scholarly journals Sustained antibody response to ZIKV infection induced by NS1 protein is accompanied by the progressive appearance of autoreactive antibodies and cross-reactive B cell clones

2020 ◽  
Author(s):  
Cecilia B. Cavazzoni ◽  
Vicente B. T. Bozza ◽  
Lucas Tostes ◽  
Bruno Maia ◽  
Luka Mesin ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Zika Virus ◽  
Cross Reactivity ◽  
Ns1 Protein ◽  
Structural Protein ◽  
Humoral Immune ◽  
Autoreactive Antibodies ◽  
Cell Clones

AbstractAntibodies are key players in controlling viral infections. However, in addition to antigen-specific responses to viral antigens, humoral immune response can generate polyreactive and autoreactive antibodies of unknown function. Dengue and Zika virus infections have been linked to autoimmune disorders including Guillain-Barrè syndrome. A unique feature of flaviviruses is the secretion of non-structural protein 1 (NS1) by infected cells. NS1 is highly immunogenic and antibodies targeting NS1 can have both protective and pathogenic roles. In the present study, we investigated the humoral immune response to Zika virus NS1 and found NS1 to be an immunodominant viral antigen correlated to the presence of autoreactive antibodies. Through single B cell cultures, we coupled binding assays and BCR sequencing, confirming the immunodominance of NS1 and the presence of self-reactive clones in germinal centers both after infection and immunization, some of which were cross-reactivity with NS1. Anti-NS1 B cell clones showed features related to pathogenic autoreactive antibodies. Our findings demonstrate NS1 immunodominance at the cellular level as well as a potential role for NS1 in ZIKV associated autoimmune manifestations.

scholarly journals The immunodominant antibody response to Zika virus NS1 protein is characterized by cross-reactivity to self

2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Cecilia B. Cavazzoni ◽  
Vicente B.T. Bozza ◽  
Tostes C.V. Lucas ◽  
Luciana Conde ◽  
Bruno Maia ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Zika Virus ◽  
Nonstructural Protein ◽  
Cross Reactivity ◽  
Ns1 Protein ◽  
Humoral Immune ◽  
Nonstructural Protein 1 ◽  
Autoreactive Antibodies

Besides antigen-specific responses to viral antigens, humoral immune response in virus infection can generate polyreactive and autoreactive antibodies. Dengue and Zika virus infections have been linked to antibody-mediated autoimmune disorders, including Guillain-Barré syndrome. A unique feature of flaviviruses is the secretion of nonstructural protein 1 (NS1) by infected cells. NS1 is highly immunogenic, and antibodies targeting NS1 can have both protective and pathogenic roles. In the present study, we investigated the humoral immune response to Zika virus NS1 and found NS1 to be an immunodominant viral antigen associated with the presence of autoreactive antibodies. Through single B cell cultures, we coupled binding assays and BCR sequencing, confirming the immunodominance of NS1. We demonstrate the presence of self-reactive clones in germinal centers after both infection and immunization, some of which present cross-reactivity with NS1. Sequence analysis of anti-NS1 B cell clones showed sequence features associated with pathogenic autoreactive antibodies. Our findings demonstrate NS1 immunodominance at the cellular level as well as a potential role for NS1 in ZIKV-associated autoimmune manifestations.

scholarly journals Immunogenicity of Recombinant DNA Vaccine Encoding Non-Structural Protein-1 Dengue Virus Serotype-2 in Balb/c Mice

2021 ◽  
Vol 15 (2) ◽  
pp. 4
Author(s):  
Elitha Pulungan
Keyword(s):  
Immune Response ◽  
Dengue Virus ◽  
Dna Vaccine ◽  
Humoral Immune Response ◽  
Structural Proteins ◽  
Ns1 Protein ◽  
Structural Protein ◽  
Humoral Immune ◽  
Virus Serotype ◽  
Positive Strand Rna

Background: Dengue Hemorrhagic Fever (DHF) is an infectious disease caused by the dengue virus (DENV) which spread widely in tropical and subtropical regions of the world. DENV is a single-positive strand RNA virus with a genome size of ± 11kb which encodes three structural proteins, seven non-structural proteins, and two untranslated regions (UTR). The non-structural protein-1 (NS1) of DENV is known to have important role in dengue pathogenesis also promising to be developed as dengue vaccine. Lately, novel vaccine approach by DNA immunization have given new perspective for a safe, stable, and immunogenic vaccine platform. Previously, we have successfully construct DNA vaccine encoding NS1 protein of DENV2 (pUNS1) which express recombinant NS1 protein in-vitro. Thus, in this current study the ability of pUNS1 to induce humoral immune response will be further analyzed by in mice immunization. Methods: Sixteen BALB/c mice aged of 4 weeks were immunized 3 times with 100 µg of pUNS1 or pUMVC4a on 2 week time interval. Blood sampling was carried out just before immunization and termination was done 2 week after last immunization. Titer from individual mice sera against DENV-2 were measure with in-house ELISA. Results: IgG against NS1 protein of DENV2 titer from mice group immunized with recombinant pUNS1 shown high ELISA absorbancies, 5 times higher than pUMVC4a group. This result suggest the ability of pUNS1 to induce humoral immune response against NS1 DENV-2 in-vivo. Conclusion: Recombinant pUNS1 can induce humoral immune response in mice.

scholarly journals Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites: Naturally Acquired Humoral Immune Response and B-Cell Epitope Mapping in Brazilian Amazon Inhabitants

2017 ◽  
Vol 8 ◽  
Author(s):  
Rodrigo Nunes Rodrigues-da-Silva ◽  
Isabela Ferreira Soares ◽  
Cesar Lopez-Camacho ◽  
João Hermínio Martins da Silva ◽  
Daiana de Souza Perce-da-Silva ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Plasmodium Vivax ◽  
Humoral Immune Response ◽  
Epitope Mapping ◽  
Cell Epitope ◽  
Brazilian Amazon ◽  
Humoral Immune ◽  
B Cell Epitope

scholarly journals Babesia bovis RON2 contains conserved B-cell epitopes that induce an invasion-blocking humoral immune response in immunized cattle

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Mario Hidalgo-Ruiz ◽  
Carlos E. Suarez ◽  
Miguel A. Mercado-Uriostegui ◽  
Ruben Hernandez-Ortiz ◽  
Juan Alberto Ramos ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Babesia Bovis ◽  
B Cell Epitopes ◽  
Humoral Immune

B Cell-Related Chemokine (CXCL13) in CSF is Correlated with the Intrathecal Humoral Immune Response in Patients with Multiple Sclerosis

2020 ◽  
Vol 37 ◽  
pp. 101569
Author(s):  
Sawsan Feki ◽  
Mariem Dammak ◽  
Sabrina Mejdoub ◽  
Saba Gargouri ◽  
Salma Sakka ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Humoral Immune

Vav-2 signalling participates in the humoral immune response and B cell maturation

2001 ◽  
Vol 29 (5) ◽  
pp. A129-A129
Author(s):  
G. Doody ◽  
S. Bell ◽  
E. Vigorito ◽  
E. Clayton ◽  
S. McAdam ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Cell Maturation ◽  
Humoral Immune ◽  
B Cell Maturation

A New Vaccine Paradigm To Break Tolerance with Potential Applications for the Immunotherapy of B Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1411-1411
Author(s):  
Ronald P. Taylor ◽  
Emily C. Whipple ◽  
Margaret A. Lindorfer ◽  
Andrew H. Ditto ◽  
Ryan S. Shanahan
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
B Cells ◽  
B Cell ◽  
Humoral Immune Response ◽  
Critical Role ◽  
B Cell Lymphoma ◽  
Breakdown Product ◽  
Humoral Immune ◽  
Mouse Igg2a

Abstract Complement (C) plays a critical role in the immune response by opsonizing immune complexes (IC) and thymus-independent type 2 antigens with C3 breakdown product C3dg. We investigated the in vivo fate and handling in mice of anti-CR1/CR2 mAb 7G6. We used this rat IgG mAb as a surrogate for C3dg-opsonized IC; mAb 7G6 binds to CR1/CR2 with high affinity, blocks C3dg binding and saturates mouse B cell CR2 at inputs of only 2 ug. RIA, flow cytometry, and fluorescence immunohistochemistry were used to examine the disposition of 0.5–2 ug quantities of mAb 7G6 infused i.v. in mice. The mAb binds to circulating B cells and in the spleen binds preferentially to marginal zone (MZ) B cells. However, within 24 h MZ B cells relocate and transfer the mAb to regions rich in follicular dendritic cells (FDC). Localization of intact antigen to FDC should induce a substantial immune response, and therefore we immunized mice and monkeys i.v. with low doses (1–20 ug/kg) of prototype antigens constructed with anti-CR1/2 mAb 7G6 or anti-CR2 mAb HB135, respectively. We observed a strong immune response characterized by early development of IgG antibodies and long-lasting immunity extending out to at least one year. We applied our immunization paradigm to mouse IgG idiotypes, based on i.v. infusion of mouse IgG2a mAbs which were cross-linked with mAb 7G6. The purpose of these experiments was to determine if tolerance can be broken in order to develop a more powerful vaccine strategy to induce a cytotoxic humoral immune response to malignant B cells based on targeting the idiotype of immunoglobulin molecules expressed on their surfaces. I.V. immunization with the constructs indeed generated a mouse IgG1 immune response to two different mouse IgG2a mAbs, as demonstrated by ELISA. The immune response was idiotype specific, but some anti-isotype antibodies were also detected. Moreover, sera from immunized mice immunoprecipitated the specific radiolabeled mouse mAbs in the presence of 7.5% polyethylene glycol. This humoral immune response was also demonstrable in flow cytometry assays in which IgG1 in sera of immunized mice bound to erythrocytes opsonized with bispecific mAb constructs consisting of the IgG2a mAb crosslinked with an anti-CR1 mAb. The present approach, based on coupling the targeted immunoglobulin to an anti-CR2 mAb for delivery to FDC, may lead to a more effective immunotherapeutic vaccine compared to methods currently in clinical trials which require use of glutaraldehyde to effect crosslinking of the targeted immunoglobulin to KLH.

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