scholarly journals A recurring YYDRxG pattern in broadly neutralizing antibodies to a conserved site on SARS-CoV-2, variants of concern, and related viruses

2021 ◽  
Author(s):  
Hejun Liu ◽  
Chengzi I. Kaku ◽  
Ge Song ◽  
Meng Yuan ◽  
Raiees Andrabi ◽  
...  
Keyword(s):  
Immune System ◽  
Neutralizing Antibodies ◽  
Human Antibody ◽  
Broadly Neutralizing Antibodies ◽  
Human Immune System ◽  
Neutralization Activity ◽  
Humoral Immune ◽  
Humoral Immune System ◽  
Targeting Strategy ◽  
Conserved Epitope

Studying the antibody response to SARS-CoV-2 informs on how the human immune system can respond to antigenic variants as well as other SARS-related viruses. Here, we structurally and functionally characterized a potent human antibody ADI-62113 that also neutralizes SARS-CoV- 2 variants of concern and cross-reacts with many other sarbecoviruses. A YYDRxG motif encoded by IGHD3-22 in CDR H3 facilitates targeting to a highly conserved epitope on the SARS-CoV-2 receptor binding domain. A computational search for a YYDRxG pattern in publicly available sequences identified many antibodies with broad neutralization activity against SARS-CoV-2 variants and SARS-CoV. Thus, the YYDRxG motif represents a common convergent solution for the human humoral immune system to counteract sarbecoviruses. These findings also suggest an epitope targeting strategy to identify potent and broadly neutralizing antibodies that can aid in the design of pan-sarbecovirus vaccines and antibody therapeutics.

scholarly journals Novel neutralization mechanism of a human antibody with pan-coronavirus reactivity

2021 ◽  
Author(s):  
Xiaoyu Sun ◽  
Chunyan Yi ◽  
Yuanfei Zhu ◽  
Longfei Ding ◽  
Shuai Xia ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Broad Spectrum ◽  
Neutralizing Antibodies ◽  
Fusion Peptide ◽  
Spike Protein ◽  
Human Antibody ◽  
Broadly Neutralizing Antibodies ◽  
Neutralization Activity ◽  
Treatment Models ◽  
Trimeric Structure

Abstract The recurrent outbreak of coronaviruses and variants underscores the need for broadly reactive antivirals and vaccines. Here, a novel broad-spectrum human antibody named 76E1 was isolated from a COVID-19 convalescent patient and showed broad neutralization activity against multiple α- and β-coronaviruses, including the SARS-CoV-2 variants and also exhibited the binding breath to peptides containing the epitope from γ- and δ- coronaviruses. 76E1 cross-protects mice from SARS-CoV-2 and HCoV-OC43 infection in both prophylactic and treatment models. The epitope including the fusion peptide and S2’ cleavage site recognized by 76E1 was significantly conserved among α-, β-, γ- and δ- coronaviruses. We uncovered a novel mechanism of antibody neutralization that the epitope of 76E1 was proportionally less exposed in the prefusion trimeric structure of spike protein but could be unmasked by binding to the receptor ACE2. Once the epitope exposed, 76E1 inhibited S2’ cleavage, thus blocked the membrane fusion process. Our data demonstrate a key epitope targeted by broadly-neutralizing antibodies and will guide next-generation epitope-based pan-coronavirus vaccine design.

scholarly journals Unique structural solution from a VH3-30 antibody targeting the hemagglutinin stem of influenza A viruses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wayne D. Harshbarger ◽  
Derrick Deming ◽  
Gordon J. Lockbaum ◽  
Nattapol Attatippaholkun ◽  
Maliwan Kamkaew ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Influenza A ◽  
Critical Role ◽  
Binding Activity ◽  
Human Antibody ◽  
Broadly Neutralizing Antibodies ◽  
Influenza A Viruses ◽  
Universal Vaccine ◽  
Structural Details ◽  
Structural Solution

AbstractBroadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among VH3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of VH3-30 antibodies and reveals that 3I14 represents a novel structural solution within the VH3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV.

scholarly journals A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jean-François Bruxelle ◽  
Tess Kirilenko ◽  
Nino Trattnig ◽  
Yiqiu Yang ◽  
Matteo Cattin ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Envelope Protein ◽  
Protein Sequence ◽  
Neutralizing Antibodies ◽  
Human Antibody ◽  
Broadly Neutralizing Antibodies ◽  
Specific Antibodies ◽  
Strong Binding ◽  
Hiv Envelope ◽  
Hiv 1

AbstractThe occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM197-conjugate of a previously reported oligomannose mimetic. Oligomannose-specific bnAbs that are less dependent on interactions with the HIV envelope protein sequence showed strong binding to the glycoconjugates, with affinities approximating those reported for their cognate epitope. The glycoconjugate is also recognized by inferred germline precursors of oligomannose-specific bnAbs, albeit with the expected low avidity, supporting its potential as an immunogen. Immunization of human-antibody transgenic mice revealed that only a TLR4-stimulating adjuvant formulation resulted in antibodies able to bind a panel of recombinant HIV trimers. These antibodies bound at relatively modest levels, possibly explaining their inability to neutralize HIV infectivity. Nevertheless, these findings contribute further to understanding conditions for eliciting HIV-cross-reactive oligomannose-specific antibodies and inform on next steps for improving on the elicited response.

Serum immunoglobulins in patients with chronic tonsillitis

1984 ◽  
Vol 98 (12) ◽  
pp. 1213-1216 ◽  
Author(s):  
Harbans Lal ◽  
O. P. Sachdeva ◽  
H. R. Mehta
Keyword(s):  
Immune System ◽  
Mean Value ◽  
The Body ◽  
Antigenic Stimulation ◽  
Chronic Tonsillitis ◽  
Serum Immunoglobulin ◽  
Control Group ◽  
Humoral Immune ◽  
Humoral Immune System ◽  
The Mean

AbstractSerum immunoglobulin (IgG, IgA and IgM) levels were determined in patients with chronic tonsillitis before and one month after tonsillectomy. The preoperative levels of serum IgG, IgA and IgM were significantly higher when compared with the controls. The increase may be due to repeated antigenic stimulation. The post-operative levels for the three immunoglobulins were decreased; however, a significant reduction was observed for IgG only where the mean value was comparable with the control group. The data confirm that tonsillectomy does not disturb the humoral immune system of the body.

Stress response and humoral immune system alterations related to chronic hypergravity in mice

2012 ◽  
Vol 37 (1) ◽  
pp. 137-147 ◽  
Author(s):  
Nathan Guéguinou ◽  
Mickaël Bojados ◽  
Marc Jamon ◽  
Hanane Derradji ◽  
Sarah Baatout ◽  
...  
Keyword(s):  
Immune System ◽  
Stress Response ◽  
Humoral Immune ◽  
Humoral Immune System

scholarly journals Host-pathogen coevolution and the emergence of broadly neutralizing antibodies in chronic infections

2015 ◽  
Author(s):  
Armita Nourmohammad ◽  
Jakub Otwinowski ◽  
Joshua B Plotkin
Keyword(s):  
Immune System ◽  
Neutralizing Antibodies ◽  
Adaptive Immune System ◽  
Analytical Framework ◽  
Mathematical Framework ◽  
Broadly Neutralizing Antibodies ◽  
Chronic Infections ◽  
Adaptive Immune ◽  
Immune Parameters ◽  
Genotype Frequencies

The vertebrate adaptive immune system provides a flexible and diverse set of molecules to neutralize pathogens. Yet, viruses such as HIV can cause chronic infections by evolving as quickly as the adaptive immune system, forming an evolutionary arms race. Here we introduce a mathematical framework to study the coevolutionary dynamics of antibodies with antigens within a host. We focus on changes in the binding interactions between the antibody and antigen populations, which result from the underlying stochastic evolution of genotype frequencies driven by mutation, selection, and drift. We identify the critical viral and immune parameters that determine the distribution of antibody-antigen binding affinities. We also identify definitive signatures of coevolution that measure the reciprocal response between antibodies and viruses, and we introduce experimentally measurable quantities that quantify the extent of adaptation during continual coevolution of the two opposing populations. Using this analytical framework, we infer rates of viral and immune adaptation based on time-shifted neutralization assays in two HIV-infected patients. Finally, we analyze competition between clonal lineages of antibodies and characterize the fate of a given lineage in terms of the state of the antibody and viral populations. In particular, we derive the conditions that favor the emergence of broadly neutralizing antibodies, which may be useful in designing a vaccine against HIV.

scholarly journals Association between serum markers of the humoral immune system and inflammation in the Swedish AMORIS study

2020 ◽  
Author(s):  
aida santaolalla ◽  
Sam Sollie ◽  
Ali Rislan ◽  
Debra H. Josephs ◽  
Niklas Hammar ◽  
...  
Keyword(s):  
Immune System ◽  
Educational Level ◽  
Blood Cells ◽  
Adaptive Response ◽  
White Blood Cells ◽  
Principal Component ◽  
Serum Markers ◽  
Response Component ◽  
Humoral Immune ◽  
Humoral Immune System

Abstract Background: Although the onset of inflammatory cascades may profoundly influence the nature of antibody responses, the interplay between inflammatory and humoral (antibody) immune markers remains unclear. Thus, we explored the reciprocity between the humoral immune system and inflammation and assessed how external socio-demographic factors may influence these interactions.Methods: From the AMORIS cohort, 5,513 individuals were identified with baseline measurements of serum humoral immune (immunoglobulin G, A & M (IgG, IgA, IgM)) and inflammation (C-reactive protein (CRP), albumin, haptoglobin, white blood cells (WBC), iron and total iron-binding capacity) markers measured on the same day. Correlation analysis, principal component analysis and hierarchical clustering were used to evaluate biomarkers correlation, variation and associations. Multivariate analysis of variance was used to assess associations between biomarkers and educational level, socio-economic status, sex and age.Results: Frequently used serum markers for inflammation, CRP, haptoglobin and white blood cells, correlated together. Hierarchical clustering and principal component analysis confirmed the interaction between these main biological responses, showing an acute response component (CRP, Haptoglobin, WBC, IgM) and adaptive response component (Albumin, Iron, TIBC, IgA, IgG). A socioeconomic gradient associated with worse health outcomes was observed, specifically low educational level, older age and male sex were associated with serum levels that indicated infection and inflammation.Conclusions: These findings indicate that serum markers of the humoral immune system and inflammation closely interact in response to infection or inflammation. Clustering analysis presented two main immune response components: an acute and an adaptive response, comprising markers of both biological pathways. Future studies should shift from single internal marker assessment to multiple humoral and inflammation serum markers combined, when assessing risk of clinical outcomes such as cancer.

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