Recombinant mouse monoclonal antibodies with single amino acid substitutions affecting C1q and high affinity Fc receptor binding have identical serum half-lives in the BALB/c mouse

AbstractEmerging mutations in SARS-CoV-2 cause several waves of COVID-19 pandemic. Here we investigate the infectivity and antigenicity of ten emerging SARS-CoV-2 variants—B.1.1.298, B.1.1.7(Alpha), B.1.351(Beta), P.1(Gamma), P.2(Zeta), B.1.429(Epsilon), B.1.525(Eta), B.1.526-1(Iota), B.1.526-2(Iota), B.1.1.318—and seven corresponding single amino acid mutations in the receptor-binding domain using SARS-CoV-2 pseudovirus. The results indicate that the pseudovirus of most of the SARS-CoV-2 variants (except B.1.1.298) display slightly increased infectivity in human and monkey cell lines, especially B.1.351, B.1.525 and B.1.526 in Calu-3 cells. The K417N/T, N501Y, or E484K-carrying variants exhibit significantly increased abilities to infect mouse ACE2-overexpressing cells. The activities of furin, TMPRSS2, and cathepsin L are increased against most of the variants. RBD amino acid mutations comprising K417T/N, L452R, Y453F, S477N, E484K, and N501Y cause significant immune escape from 11 of 13 monoclonal antibodies. However, the resistance to neutralization by convalescent serum or vaccines elicited serum is mainly caused by the E484K mutation. The convalescent serum from B.1.1.7- and B.1.351-infected patients neutralized the variants themselves better than other SARS-CoV-2 variants. Our study provides insights regarding therapeutic antibodies and vaccines, and highlights the importance of E484K mutation.

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Site-specific mutagenesis of human apolipoprotein E. Receptor binding activity of variants with single amino acid substitutions.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)68957-4 ◽

1988 ◽

Vol 263 (8) ◽

pp. 3542-3545 ◽

Cited By ~ 13

Author(s):

A Lalazar ◽

K H Weisgraber ◽

S C Rall ◽

H Giladi ◽

T L Innerarity ◽

...

Keyword(s):

Amino Acid ◽

Apolipoprotein E ◽

Receptor Binding ◽

Binding Activity ◽

Single Amino Acid ◽

Amino Acid Substitutions ◽

Site Specific ◽

Human Apolipoprotein ◽

Receptor Binding Activity

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Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016

10.1101/2021.02.17.431683 ◽

2021 ◽

Cited By ~ 10

Author(s):

Tyler N. Starr ◽

Allison J. Greaney ◽

Adam S. Dingens ◽

Jesse D. Bloom

Keyword(s):

Monoclonal Antibody ◽

Monoclonal Antibodies ◽

Amino Acid ◽

Receptor Binding ◽

Binding Domain ◽

Single Amino Acid ◽

Receptor Binding Domain ◽

Antigenic Evolution

AbstractMonoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for COVID-19. However, ongoing evolution of SARS-CoV-2 can render monoclonal antibodies ineffective. Here we completely map all mutations to the SARS-CoV-2 spike receptor binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escape LY-CoV016). Additionally, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts should diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to antigenic evolution of SARS-CoV-2.

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Monoclonal antibodies to CD44 and their influence on hyaluronan recognition.

The Journal of Cell Biology ◽

10.1083/jcb.130.2.485 ◽

1995 ◽

Vol 130 (2) ◽

pp. 485-495 ◽

Cited By ~ 90

Author(s):

Z Zheng ◽

S Katoh ◽

Q He ◽

K Oritani ◽

K Miyake ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Amino Acid ◽

Tumor Metastasis ◽

Single Amino Acid ◽

Cross Linking ◽

Amino Acid Substitutions ◽

Antibody Specificity ◽

Lymphocyte Migration ◽

Antibody Recognition ◽

Blocking Antibodies

Antibodies to CD44 have been used to inhibit a variety of processes which include lymphohemopoiesis, lymphocyte migration, and tumor metastasis. Some, but not all, CD44-mediated functions derive from its ability to serve as a receptor for hyaluronan (HA). However, sites on CD44 that interact with either ligands or antibodies are poorly understood. Interspecies rat/mouse CD44 chimeras were used to analyze the specificity of 25 mAbs and to determine that they recognize at least seven epitopes. Amino acid substitutions that resulted in loss of antibody recognition were all located in the region of homology to other cartilage link family proteins. While at least five epitopes were eliminated by single amino acid replacements, multiple residues had to be changed to destroy binding by other antibodies. One antibody was sensitive to changes in any of three separate parts of the molecule and some antibodies to distinct epitopes cross-blocked each other. Certain antibodies had the ability to increase HA binding by lymphocytes but this did not correlate absolutely with antibody specificity and was only partially attributable to CD44 cross-linking. Antibodies that consistently blocked HA recognition were all sensitive to amino acid changes within a short stretch of CD44. Such blocking antibodies interacted with CD44 more strongly than ligand in competition experiments. One large group of antibodies blocked ligand binding, but only with a particular cell line. This detailed analysis adds to our understanding of functional domains within CD44 and requirements for antibodies to influence recognition of one ligand.

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Antigenic drift in influenza A viruses. I. Selection and characterization of antigenic variants of A/PR/8/34 [HON1] influenza virus with monoclonal antibodies

Journal of Experimental Medicine ◽

10.1084/jem.148.2.383 ◽

1978 ◽

Vol 148 (2) ◽

pp. 383-392 ◽

Cited By ~ 103

Author(s):

W Gerhard ◽

RG Webster

Keyword(s):

Influenza Virus ◽

Monoclonal Antibodies ◽

Amino Acid ◽

Influenza A ◽

Antigenic Drift ◽

Single Amino Acid ◽

Amino Acid Substitutions ◽

Parent Virus ◽

Influenza A Viruses

Antigenic variants of A/PR/8/34 [HON1] influenza virus were selected after a single passage of the parent virus in embryonated chicken eggs in the presence of monoclonal antibodies to this virus. The monoclonal antibodies were produced by a hybridoma and were specific for an antigenic determinant on the HA molecule of the parent virus. Seven antigenic variants were analyzed with 95 monoclonal anti-HA antibodies prepared in vitro in the splenic fragment culture system. Three subgroups of antigenic variants were distinguished. The antigenic changes were primarily recognized by monoclonal antibodies to the strain- specific determinants of the parental hemagglutinin (HA) molecule. Monoclonal antibodies to HA determinants shared (in an identical or cross-reactive form) by parental virus and more than three heterologous viruses of the HON1 and H1N1 subtypes were unable to recognize the antigenic change on the variants. Similarly, heterogeneous antibody preparations could not differentiate between parental and variant viruses. The results are compatible with the idea that the HA of PR8 has available a large repertoire of antigenic modifications that may result from single amino acid substitutions, and that antigenic changes can occur in the strain- specific determinants on the HA molecule in the absence of concomitant changes in the cross-reactive HA determinants. The findings suggest that antigenic drift, in order to be epidemiologically significant, probably requires a series of amino acid substitutions in, or close to, the antigenic area on the HA molecule.

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