T Cells ◽  
Antiviral Immunity ◽  
Ctl Response ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Deficient Mice

The ligand for CD40 (CD40L) is expressed on the surface of activated CD4+ T cells and its role in T-B cell collaborations and thymus-dependent humoral immunity is well established. Recently, by generating CD40L-knockout mice, we have confirmed its previously described role in humoral immunity and defined another important function of this molecule in the in vivo clonal expansion of antigen-specific CD4+ T cells. Here, we investigated the potential in vivo role of CD40L in antiviral immunity by examining the immune response mounted by CD40L-deficient mice following infection with lymphocytic choriomeningitis virus (LCMV), Pichinde virus, or vesicular stomatitis virus. Humoral immune responses of CD40L-deficient mice to these viruses were severely compromised, although moderate titres of antiviral IgM and some IgG2a were produced by virus-infected CD40L-deficient mice by a CD4+ T cell-independent mechanism. By contrast, CD40L-deficient mice made strong primary CTL responses to all three viruses. Interestingly however, although memory CTL activity was detectable in CD40L-deficient mice two months after infection with LCMV, the memory CTL response was much less efficient than in wild-type mice. Together, the results show that CD40-CD40L interactions are required for strong antiviral humoral immune responses, and reveal a novel role for CD40L in the establishment and/or maintenance of CD8+ CTL memory.

scholarly journals An International Epidemiology Study to Determine the Prevalence of Preexisting Cell-Mediated Immunity to Adeno-Associated Virus (AAV) in Adults with Severe Hemophilia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5794-5794
Author(s):  
Kavitha S. Rajavel ◽  
John C. Chapin ◽  
Ying Tang
Keyword(s):  
Immune Responses ◽  
Humoral Immunity ◽  
Hemophilia A ◽  
Peptide Pool ◽  
Cell Mediated Immunity ◽  
Severe Hemophilia ◽  
Adult Males ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Plasma Factor

Abstract Introduction: Adeno-associated virus (AAV) is a versatile gene therapy vector utilized widely in clinical gene transfer studies. AAV serotype 8 (AAV8) has been used successfully as a vector in liver-directed gene transfer in hemophilia clinical trials, and a recombinant AAV8 vector is used currently in Shire's BAX 888 clinical study (NCT03370172) for the treatment of patients with severe hemophilia A. However, 1 recognized limitation of intravenous administration of recombinant AAV is the barrier posed by preexisting immunity against AAV and the cross-reactivity of anti-AAV antibodies between various serotypes that results from natural exposure to the wild-type viruses. Neutralizing antibodies (NAbs) resulting from humoral immune responses can compromise vector transduction, and reactivation of memory T cells from cell-mediated immune responses can abrogate transgene expression and eliminate transduced cells. Understanding the prevalence of cell-mediated immune responses in the hemophilia population and the association between cell-mediated and humoral immunity is important in developing effective gene therapies. Objectives: To determine the prevalence of preexisting immunity towards AAV8 and AAV2 in the adult population of patients with hemophilia A and B, and to characterize the association between cell-mediated immunity and humoral immunity. Methods: In this ongoing study, peripheral blood samples were collected at outpatient visits from adult males (age 18-75 years) with severe hemophilia A (plasma factor VIII [FVIII] activity <1%) or hemophilia B (plasma factor IX [FIX] activity ≤2%) for determination of immunity towards AAV8 and AAV2. Patients could elect to participate in a single baseline visit or in the longitudinal study arm for up to 3 annual visits. Patients with inhibitors or a history of inhibitors to FVIII or FIX, an underlying lymphocyte disorder, or currently receiving cytotoxic chemotherapy, monoclonal antibodies, immunoglobulins, immunosuppression, or systemic antiviral therapy were excluded. The cell-mediated immune response against AAV8 peptide antigens was quantified using an interferon-γ enzyme-linked ImmunoSpot (ELISPOT) assay to determine the number of T cells responsive to 3 different pools of AAV8 capsid-specific protein fragments. Each AAV8 antigen pool consisted of 50-60 nonoverlapping peptides composed of 15 amino acid residues. Results were considered positive if the signal was >3 times above the background and >60 cells/million. Serum was collected for assessment of humoral immunity (AAV8 NAbs or AAV2 NAbs) using a cell-based transduction inhibition assay (titer cutoff: ≥1:5). Results: A total of 41 patients have enrolled in the study to date (mean ± SD age: 33.8 ± 11.1 years) and ELISPOT data are available for 37 patients. Of those with available data, 9/37 patients (24.3%) had a positive ELISPOT to ≥1 of the 3 AAV8 peptide pools tested. One patient tested positive for peptide pool 1, 3 for peptide pool 2, and 7 for peptide pool 3 (2 patients [5.6%] tested positive for both pools 2 and 3). Of the 9 patients with positive AAV8-specific ELISPOT results, 6 (66.7%) also had a positive result for AAV8 NAbs, while of 27 patients with negative ELISPOT results, 11 (40.7%) had a positive result for AAV8 NAbs. Conclusions: The results from this ongoing international epidemiology study demonstrate that the prevalence of preexisting cell-mediated immunity to AAV8 resulting from natural exposure to wild-type AAV is approximately 1 in 4 adult males with severe hemophilia A or B. Furthermore, there appears to be a correlation between cell-mediated and humoral immune responses, as two thirds of patients with positive AAV8-specific ELISPOT results also tested positive for AAV8 NAbs. Understanding the relationship between cell-mediated and humoral immunity and how it may affect an individual's response to AAV-based gene therapy will be key to successfully developing this novel therapy. Disclosures Rajavel: Shire: Employment, Equity Ownership. Chapin:Shire: Employment, Equity Ownership. Tang:Shire: Employment.

scholarly journals Igκ allelic inclusion is a consequence of receptor editing

2007 ◽  
Vol 204 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Rafael Casellas ◽  
Qingzhao Zhang ◽  
Nai-Ying Zheng ◽  
Melissa D. Mathias ◽  
Kenneth Smith ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Allelic Exclusion ◽  
Receptor Editing ◽  
Central Tolerance ◽  
Physiological Conditions ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
The One ◽  
Reactive Antibody

The discovery of lymphocytes bearing two light chains in mice carrying self-reactive antibody transgenes has challenged the “one lymphocyte–one antibody” rule. However, the extent and nature of allelically included cells in normal mice is unknown. We show that 10% of mature B cells coexpress both Igκ alleles. These cells are not the result of failure in allelic exclusion per se, but arise through receptor editing. We find that under physiological conditions, editing occurs both by deletion and by inclusion with equal probability. In addition, we demonstrate that B lymphocytes carrying two B-cell receptors are recruited to germinal center reactions, and thus fully participate in humoral immune responses. Our data measure the scope of allelic inclusion and provide a mechanism whereby autoreactive B cells might “escape” central tolerance.

Induction of humoral immunity in response to immunization with recombinantMycobacterium bovisBCG expressing the S1 subunit ofBordetella pertussistoxin

2005 ◽  
Vol 51 (12) ◽  
pp. 1015-1020 ◽  
Author(s):  
Marco A Medeiros ◽  
Geraldo R.G Armôa ◽  
Odir A Dellagostin ◽  
Douglas McIntosh
Keyword(s):  
Immune Responses ◽  
Pertussis Toxin ◽  
Whooping Cough ◽  
Low Cost ◽  
Long Term Memory ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Specific Igg

Two recombinant Mycobacterium bovis BCG (rBCG) vaccine strains were developed for the expression of cytoplasmically located S1 subunit of pertussis toxin, with expression driven by the hsp60 promoter of M. bovis (rBCG/pPB10) or the pAN promoter of Mycobacterium paratuberculosis (rBCG/pPB12). Both strains showed stable expression of equivalent levels of recombinant S1 in vitro and induced long-term (up to 8 months) humoral immune responses in BALB/c mice, although these responses differed quantitatively and qualitatively. Specifically, rBCG/pPB12 induced markedly higher levels of IgG1 than did rBCG/pPB10, and mice immunized with the former strain developed specific long-term memory to S1, as indicated by the production of high levels of S1-specific IgG in response to a sublethal challenge with pertussis toxin 15 months after initial immunization. When considered in combination with previous studies, our data encourage further evaluation of rBCG as a potential means of developing a low-cost whooping cough vaccine based on defined antigens.Key words: recombinant BCG, humoral immune response, B. pertussis.

Longitudinal humoral immune responses of Indian leaf monkey (Presbytis entellus) to Brugia malayi infection

Parasitology ◽  
1999 ◽  
Vol 119 (1) ◽  
pp. 53-60 ◽  
Author(s):  
P. K. MURTHY ◽  
K. TYAGI ◽  
R. P. GHOSH ◽  
P. S. R. MURTHY ◽  
R. K. CHATTERJEE
Keyword(s):  
Immune Responses ◽  
Brugia Malayi ◽  
Immunoblot Analysis ◽  
Presbytis Entellus ◽  
Disease Symptoms ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Latent Stage ◽  
Leaf Monkey ◽  
Specific Igg

Humoral immune responses of the Indian leaf monkey (Presbytis entellus) experimentally infected with Brugia malayi and exhibiting disease manifestations were studied. Microfilaraemia, filaria-specific IgG and circulating immune complexes (CICs) were determined in the monkeys at different time-points after inoculation of B. malayi 3rd-stage larvae. Sera were analysed for recognition pattern of adult parasite antigen molecules by immunoblotting. More than 60% of the infected monkeys developed episodic or persistent limb oedema with or without fever and with low or no microfilaraemia. While both CIC and filaria specific IgG levels were comparable in animals showing no disease symptoms (asymptomatics) and some animals showing symptoms (symptomatics), IgG levels peaked during pre-patent stage in symptomatics and during latent stage in asymptomatic animals. However, some of the symptomatic animals showed a low level of filaria-specific IgG as compared to asymptomatic and other symptomatic animals. The immunoblot analysis showed non-reactivity of 17 and 55 kDa antigens with sera of symptomatic animals. The results thus suggest that humoral immune responses as measured in the present study do not precede the development of the manifestations. However, 2 non-reactive antigen molecules identified by symptomatic sera need further study to establish their possible involvement, if any, in the development of acute disease manifestations in this model.

scholarly journals T Cell Mediated Antibody lnvariance in an Immune Response Against A Bacterial Carbohydrate Antigen Requires CD28/B7–1 Costimulation

2001 ◽  
Vol 8 (3-4) ◽  
pp. 243-257 ◽  
Author(s):  
André Rademaekers ◽  
Eckehart Kölsch ◽  
Christoph Specht
Keyword(s):  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
Clonal Expansion ◽  
Carbohydrate Antigen ◽  
Igg Antibodies ◽  
Humoral Immune ◽  
Specific Igg ◽  
The One ◽  
First Time

The humoral immune response againstα(1→3)dextran (Dex) in BALB/c mice is characterized by the formation of predominantly IgM antibodies bearing the J558 idiotype. IgG antibodies do not appear in euthymic mice. In athymic animals however, the response proceeds to a vigorous IgG production. In euthymic mice formation of IgG is suppressed by J558 idiotype- specific regulatory T cells recognizing in association with I-Edand in cognate T/B interaction the VH CDR3 derived peptide of the J558 idiotpye. Only B-2 lymphocytes produce IgG whereas B-1 cells do not participate in the production of this Ig class. Using a novel synthetic allα(1→3)-D-gluco configurated tetrasaccharide the Dex-specific B cells can for the first time be analyzed in FACS. In experiments using this newly designed low molecular Dex no signs of B cell apoptosis can be found. This demonstrates a true silencing of persisting Bγ memory cells and supports previous by adoptive transfer experiments. In this suppression an involvement of CD28/B7–1 interaction can be demonstrated which is a necessary costimulatory suppression signal in addition to the cognate TCR/peptide-I-Edinteraction between J558 Id-specific T cells and J558 idiotype beating B cells. This results in an activation of 178–4 Ts cells, leading to an overall suppression of the Dex-specific IgG isotype production on the one hand and on the other hand provides a signal for the survival and clonal expansion of J558 Id-positive B cells.

scholarly journals Combination of Protein and Viral Vaccines Induces Potent Cellular and Humoral Immune Responses and Enhanced Protection from Murine Malaria Challenge

2007 ◽  
Vol 75 (12) ◽  
pp. 5819-5826 ◽  
Author(s):  
Claire L. Hutchings ◽  
Ashley J. Birkett ◽  
Anne C. Moore ◽  
Adrian V. S. Hill
Keyword(s):  
Immune Responses ◽  
Humoral Immunity ◽  
Viral Vector ◽  
Core Antigen ◽  
Protein Vaccine ◽  
Humoral Immune ◽  
Cell Immunity ◽  
Viral Vaccines ◽  
Cellular And Humoral Immunity ◽  
Hepatitis B Core Antigen

ABSTRACT The search for an efficacious vaccine against malaria is ongoing, and it is now widely believed that to confer protection a vaccine must induce very strong cellular and humoral immunity concurrently. We studied the immune response in mice immunized with the recombinant viral vaccines fowlpox strain FP9 and modified virus Ankara (MVA), a protein vaccine (CV-1866), or a combination of the two; all vaccines express parts of the same preerythrocytic malaria antigen, the Plasmodium berghei circumsporozoite protein (CSP). Mice were then challenged with P. berghei sporozoites to determine the protective efficacies of different vaccine regimens. Two immunizations with the protein vaccine CV-1866, based on the hepatitis B core antigen particle, induced strong humoral immunity to the repeat region of CSP that was weakly protective against sporozoite challenge. Prime-boost with the viral vector vaccines, FP9 followed by MVA, induced strong T-cell immunity to the CD8+ epitope Pb9 and partially protected animals from challenge. Physically mixing CV-1866 with FP9 or MVA and then immunizing with the resultant combinations in a prime-boost regimen induced both cellular and humoral immunity and afforded substantially higher levels of protection (combination, 90%) than either vaccine alone (CV-1866, 12%; FP9/MVA, 37%). For diseases such as malaria in which different potent immune responses are required to protect against different stages, using combinations of partially effective vaccines may offer a more rapid route to achieving deployable levels of efficacy than individual vaccine strategies.

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