scholarly journals Cross reactivity of neutralizing antibodies to the encephalitic California Serogroup orthobunyaviruses varies by virus and genetic relatedness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alyssa B. Evans ◽  
Karin E. Peterson
Keyword(s):  
Gold Standard ◽  
Neutralizing Antibodies ◽  
Viral Encephalitis ◽  
Genetic Relatedness ◽  
Cross Reactivity ◽  
Etiologic Agent ◽  
Snowshoe Hare ◽  
Neuroinvasive Disease ◽  
California Serogroup ◽  
High Degree

AbstractThe California Serogroup (CSG) of Orthobunyaviruses comprises several viruses capable of causing neuroinvasive disease in humans, including La Crosse (LACV), Snowshoe Hare (SSHV), Tahyna (TAHV), Jamestown Canyon (JCV), and Inkoo (INKV) viruses. Diagnosis of specific CSG viruses is complicated by the high degree of antibody cross-reactivity between them, with laboratory standards requiring a fourfold higher titer of neutralizating antibody (NAb) activity to positively identify the etiologic virus. To help elucidate NAb relationships between neuroinvasive CSG viruses, we directly compared the cross-reactivity of NAb between LACV, SSHV, TAHV, JCV, and INKV. Mice were inoculated with individual viruses and the NAb activity of plasma samples was compared by plaque reduction neutralization tests against all five viruses. Overall, the results from these studies show that the CSG viruses induced high levels of NAb against the inoculum virus, and differing amounts of cross-reactive NAb against heterologous viruses. LACV, SSHV, and INKV elicited the highest amount of cross-reactive NAb. Interestingly, a fourfold difference in NAb titer between the inoculum virus and the other CSG viruses was not always observed. Thus, NAb titers, which are the gold-standard for diagnosing the etiologic agent for viral encephalitis, may not clearly differentiate between different CSG viruses.

scholarly journals Roles of Host Species, Geographic Separation, and Isolation in the Seroprevalence of Jamestown Canyon and Snowshoe Hare Viruses in Newfoundland

2012 ◽  
Vol 78 (18) ◽  
pp. 6734-6740 ◽  
Author(s):  
Gregory Goff ◽  
Hugh Whitney ◽  
Michael A. Drebot
Keyword(s):  
Host Species ◽  
Neutralization Assay ◽  
Snowshoe Hare ◽  
Large Mammals ◽  
Content Type ◽  
Neuroinvasive Disease ◽  
Snowshoe Hares ◽  
Jamestown Canyon Virus ◽  
Geographic Separation ◽  
California Serogroup

ABSTRACTCalifornia serogroup viruses, including Jamestown Canyon virus (JCV) and snowshoe hare virus (SSHV), are mosquito-borne members of theBunyaviridaefamily and are endemic across North America. These arboviruses are potential pathogens which occasionally cause neuroinvasive disease in humans and livestock. A neutralization assay was used to document JCV and SSHV seroprevalence using blood collected from a variety of domestic and wildlife host species. These species were sampled in an island setting, Newfoundland, which contains diverse ecoregions, ecological landscapes, and habitats. Seroprevalence rates for each virus differed significantly among host species and within certain species across different geographic areas. JCV was significantly associated with large mammals, and SSHV was significantly associated with snowshoe hares. Seroprevalence rates in the 5 species of animals tested for prior exposure to JCV ranged from 0% in snowshoe hares to 64% in horses. Seroprevalence rates for SSHV ranged from less than 1% in bovines to 55% in all snowshoe hares. The seroprevalence of SSHV differed significantly (P< 0.05) among hares occupying the discrete habitats of watersheds separated by 14 to 35 km. Cattle on farms in boreal forest landscapes displayed significantly higher JCV seroprevalence (P< 0.001) than those on farms located in seacoast landscapes. Lifelong geographic isolation of cattle to insular Newfoundland was associated with significantly lower JCV seroprevalence (P< 0.01) than that for cattle which had lived off-island.

scholarly journals Aptamer BC 007’s Affinity to Specific and Less-Specific Anti-SARS-CoV-2 Neutralizing Antibodies

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 932
Author(s):  
Annekathrin Haberland ◽  
Oxana Krylova ◽  
Heike Nikolenko ◽  
Peter Göttel ◽  
Andre Dallmann ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Cross Reactivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Resonance Spectroscopy ◽  
Plastic Plate ◽  
Calorimetric Titration ◽  
Background Signal ◽  
High Background ◽  
Specific Virus ◽  
Binding Sequence

COVID-19 is a pandemic respiratory disease that is caused by the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anti-SARS-CoV-2 antibodies are essential weapons that a patient with COVID-19 has to combat the disease. When now repurposing a drug, namely an aptamer that interacts with SARS-CoV-2 proteins for COVID-19 treatment (BC 007), which is, however, a neutralizer of pathogenic autoantibodies in its original indication, the possibility of also binding and neutralizing anti-SARS-CoV-2 antibodies must be considered. Here, the highly specific virus-neutralizing antibodies have to be distinguished from the ones that also show cross-reactivity to tissues. The last-mentioned could be the origin of the widely reported SARS-CoV-2-induced autoimmunity, which should also become a target of therapy. We, therefore, used enzyme-linked immunosorbent assay (ELISA) technology to assess the binding of well-characterized publicly accessible anti-SARS-CoV-2 antibodies (CV07-209 and CV07-270) with BC 007. Nuclear magnetic resonance spectroscopy, isothermal calorimetric titration, and circular dichroism spectroscopy were additionally used to test the binding of BC 007 to DNA-binding sequence segments of these antibodies. BC 007 did not bind to the highly specific neutralizing anti-SARS-CoV-2 antibody but did bind to the less specific one. This, however, was a lot less compared to an autoantibody of its original indication (14.2%, range 11.0–21.5%). It was also interesting to see that the less-specific anti-SARS-CoV-2 antibody also showed a high background signal in the ELISA (binding on NeutrAvidin-coated or activated but noncoated plastic plate). These initial experiments suggest that the risk of binding and neutralizing highly specific anti-SARS CoV-2 antibodies by BC 007 should be low.

Immune Evasion of SARS-CoV-2 Variants of Concern is Driven by Low Affinity to Neutralizing Antibodies

2021 ◽  
Author(s):  
Matheus Ferraz ◽  
Emerson Moreira ◽  
Danilo F. Coêlho ◽  
Gabriel Wallau ◽  
Roberto Lins
Keyword(s):  
Immune Evasion ◽  
Neutralizing Antibodies ◽  
Cross Reactivity ◽  
Class I ◽  
Minor Role ◽  
A Minor

SARS-CoV-2 VOCs immune evasion is mainly due to lower cross-reactivity from previously elicited class I/II neutralizaing antibodies, while increased affinity to hACE2 plays a minor role. Affinity between antibodies and...

scholarly journals Chronic Constrictive Pericarditis

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Hossein Doustkami ◽  
Afshin Hooshyar ◽  
Nasrollah Maleki ◽  
Zahra Tavosi ◽  
Iraj Feizi
Keyword(s):  
Cardiac Catheterization ◽  
Constrictive Pericarditis ◽  
Gold Standard ◽  
Elevated Serum ◽  
Disease Process ◽  
Clinical Suspicion ◽  
Rare Clinical Entity ◽  
Good Recovery ◽  
Prompt Treatment ◽  
High Degree

Constrictive pericarditis (CP) is a rare clinical entity that can pose diagnostic problems. The diagnosis of CP requires a high degree of clinical suspicion. The gold standard for diagnosis is cardiac catheterization with analysis of intracavitary pressure curves, which are high and, in end diastole, equal in all chambers. We present a patient with unexplained dyspnea, recurrent right-side pleural effusion, and ascites. Analysis of the ascitic fluid revealed a high protein content and an elevated serum-ascites gradient. Echocardiography, computed tomography, and cardiac catheterization revealed the diagnosis of CP. He underwent complete pericardiectomy and to date has made a good recovery. The diagnosis of CP is often neglected by admitting physicians, who usually attribute the symptoms to another disease process. This case exemplifies the difficulty in diagnosing this condition, as well as the investigation required, and provides a discussion of the benefit and outcomes of prompt treatment.

scholarly journals Human immunodeficiency virus 1. Predominance of a group-specific neutralizing epitope that persists despite genetic variation.

1989 ◽  
Vol 170 (5) ◽  
pp. 1681-1695 ◽  
Author(s):  
I Berkower ◽  
G E Smith ◽  
C Giri ◽  
D Murphy
Keyword(s):  
Genetic Diversity ◽  
Human Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Neutralizing Epitope ◽  
Vaccine Strategy ◽  
Disease Pathogenesis ◽  
Immunodeficiency Virus ◽  
High Degree ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

HIV-1 is known to show a high degree of genetic diversity, which may have major implications for disease pathogenesis and prevention. If every divergent isolate represented a distinct serotype, then effective vaccination might be impossible. However, using a sensitive new plaque-forming assay for HIV-1, we have found that most infected patients make neutralizing antibodies, predominantly to a group-specific epitope shared among three highly divergent isolates. This epitope persists among divergent isolates and rarely mutates, despite the rapid overall mutation rate of HIV-1, suggesting that it may participate in an essential viral function. These findings, plus the rarity of reinfections among these patients, suggest that HIV-1 may be more susceptible to a vaccine strategy based on a group-specific neutralizing epitope than was previously suspected.

scholarly journals Broad cross-reactivity across sarbecoviruses exhibited by a subset of COVID-19 donor-derived neutralizing antibodies

2021 ◽  
Author(s):  
Claudia A. Jette ◽  
Alexander A. Cohen ◽  
Priyanthi N.P. Gnanapragasam ◽  
Frauke Muecksch ◽  
Yu E. Lee ◽  
...  
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Cross Reactivity ◽  
Antibody Therapeutics ◽  
Binding Domains ◽  
Cryptic Epitope ◽  
Binding Antibody ◽  
Β Sheet ◽  
Potent Neutralization

SummaryMany anti-SARS-CoV-2 neutralizing antibodies target the ACE2-binding site on viral spike receptor-binding domains (RBDs). The most potent antibodies recognize exposed variable epitopes, often rendering them ineffective against other sarbecoviruses and SARS-CoV-2 variants. Class 4 anti-RBD antibodies against a less-exposed, but more-conserved, cryptic epitope could recognize newly-emergent zoonotic sarbecoviruses and variants, but usually show only weak neutralization potencies. We characterized two class 4 anti-RBD antibodies derived from COVID-19 donors that exhibited broad recognition and potent neutralization of zoonotic coronavirus and SARS-CoV-2 variants. C118-RBD and C022-RBD structures revealed CDRH3 mainchain H-bond interactions that extended an RBD β-sheet, thus reducing sensitivity to RBD sidechain changes, and epitopes that extended from the cryptic epitope to occlude ACE2 binding. A C118-spike trimer structure revealed rotated RBDs to allow cryptic epitope access and the potential for intra-spike crosslinking to increase avidity. These studies facilitate vaccine design and illustrate potential advantages of class 4 RBD-binding antibody therapeutics.

scholarly journals Progress in the rational design of an AIDS vaccine

2011 ◽  
Vol 366 (1579) ◽  
pp. 2759-2765 ◽  
Author(s):  
Gary J. Nabel ◽  
Peter D. Kwong ◽  
John R. Mascola
Keyword(s):  
Structural Biology ◽  
Neutralizing Antibodies ◽  
Rational Design ◽  
Computational Modelling ◽  
Effective Vaccine ◽  
Aids Vaccine ◽  
Immunodeficiency Virus ◽  
High Degree ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Human immunodeficiency virus-1 (HIV-1) has a high degree of genetic and antigenic diversity that has impeded the development of an effective vaccine using traditional methods. We are attempting to develop an AIDS vaccine by employing strategies that include structural biology and computational modelling, in an effort to develop immunogens capable of eliciting neutralizing antibodies of the requisite breadth and potency against circulating strains of HIV-1.

scholarly journals Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets

2008 ◽  
Vol 83 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Zhongying Chen ◽  
Celia Santos ◽  
Amy Aspelund ◽  
Laura Gillim-Ross ◽  
Hong Jin ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Serum Antibody ◽  
Cross Reactivity ◽  
Phenotypic Properties ◽  
Vaccine Candidates ◽  
Virus Challenge ◽  
Avian Influenza A Virus ◽  
Internal Gene

ABSTRACT Avian influenza A virus A/teal/HK/W312/97 (H6N1) possesses seven gene segments that are highly homologous to those of highly pathogenic human influenza H5N1 viruses, suggesting that a W312-like H6N1 virus might have been involved in the generation of the A/HK/97 H5N1 viruses. The continuous circulation and reassortment of influenza H6 subtype viruses in birds highlight the need to develop an H6 vaccine to prevent potential influenza pandemics caused by the H6 viruses. Based on the serum antibody cross-reactivity data obtained from 14 different H6 viruses from Eurasian and North American lineages, A/duck/HK/182/77, A/teal/HK/W312/97, and A/mallard/Alberta/89/85 were selected to produce live attenuated H6 candidate vaccines. Each of the H6 vaccine strains is a 6:2 reassortant ca virus containing HA and NA gene segments from an H6 virus and the six internal gene segments from cold-adapted A/Ann Arbor/6/60 (AA ca), the master donor virus that is used to make live attenuated influenza virus FluMist (intranasal) vaccine. All three H6 vaccine candidates exhibited phenotypic properties of temperature sensitivity (ts), ca, and attenuation (att) conferred by the internal gene segments from AA ca. Intranasal administration of a single dose of the three H6 ca vaccine viruses induced neutralizing antibodies in mice and ferrets and fully protected mice and ferrets from homologous wild-type (wt) virus challenge. Among the three H6 vaccine candidates, the A/teal/HK/W312/97 ca virus provided the broadest cross-protection against challenge with three antigenically distinct H6 wt viruses. These data support the rationale for further evaluating the A/teal/HK/W312/97 ca vaccine in humans.

Abstract 496: Genetic Neutrophil Deficiency Ameliorates Cerebral Ischemia-Reperfusion Injury

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Ryan A Frieler ◽  
Yutein Chung ◽  
Jianrui Song ◽  
Thomas M Vigil ◽  
Richard M Mortensen
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Knockout Mice ◽  
Neutralizing Antibodies ◽  
Immune Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Types ◽  
Artery Occlusion ◽  
Cross Reactivity

Background: Neutrophils respond rapidly to cerebral ischemia and are thought to contribute to inflammation-mediated injury during stroke. Neutralizing antibodies and inhibition of neutrophil chemotactic molecules can be protective during models of stroke, but many of these techniques have the potential to result in cross-reactivity and non-specificity with other immune cell types. Using myeloid Mcl1 knockout mice as a model of genetic neutrophil deficiency, we investigated the contribution of neutrophils to stroke pathophysiology. Methods: Myeloid Mcl1 knockout mice were subjected to transient 90-min middle cerebral artery occlusion and infarct size was assessed by MRI after 24 hours reperfusion. Immune cell mobilization and infiltration was assessed by flow cytometry after 24 hours reperfusion. Results: We found that myeloid Mcl1 knockout mice had significantly reduced infarct size when compared to heterozygous and wild type control mice (MyMcl1 +/+ : 78.0 mm 3 ; MyMcl1 +/- : 83.4 mm 3 ; MyMcl1 -/- : 55.1 mm 3 ). This was accompanied by a nearly complete absence of neutrophils in the ischemic hemisphere of myeloid Mcl1 knockout mice. Although myeloid Mcl1 knockout mice were protected from cerebral infarction, no significant differences in the expression of inflammatory genes were detected. Inhibition of neutrophil chemotaxis using CXCR2 pepducin treatment partially reduced neutrophil mobilization and recruitment to the brain after stroke, but did not reduce infarct size 24 hours after transient MCA occlusion. Conclusions: These data confirm that neutrophils have an important role in infarct development during stroke pathophysiology and suggest that complete deficiency, but not partial inhibition, is necessary to prevent neutrophil-mediated injury during stroke.

scholarly journals Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients

2020 ◽  
Vol 5 (52) ◽  
pp. eabe0367 ◽  
Author(s):  
Anita S. Iyer ◽  
Forrest K. Jones ◽  
Ariana Nodoushani ◽  
Meagan Kelly ◽  
Margaret Becker ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Serum Antibody ◽  
Cross Reactivity ◽  
Binding Domain ◽  
Antibody Responses ◽  
Human Antibody ◽  
Receptor Binding Domain ◽  
Recent Infection

We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.

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