scholarly journals Structural Analysis of Mutants of High-Affinity and Low-Affinity p-Azophenylarsonate-Specific Antibodies Generated by Alanine Scanning of Heavy Chain Complementarity-Determining Region 2

2001 ◽  
Vol 167 (9) ◽  
pp. 5129-5135 ◽  
Author(s):  
Behnaz Parhami-Seren ◽  
Malini Viswanathan ◽  
Roland K. Strong ◽  
Michael N. Margolies
Keyword(s):  
Structural Analysis ◽  
Heavy Chain ◽  
Alanine Scanning ◽  
Specific Antibodies ◽  
High Affinity ◽  
Complementarity Determining Region

Characterization of a high-affinity human antibody with a disulfide bridge in the third complementarity-determining region of the heavy chain

2012 ◽  
Vol 25 (3) ◽  
pp. 125-135 ◽  
Author(s):  
Juan Carlos Almagro ◽  
Gopalan Raghunathan ◽  
Eric Beil ◽  
Dariusz J. Janecki ◽  
Qiang Chen ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Disulfide Bridge ◽  
Human Antibody ◽  
High Affinity ◽  
The Third ◽  
Complementarity Determining Region

scholarly journals A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice

2021 ◽  
Author(s):  
David R. Martinez ◽  
Alexandra Schaefer ◽  
Sophie Gobeil ◽  
Dapeng Li ◽  
Gabriela De la Cruz ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Receptor Binding ◽  
Specific Antibody ◽  
Neutralizing Antibody ◽  
Affinity Binding ◽  
Receptor Binding Domain ◽  
High Affinity Binding ◽  
High Affinity ◽  
Broadly Neutralizing Antibody ◽  
Conserved Epitope

AbstractSARS-CoV in 2003, SARS-CoV-2 in 2019, and SARS-CoV-2 variants of concern (VOC) can cause deadly infections, underlining the importance of developing broadly effective countermeasures against Group 2B Sarbecoviruses, which could be key in the rapid prevention and mitigation of future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV, bat CoVs WIV-1 and RsSHC014, and SARS-CoV-2 variants D614G, B.1.1.7, B.1.429, B1.351 by a receptor-binding domain (RBD)-specific antibody DH1047. Prophylactic and therapeutic treatment with DH1047 demonstrated protection against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B1.351infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among Sarbecoviruses. We conclude that DH1047 is a broadly neutralizing and protective antibody that can prevent infection and mitigate outbreaks caused by SARS-like strains and SARS-CoV-2 variants. Our results argue that the RBD conserved epitope bound by DH1047 is a rational target for pan Group 2B coronavirus vaccines.

scholarly journals Impact of Immunoglobulin Isotype and Epitope on the Functional Properties of Vibrio cholerae O-Specific Polysaccharide-Specific Monoclonal Antibodies

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Robert C. Kauffman ◽  
Oluwaseyi Adekunle ◽  
Hanyi Yu ◽  
Alice Cho ◽  
Lindsay E. Nyhoff ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Functional Properties ◽  
Diarrheal Disease ◽  
Cross Linking ◽  
Specific Antibodies ◽  
Immunoglobulin Isotype ◽  
High Affinity ◽  
O Antigen ◽  
The Impact ◽  
Motility Inhibition

ABSTRACT Vibrio cholerae causes the severe diarrheal disease cholera. Clinical disease and current oral cholera vaccines generate antibody responses associated with protection. Immunity is thought to be largely mediated by lipopolysaccharide (LPS)-specific antibodies, primarily targeting the O-antigen. However, the properties and protective mechanism of functionally relevant antibodies have not been well defined. We previously reported on the early B cell response to cholera in a cohort of Bangladeshi patients, from which we characterized a panel of human monoclonal antibodies (MAbs) isolated from acutely induced plasmablasts. All antibodies in that previous study were expressed in an IgG1 backbone irrespective of their original isotype. To clearly determine the impact of affinity, immunoglobulin isotype and subclass on the functional properties of these MAbs, we re-engineered a subset of low- and high-affinity antibodies in different isotype and subclass immunoglobulin backbones and characterized the impact of these changes on binding, vibriocidal, agglutination, and motility inhibition activity. While the high-affinity antibodies bound similarly to O-antigen, irrespective of isotype, the low-affinity antibodies displayed significant avidity differences. Interestingly, despite exhibiting lower binding properties, variants derived from the low-affinity MAbs had comparable agglutination and motility inhibition properties to the potently binding antibodies, suggesting that how the MAb binds to the O-antigen may be critical to function. In addition, not only pentameric IgM and dimeric IgA, but also monomeric IgA, was remarkably more potent than their IgG counterparts at inhibiting motility. Finally, analyzing highly purified F(ab) versions of these antibodies, we show that LPS cross-linking is essential for motility inhibition. IMPORTANCE Immunity to the severe diarrheal disease cholera is largely mediated by lipopolysaccharide (LPS)-specific antibodies. However, the properties and protective mechanisms of functionally relevant antibodies have not been well defined. Here, we have engineered low and high-affinity LPS-specific antibodies in different immunoglobulin backbones in order to assess the impact of affinity, immunoglobulin isotype, and subclass on binding, vibriocidal, agglutination, and motility inhibition functional properties. Importantly, we found that affinity did not directly dictate functional potency since variants derived from the low-affinity MAbs had comparable agglutination and motility inhibition properties to the potently binding antibodies. This suggests that how the antibody binds sterically may be critical to function. In addition, not only pentameric IgM and dimeric IgA, but also monomeric IgA, was remarkably more potent than their IgG counterparts at inhibiting motility. Finally, analyzing highly purified F(ab) versions of these antibodies, we show that LPS cross-linking is essential for motility inhibition.

scholarly journals Favored use of immunoglobulin V(H)4 Genes in AIDS-associated B-cell lymphoma

Blood ◽  
1996 ◽  
Vol 88 (1) ◽  
pp. 252-260 ◽  
Author(s):  
A Bessudo ◽  
V Cherepakhin ◽  
TA Johnson ◽  
LZ Rassenti ◽  
E Feigal ◽  
...  
Keyword(s):  
B Cell ◽  
Heavy Chain ◽  
Variable Region ◽  
B Cell Lymphoma ◽  
Acquired Immunodeficiency ◽  
Somatic Diversification ◽  
Immunodeficiency Syndrome ◽  
Variable Region Genes ◽  
Ig Heavy Chain ◽  
Complementarity Determining Region

Abstract We examined the lg heavy chain variable region genes (Ig V(H) genes) expressed in biopsy specimens of 10 patients with acquired immunodeficiency syndrome (AIDS)-associated lymphoma. Eight expressed Ig V(H) genes of the V(H)4 group, indicating a bias toward expression of Ig V(H) genes of this subgroup. Sequence analyses of Ig V(H) genes isolated from any one lymphoma did not reveal evidence for intraclonal diversity. However, some lymphomas express Ig V(H) genes that apparently have undergone somatic diversification and selection. In addition, we found that the sequence encoding each examined third complementarity determining region most likely resulted from D-D fusion, a process that ordinarily contributes to the generation of a relatively small proportion of the Ig heavy chain genes expressed by normal adult B cells. The noted restriction in the use of Ig V(H) genes by AIDS-associated B-cell lymphomas suggests that antigenic stimulation contributes to lymphomagenesis in patients with AIDS.

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