scholarly journals Low‐affinity but high‐avidity interactions may offer an explanation forIgE‐mediated allergen‐cross‐reactivity

Allergy ◽  
2021 ◽  
Author(s):  
Xinyue Chang ◽  
Lisha Zha ◽  
Alexandra Wallimann ◽  
Mona O. Mohsen ◽  
Pascal Krenger ◽  
...  
Keyword(s):  
Cross Reactivity ◽  
High Avidity

scholarly journals New strategy to select cross-reactivity Meningococci strains: immunization with Outer membrane vesicles of serogroup C and cationic lipid as adjuvant

2021 ◽  
Author(s):  
Amanda Izeli Portilho ◽  
Gabriela Trzewikowski de Lima ◽  
Elizabeth De Gaspari
Keyword(s):  
Outer Membrane ◽  
Public Health Problem ◽  
Cationic Lipid ◽  
Humoral Response ◽  
Membrane Vesicles ◽  
Cross Reactivity ◽  
Outer Membrane Vesicles ◽  
High Avidity ◽  
Avidity Index ◽  
High Avidity Index

Background: Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, is a public health problem, associated with high levels of morbidity and mortality, capable of causing outbreaks or epidemics, but preventable through vaccination. In Brazil, the main serogroups isolated are C and B. The last epidemic occurred in the 80s, in Sao Paulo, because of a B:4:P1.15 strain. Methods: Adult Swiss mice were immunized with outer membrane vesicles (OMV) of N. meningitidis strain C:4:P1.15, adjuvanted by the cationic lipid dioctadecyldimethylammonium bromide in bilayer fragments (DDA-BF), administered via prime-booster (intranasal/subcutaneous) scheme. The humoral response was accessed by Immunoblotting and ELISA, using homologous immunization strain and a different serogroup but equal serosubtype strain, N. meningitidis B:4:P1.15. Results: Immunoblotting revealed the recognition of antigens associated with the molecular weight of Porin A and Opacity proteins, which are immunogenic but highly heterogeneous, and Tbp and NspA, which are more homogeneous between meningococci strains. ELISA results showed antibody production that persisted after 190 days and recognized the C:4:P1.15 and the B:4:P1.15 strains, with high avidity index. The adjuvanted group recognized antigens following the IN prime and had a higher avidity index against the heterologous strain. Conclusions: DDA-BF improved the humoral response, but the OMV alone induced high avidity index antibodies as well. Even though these are preliminary results, we see it as a promising approach for affordable meningococcal immunization in developing countries, at outbreak or epidemic situations.

scholarly journals Immunological Cross-Reactivity of an Ancestral and the Most Recent Pandemic Norovirus GII.4 Variant

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 91 ◽  
Author(s):  
Kirsi Tamminen ◽  
Maria Malm ◽  
Timo Vesikari ◽  
Vesna Blazevic
Keyword(s):  
Antigenic Variation ◽  
Neutralization Assay ◽  
Cross Reactivity ◽  
High Avidity ◽  
Virus Like Particle ◽  
Blocking Activity ◽  
Ifn Γ ◽  
Pandemic Strains ◽  
Norovirus Gii ◽  
Antigen Presenting

Norovirus (NoV) genotype GII.4 is responsible for the majority of NoV infections causing pandemics every few years. A NoV virus-like particle (VLP)-based vaccine should optimally cover the high antigenic variation within the GII.4 genotype. We compared the immune responses generated by VLPs of the ancestral GII.4 1999 strain (GII.4 1995/96 US variant) and the most recent GII.4 Sydney 2012 pandemic strains in mice. No significant differences were observed in the type-specific responses but GII.4 1999 VLPs were more potent in inducing high-avidity antibodies with better cross-reactivity. GII.4 1999 immune sera blocked binding of GII.4 2006 and GII.4 2012 VLPs to the putative receptors in a surrogate neutralization assay, whereas GII.4 2012 immune sera only had low blocking activity against GII.4 2006 VLPs. Amino acid substitution in the NERK motif (amino acids 310, 316, 484, and 493, respectively), altering the access to conserved blocking epitope F, moderately improved the cross-blocking responses against mutated GII.4 2012 VLPs (D310N). NoV GII.4 1999 VLPs, uptaken and processed by antigen-presenting cells, induced stronger interferon gamma (IFN-γ) production from mice splenocytes than GII.4 2012 VLPs. These results support the use of GII.4 1999 VLPs as a major component of a NoV vaccine.

scholarly journals From Anti-SARS-CoV-2 Immune Response to the Cytokine Storm via Molecular Mimicry

Antibodies ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 36
Author(s):  
Darja Kanduc
Keyword(s):  
Macrophage Activation ◽  
Molecular Mimicry ◽  
Cross Reactivity ◽  
High Avidity ◽  
Cytokine Storm ◽  
Potential Mechanism ◽  
Human Proteins ◽  
Inflammatory Proteins ◽  
Anti Inflammatory

The aim of this study was to investigate the role of molecular mimicry in the cytokine storms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human proteins endowed with anti-inflammatory activity were assembled and analyzed for peptide sharing with the SARS-CoV-2 spike glycoprotein (gp) using public databases. It was found that the SARS-CoV-2 spike gp shares numerous pentapeptides with anti-inflammatory proteins that, when altered, can lead to cytokine storms characterized by diverse disorders such as systemic multiorgan hyperinflammation, macrophage activation syndrome, ferritinemia, endothelial dysfunction, and acute respiratory syndrome. Immunologically, many shared peptides are part of experimentally validated epitopes and are also present in pathogens to which individuals may have been exposed following infections or vaccinal routes and of which the immune system has stored memory. Such an immunologic imprint might trigger powerful anamnestic secondary cross-reactive responses, thus explaining the raging of the cytokine storm that can occur following exposure to SARS-CoV-2. In conclusion, the results support molecular mimicry and the consequent cross-reactivity as a potential mechanism in SARS-CoV-2-induced cytokine storms, and highlight the role of immunological imprinting in determining high-affinity, high-avidity, autoimmune cross-reactions as a pathogenic sequela associated with anti-SARS-CoV-2 vaccines.

scholarly journals Human bocavirus 1 respiratory tract reactivations or reinfections in two adults, contributing to neurological deficits and death

2021 ◽  
Vol 3 (7) ◽  
Author(s):  
Rajita Rayamajhi Thapa ◽  
Annelie Plentz ◽  
Matthias Edinger ◽  
Daniel Wolff ◽  
Klemens Angstwurm ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Cross Reactivity ◽  
Neurological Deficits ◽  
Immunosuppressed Patient ◽  
Human Bocavirus ◽  
High Avidity ◽  
The Family ◽  
Colon Biopsy ◽  
Life Threatening ◽  
Tract Infections

Human bocavirus 1 (HBoV1) of the family Parvoviridae causes mild to life-threatening respiratory tract infections in young children, but, due to widespread immunity, it is uncommon in adults. HBoV1 reinfections or reactivations leading to casualties are rare, but might be underdiagnosed. We report two young adults, one previously healthy and one immunosuppressed, with rare diagnostic patterns of HBoV1 respiratory tract infection. Both patients exhibited very high loads of HBoV1 DNA in respiratory samples. The immunosuppressed patient was also HBoV1 DNA-positive in blood, stool and a colon biopsy, but exhibited prior HBoV1-specific high-avidity IgG and weak IgM positivity 9 months before the respiratory symptoms. Likewise, the previously healthy patient exhibited HBoV1 IgG of high avidity and very weak IgM in serum, pointing to prior immunity, but with a seroconversion in cerebrospinal fluid. This patient also showed strong HBoV2 cross-reactivity. The molecular and serological results, together with their ages, suggest that both patients exhibited unusual reinfection or reactivation of HBoV1, contributing to neurological deficits and death.

scholarly journals Development of an Enzyme-Linked Immunosorbent Assay To Detect Antibodies Targeting Recombinant Envelope Protein 2 of Mayaro Virus

2019 ◽  
Vol 57 (5) ◽  
Author(s):  
Marcílio Jorge Fumagalli ◽  
William Marciel de Souza ◽  
Marília Farignoli Romeiro ◽  
Michell Charles de Souza Costa ◽  
Renata Dezengrini Slhessarenko ◽  
...  
Keyword(s):  
Immunosorbent Assay ◽  
Envelope Protein ◽  
Cross Reactivity ◽  
Antibody Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Avidity ◽  
Serum Samples ◽  
Igg Antibody ◽  
Mayaro Virus ◽  
Recombinant Envelope Protein

ABSTRACT Mayaro virus (MAYV) is a neglected arthropod-borne virus (arbovirus) antigenically clustered into the Semliki Forest complex group of Alphavirus genus (Togaviridae family), maintained in an unclear zoonotic cycle involving mosquitoes from Haemagogus genus as the main vector. The genome is composed of a positive single-stranded RNA of 11.5 kb in length, which contains two genes that encode four nonstructural (nsP1 to nsP4) and five structural (C, E3, E2, 6K, and E1) proteins. In the present study, we have developed an enzyme-linked immunosorbent assay (ELISA) using as antigen the recombinant envelope protein 2 of MAYV produced in an Escherichia coli system (rE2-MAYV ELISAs). A panel of 68 human serum samples from suspected arboviral cases was analyzed and titrated for anti-MAYV IgM and IgG antibody detection. The rE2-MAYV ELISA detected 33.8% (23/68) IgG-positive samples, demonstrating 100% sensitivity and 78.95% specificity compared to the MAYV-specific 50% plaque reduction neutralization assay. In addition, the positive MAYV-neutralizing samples showed high titers of detection by rE2-MAYV ELISA, suggesting a highly sensitive test. The rE2-MAYV ELISA also detected 42.5% (29/68) IgM-positive samples, of which 13.8% (4/29) presented high-avidity interactions with rE2-MAYV. Cross-reactivity was observed with Chikungunya virus (CHIKV)-specific murine antibody sample but not with CHIKV-specific human and other Alphavirus murine antibodies. In short, we have developed a rapid, simple, specific, and sensitive MAYV rE2-ELISA, and our preliminary results show its potential applicability to diagnosis of MAYV infections.

scholarly journals Design and evaluation of engineered protein biosensors for live-cell imaging of EGFR phosphorylation

2019 ◽  
Vol 12 (584) ◽  
pp. eaap7584 ◽  
Author(s):  
Karthik Tiruthani ◽  
Adam Mischler ◽  
Shoeb Ahmed ◽  
Jessica Mahinthakumar ◽  
Jason M. Haugh ◽  
...  
Keyword(s):  
Protein Engineering ◽  
Combinatorial Library ◽  
Cross Reactivity ◽  
Sh2 Domain ◽  
Live Cell ◽  
Superior Performance ◽  
Mutant Form ◽  
High Avidity ◽  
Sh2 Domains ◽  
Kinetics Of

Live-cell fluorescence microscopy is broadly applied to study the dynamics of receptor-mediated cell signaling, but the availability of intracellular biosensors is limited. A biosensor based on the tandem SH2 domains from phospholipase C–γ1 (PLCγ1), tSH2-WT, has been used to measure phosphorylation of the epidermal growth factor receptor (EGFR). Here, we found that tSH2-WT lacked specificity for phosphorylated EGFR, consistent with the known promiscuity of SH2 domains. Further, EGF-stimulated membrane recruitment of tSH2-WT differed qualitatively from the expected kinetics of EGFR phosphorylation. Analysis of a mathematical model suggested, and experiments confirmed, that the high avidity of tSH2-WT resulted in saturation of its target and interference with EGFR endocytosis. To overcome the apparent target specificity and saturation issues, we implemented two protein engineering strategies. In the first approach, we screened a combinatorial library generated by random mutagenesis of the C-terminal SH2 domain (cSH2) of PLCγ1 and isolated a mutant form (mSH2) with enhanced specificity for phosphorylated Tyr992 (pTyr992) of EGFR. A biosensor based on mSH2 closely reported the kinetics of EGFR phosphorylation but retained cross-reactivity similar to tSH2-WT. In the second approach, we isolated a pTyr992-binding protein (SPY992) from a combinatorial library generated by mutagenesis of the Sso7d protein scaffold. Compared to tSH2-WT and mSH2, SPY992 exhibited superior performance as a specific, moderate-affinity biosensor. We extended this approach to isolate a biosensor for EGFR pTyr1148 (SPY1148). This approach of integrating theoretical considerations with protein engineering strategies can be generalized to design and evaluate suitable biosensors for various phospho-specific targets.

Human Prothrombin Activation: Determination of Plasma and Serum Levels of Prothrombin Fragment 3 by Radioimmunoassay

1979 ◽  
Author(s):  
Daniel Walz ◽  
Thomas Brown
Keyword(s):  
Blood Clotting ◽  
Factor Xa ◽  
Heart Association ◽  
Serum Levels ◽  
Cross Reactivity ◽  
Assay Procedure ◽  
A Chain ◽  
Prothrombin Activation ◽  
Theoretical Amount

Human prothrombin activation is unique in that, in addition to the release of fragment 1.2 (FI.2) from the NH-terminus of prothrombin by factor Xa during the generation of thrombin, an additional 13 residue polypeptide, fragment 3 (F3), is autocatalytically removed from the amino-terminus of the thrombin A chain. We have developed a rapid radioimmunoassay for human F3 which incorporates short incubation times and the use of a preprecipitated second antibody; the assay can be performed in three hours. Specificity studies in buffer systems show prothrombin and prethrombin 1 cross-reacting at a level of 0.001; purified thrombin does not cross-react. In the presence of 5% BSA, prothrombin displays considerably less cross-reactivity. No immunoreactive material to F3 antibodies could be detected in 400 μL of plasma. Serum, obtained from whole blood clotting, contained measurable quantities of F3 (40-100 ng/mL). This amount in serum represents only 5-10% of the theoretical amount available should all of the fragment be hydrolytically cleaved during the conversion of prothrombin to thrombin. This assay procedure is currently being utilized to monitor the activation of purified human prothrombin in the absence and presence of selected plasma inhibitors. (Supported in part by NIH 05384-17 and the Michigan Heart Association).

Cross-reactivity of organs in allograft rejection. Comparison of effect of thyroid allografts on established islet allografts

Diabetes ◽  
1987 ◽  
Vol 36 (11) ◽  
pp. 1268-1270
Author(s):  
K. Kover ◽  
O. Hegre ◽  
H. Popiela ◽  
T. Biggs ◽  
W. V. Moore
Keyword(s):  
Allograft Rejection ◽  
Cross Reactivity ◽  
Islet Allografts
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