scholarly journals Early cross-coronavirus reactive signatures of protective humoral immunity against COVID-19

2021 ◽  
Author(s):  
Paulina Kaplonek ◽  
Chuangqi Wang ◽  
Yannic Bartsch ◽  
Stephanie Fischinger ◽  
Matthew J Gorman ◽  
...  
Keyword(s):  
Immune Response ◽  
Early Development ◽  
Humoral Immunity ◽  
Specific Antibody ◽  
Large Cohort ◽  
Specific Immune Response ◽  
Correlate Of Protection ◽  
Humoral Immune ◽  
Specific Immunity ◽  
The World

The introduction of vaccines has inspired new hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against COVID-19, thus we profiled the earliest humoral signatures in a large cohort of severe and asymptomatic COVID-19 individuals. While a SARS-CoV-2-specific immune response evolved rapidly in survivors of COVID-19, non-survivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibody evolution. Given the conservation of S2 across β-coronaviruses, we found the early development of SARS-CoV-2-specific immunity occurred in tandem with pre-existing common β-coronavirus OC43 humoral immunity in survivors, which was selectively also expanded in individuals that develop paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.

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 Anti–4-1bb Monoclonal Antibodies Abrogate T Cell–Dependent Humoral Immune Responses in Vivo through the Induction of Helper T Cell Anergy

1999 ◽  
Vol 190 (10) ◽  
pp. 1535-1540 ◽  
Author(s):  
Robert S. Mittler ◽  
Tina S. Bailey ◽  
Kerry Klussman ◽  
Mark D. Trailsmith ◽  
Michael K. Hoffmann
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cells ◽  
Humoral Immunity ◽  
Cd8 T Cells ◽  
Immunodeficient Mice ◽  
Humoral Immune

The 4-1BB receptor (CDw137), a member of the tumor necrosis factor receptor superfamily, has been shown to costimulate the activation of T cells. Here we show that anti–mouse 4-1BB monoclonal antibodies (mAbs) inhibit thymus-dependent antibody production by B cells. Injection of anti–4-1BB mAbs into mice being immunized with cellular or soluble protein antigens induced long-term anergy of antigen-specific T cells. The immune response to the type II T cell–independent antigen trinintrophenol-conjugated Ficoll, however, was not suppressed. Inhibition of humoral immunity occurred only when anti–4-1BB mAb was given within 1 wk after immunization. Anti–4-1BB inhibition was observed in mice lacking functional CD8+ T cells, indicating that CD8+ T cells were not required for the induction of anergy. Analysis of the requirements for the anti–4-1BB–mediated inhibition of humoral immunity revealed that suppression could not be adoptively transferred with T cells from anti–4-1BB–treated mice. Transfer of BALB/c splenic T cells from sheep red blood cell (SRBC)-immunized and anti–4-1BB–treated mice together with normal BALB/c B cells into C.B-17 severe combined immunodeficient mice failed to generate an anti-SRBC response. However, B cells from the SRBC-immunized, anti–4-1BB–treated BALB/c mice, together with normal naive T cells, exhibited a normal humoral immune response against SRBC after transfer, demonstrating that SRBC-specific B cells were left unaffected by anti–4-1BB mAbs.

Diet quality affects postnuptial molting and feather quality of the house sparrow (Passer domesticus): interaction with humoral immune function?

2008 ◽  
Vol 86 (8) ◽  
pp. 834-842 ◽  
Author(s):  
Péter László Pap ◽  
Csongor István Vágási ◽  
Gábor Árpád Czirják ◽  
Zoltán Barta
Keyword(s):  
Immune Response ◽  
Body Mass ◽  
Humoral Immunity ◽  
Immune Activation ◽  
Passer Domesticus ◽  
The Body ◽  
House Sparrows ◽  
Humoral Immune ◽  
Quality Food

We investigated the effects of nutritional limitation, humoral immune activation, and their interaction on postnuptial molting of aviary-kept house sparrows ( Passer domesticus (L., 1758)). In a 2 × 2 experimental design, we measured the progress of molting and the quality of feathers produced during molting by house sparrows exposed to different diet qualities (high and low) and humoral immune activation with sheep red blood cells (SRBC). Food quality, but not the activation of humoral immunity, affected significantly the body mass and the process of molting. Sparrows feeding on low-quality food had decreased body mass and longer molts than the high-quality group. Low-quality food, but not the activation of humoral immunity, reduced significantly the length and mass (i.e., the quality) of primaries grown during molting. Birds responded significantly to injection with SRBC compared with the control group, but the immune response was similar between nutritional groups. The absence of a negative effect of humoral immunity on molting in house sparrows might be related to the low energy and nutritional requirements of mounting and maintaining a humoral immune response.

scholarly journals The time course of the humoral immune response to rhinovirus infection

1989 ◽  
Vol 103 (3) ◽  
pp. 659-669 ◽  
Author(s):  
W. S. Barclay ◽  
W. Al-Nakib ◽  
P. G. Higgins ◽  
D. A. J. Tyrrell
Keyword(s):  
Immune Response ◽  
Specific Antibody ◽  
Humoral Immune Response ◽  
Time Course ◽  
Human Rhinovirus ◽  
Specific Antibodies ◽  
Humoral Immune ◽  
Rhinovirus Infection ◽  
Nasal Secretions

SUMMARYThe specific humoral immune response of 17 volunteers to infection with human rhinovirus type 2 (HRV-2) has been measured both by neutralization and by ELISA. Six volunteers who had HRV-2-specific antibodies in either serum or nasal secretions before HRV-2 inoculation were resistant to infection and illness. Of the remaining 11 volunteers who had little pre-existing HRV-2-specific antibody, one was immune but 10 became infected and displayed increases in HRV-2-specific antibodies. These antibodies first increased 1–2 weeks after infection and reached a maximum at 5 weeks. All six resistant volunteers who had high pre-existing antibody and eight of the volunteers who became infected maintained their HRV-2-specific antibody for at least 1 year. At this time they were protected against reinfection. Two volunteers showed decreases in HRV-2-specific antibodies from either serum or nasal secretions. They became infected but not ill after HRV-2 inoculation 1 year later.

scholarly journals Characteristics of immune response to protozoan infections

2003 ◽  
Vol 56 (11-12) ◽  
pp. 557-563 ◽  
Author(s):  
Valentina Arsic-Arsenijevic ◽  
Aleksandar Dzamic ◽  
Sanja Mitrovic ◽  
Ivana Radonjic ◽  
Ivana Kranjcic-Zec
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
T Cell Activation ◽  
Defense Mechanisms ◽  
Cell Activation ◽  
Blood Stream ◽  
Biochemical Properties ◽  
Natural Immunity ◽  
Humoral Immune ◽  
Specific Immunity

Introduction When protozoa enter the blood stream or tissues they can often survive and replicate because they adapt to the resisting natural host defenses. The interaction of immune system with infectious organisms is a dynamic interplay of host mechanisms aimed at eliminating infections and microbial strategies designed to permit survival in the face of powerful effectors mechanisms. Protozoa cause chronic and persistent infections, because natural immunity against them is weak and because protozoa have evolved multiple mechanisms for evading and resisting specific immunity. Natural and specific immune response to protozoa Different protozoa vary greatly in their structural and biochemical properties and stimulate distinct patterns of immune responses and have evolved unique mechanisms for evading specific immunity. Protozoa activate quite distinct specific immune responses, which are different from the responses to fungi, bacteria and viruses. Protozoa may be phagocytozed by macrophages, but many are resistant to phagocytic killing and may even replicate within macrophages. T. brucei gambiense is the best example of protozoa which can induce humoral immune response because of its extra-cellular location. In Leishmania sp. infections, cellular defense mechanisms depend upon CD4+ T-lymphocytes and activate macrophages as effectors cells that are regulated by cytokines of Th1 subset. Plasmodium sp. is a protozoa which show the diversity of defence mechanisms which can be cellular or humoral, depending on Ag and protozoa's location. Immune evasion mechanisms of protozoa Different protozoa have developed remarkably effective ways of resisting specific immunity: a) anatomic sequestration is commonly observed with protozoa Plasmodium and T. gondii; b) some protozoa can become resistant to immune effectors mechanisms: Trypanosoma, Leishmania and T. gondii; c) some protozoa have developed effective mechanisms for varying their surface antigens: Plasmodium and Trypanosoma; d) some protozoa shed their antigen coats, either spontaneously or after binding with specific antibodies: E. histolytica; e) some protozoa alter host immune response by nonspecific and generalized immunosuppression (abnormalities in cytokine production, deficient T cell activation): Trypanosoma, Leishmania, Toxoplasma, Entamoeba. Conclusion Protozoa activate numerous, different immune mechanisms in human body. Evolution, progression and outcome of diseases depend upon these mechanisms. Resent progresses in research have defined and selected Ag as candidates for new vaccines. Better definitions regarding the role of cytokines in protozoaninfections will facilitate rational development of cytokines and cytokine antagonists and their use as immunotherapeutic agents.

scholarly journals Elotuzumab Enhances the Th2-Mediated Immune Response of Dendritic Cell Induced By Immunomodulatory Drugs (IMiDs)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4342-4342
Author(s):  
Yoshiko Azuma ◽  
Tomoki Ito ◽  
Muneo Inaba ◽  
Kai Imai ◽  
Masaaki Hotta ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Dendritic Cell ◽  
Humoral Immunity ◽  
Immune Status ◽  
Fold Increase ◽  
Immune Dysfunction ◽  
Th2 Response ◽  
Humoral Immune ◽  
Before And After

Background: Elotuzumab, a humanized IgG1 monoclonal antibody targeting SLAMF7, is useful for the treatment of Relapsed or Refractory multiple myeloma (RRMM) in combination with Lenalidomide (LEN). However, cellular and molecular mechanisms underlying the immunomodulatory effects of elotuzumab still remain largely unclear. We have previously reported that LEN displays immunopotentiating activity that enhances Th2-mediated response at dendritic cell (DC) phase as upstream immune cascade associated with humoral immunity. DCs are pivotal cells in the sense of orchestrating both cell-mediated (linking with Th1) and humoral (linking with Th2) immunity as masters of the immune system. Series of analyses have clarified myeloid DCs (mDCs) play an important role in allergic immune response by the induction of Th2 response. Here, we focused on the effects of elotuzumab in combination with LEN on the function of human mDCs. Methods: Purified blood human CD11+ mDCs from healthy adult volunteers using cell sorting were cultured and analyzed by flow cytometry and ELISA. Serum were obtained from 16 MM patients with before and after elotuzumab therapy. This study was approved by the Institutional Review Board of Kansai Medical University. Results: We found that surface expression of SLAMF7 on mDCs was upregulated in response to Th2-inducing cytokine, thymic stromal lymphopoietin (TSLP) and the expression level was higher in response to TSLP than in response to toll-like receptor ligand R848. Elotuzumab at clinical in vivo plasma concentration of 30 to 300 µg/ml did not affect mDC survival and their CD86 and OX40-ligand expression when stimulated with 0.3 µM LEN and/or TSLP for 24 h. LEN enhanced TSLP-mediated Th2-recruiting chemokine CCL17/TARC from mDCs which functions as chemoattractant for memory Th2 cells and contribute to allergy and humoral immune responses, and elotuzumab significantly enhanced the LEN-mediated production of CCL17/TARC (TSLP+LEN as control vs. TSLP+LEN+100 µg/ml elotuzumab; 1.23 fold increase: p=0.003, and control vs. TSLP+LEN+300 µg/ml elotuzumab; 1.38 fold increase: p=0.038). This finding suggest elotuzumab enhances Th2-mediated immune profile at upstream phase of humoral immunity. In addition, serum CCL17 levels were analyzed in RRMM patients before and after 3 cycle elotuzumab administration (n=16). We found, serum CCL17 levels after elotuzumab administration were significantly higher compared with those before elotuzumab treatment (after; 1512 ± 459 pg/ml vs. before; 402.2 ± 87.4 pg/ml: p = 0.013). Conclusion: MM involves an element of humoral immune dysfunction. Immune status is important for the prognosis of MM, and clinical outcome can be improved by the recovery of immune status. In this context, our data showing the enhancement of Th2-mediated response by elotuzumab provide a plausible explanation for the observed clinical benefit of this antibody-drug in MM. This function of elotuzumab seems to be relevant to the treatment of MM patients under humoral immune dysfunction. Based on our data in focusing on DCs in the immune system, elotuzumab and IMiDs could function as immunostimulators of humoral immunity via mDCs, and this finding elucidated an additional cellular target of elotuzumab. Disclosures Ito: Celgene: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding.

scholarly journals A crucial role for Jagunal homolog 1 in humoral immunity and antibody glycosylation in mice and humans

2020 ◽  
Vol 218 (1) ◽  
Author(s):  
Astrid Hagelkruys ◽  
Gerald Wirnsberger ◽  
Johannes Stadlmann ◽  
Miriam Wöhner ◽  
Marion Horrer ◽  
...  
Keyword(s):  
Immune Response ◽  
Endoplasmic Reticulum ◽  
B Cells ◽  
Er Stress ◽  
Rare Disease ◽  
Humoral Immunity ◽  
Viral Infections ◽  
Loss Of Function ◽  
Humoral Immune ◽  
Specific Antigens

Jagunal homolog 1 (JAGN1) has been identified as a critical regulator of neutrophil biology in mutant mice and rare-disease patients carrying JAGN1 mutations. Here, we report that Jagn1 deficiency results in alterations in the endoplasmic reticulum (ER) of antibody-producing cells as well as decreased antibody production and secretion. Consequently, mice lacking Jagn1 in B cells exhibit reduced serum immunoglobulin (Ig) levels at steady state and fail to mount an efficient humoral immune response upon immunization with specific antigens or when challenged with viral infections. We also demonstrate that Jagn1 deficiency in B cells results in aberrant IgG N-glycosylation leading to enhanced Fc receptor binding. Jagn1 deficiency in particular affects fucosylation of IgG subtypes in mice as well as rare-disease patients with loss-of-function mutations in JAGN1. Moreover, we show that ER stress affects antibody glycosylation. Our data uncover a novel and key role for JAGN1 and ER stress in antibody glycosylation and humoral immunity in mice and humans.

Sporopollenin Spikes Augment Antigen‐Specific Immune Response and Generate Long‐Lived Humoral Immunity

2020 ◽  
Vol 3 (10) ◽  
pp. 2000102 ◽  
Author(s):  
Md Jasim Uddin ◽  
Pedro Gonzalez‐Cruz ◽  
Juliusz Warzywoda ◽  
Harvinder Singh Gill
Keyword(s):  
Immune Response ◽  
Humoral Immunity ◽  
Specific Immune Response

Antigen-specific immunity and tumor inflammation after vaccination with BPX-101, a drug-activated dendritic cell vaccine for metastatic castration-resistant prostate cancer (mCRPC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 176-176
Author(s):  
T. M. Wheeler ◽  
B. Zhao ◽  
G. Sonpavde ◽  
J. D. McMannis ◽  
Y. Bai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
T Cells ◽  
Injection Site ◽  
Specific Immune Response ◽  
Cell Vaccine ◽  
Cancer Tissue ◽  
Specific Immunity ◽  
Dc Vaccine ◽  
Prostate Cancer Tissue

176 Background: We report evidence of antigen-specific immunity and severe prostate cancer inflammation and necrosis after vaccination in patients enrolled in a phase I-IIa clinical trial of BPX-101, a drug-activated DC vaccine for mCRPC. Methods: Twelve men with progressive, mCRPC were enrolled in a 3+3 dose escalation trial evaluating BPX-101 and activating agent AP1903. BPX-101, which targets prostate-specific membrane antigen (PSMA), was administered intradermally every 2 weeks for 6 doses, followed 24 hours after each dose by infusion of AP1903 (0.4 mg/kg). Injection site skin biopsies were performed after the fourth vaccination. T cells cultured from the skin biopsy ex vivo were stimulated with PSMA protein or control antigens, and were analyzed using Luminex microspheres for 30 inflammatory cytokines/chemokines. One patient (#1007) with an intact prostate developed lower urinary tract bleeding after the fifth vaccination and underwent a transurethral resection of bleeding prostate cancer tissue. Paraffin-embedded blocks were stained for hematoxylin and eosin (H&E). Immunohistochemical stains for CD3, CD4, CD8 and CD34 were also performed. Results: Of 5 subjects with evaluable injection site biopsy results, all exhibited PSMA-specific immunity (3 TH1-biased and 2 TH2- biased). Subject 1007's injection site biopsy demonstrated a significant >10-fold increase in IFN-gamma and IL-2 after stimulation by PSMA, compared to stimulation by ovalbumin, consistent with induction of a strong PSMA-specific CTL or TH1-biased immune response. H&E stained resected prostate tissue demonstrated Gleason 8 (4+4) prostate adenocarcinoma exhibiting a severe inflammatory response, consisting of infiltrating plasma cells and CD4+ and CD8+ T cells. Large areas of necrosis were seen adjacent to inflamed prostate cancer tissue. Conclusions: Vaccination with BPX-101 followed by AP1903 can induce a strong, PSMA-specific immune response. Furthermore, evidence of severe prostate cancer-specific inflammation and necrosis, associated with a strong PSMA-specific immune response has been observed after multiple doses of BPX-101. [Table: see text]

scholarly journals Proteases secreted by Gnathostoma binucleatum degrade fibronectin and antibodies from mammals

2015 ◽  
Vol 52 (1) ◽  
pp. 6-10 ◽  
Author(s):  
N. Vibanco-Pérez ◽  
M. De J. Durán-Avelar ◽  
J. F. Zambrano-Zaragoza ◽  
G. H. Ventura-Ramón
Keyword(s):  
Immune Response ◽  
Endemic Species ◽  
Humoral Immune Response ◽  
Host Tissue ◽  
Molecular Weights ◽  
Humoral Immune ◽  
Third Stage ◽  
The World ◽  
Human Fibronectin ◽  
Secretory Products

Summary Gnathostomiasis is a prevalent zoonosis in humans in some regions of the world. The genus Gnathostoma is considered an accidental parasite for humans; G. binucleatum is the endemic species in Nayarit, Mexico. This work was designed to determine the proteolytic activity of the excretory-secretory products (ESP) of advanced third-stage larvae (ADVL3) of Gnathostoma binucleatum against human fibronectin and antibodies from human and sheep. Our findings showed protease activity against human fibronectin as well as sheep and human gamma globulins of the ESP at molecular weights of 80 and 56 kDa. The proteases found in the ESP of G. binucleatum are thus candidate molecules for consideration as pathogenic elements, owing to the fact that they destroy proteins of the host tissue, which probably allows them to migrate through those tissues and degrade molecules involved in the humoral immune response.

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