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SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement.
Wang, Ying-Ting; Allen, Robert D; Kim, Kenneth; Shafee, Norazizah; Gonzalez, Andrew J; Nguyen, Michael N; Valentine, Kristen M; Cao, Xia; Lu, Lucy; Pai, Chin-I; Johnson, Sachi; Kerwin, Lisa; Zhou, Heyue; Zhang, Yanliang; Shresta, Sujan.
  • Wang YT; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
  • Allen RD; Sorrento Therapeutics, Inc., San Diego, CA, 92121, USA.
  • Kim K; Histopathology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
  • Shafee N; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
  • Gonzalez AJ; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
  • Nguyen MN; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
  • Valentine KM; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
  • Cao X; Sorrento Therapeutics, Inc., San Diego, CA, 92121, USA.
  • Lu L; Sorrento Therapeutics, Inc., San Diego, CA, 92121, USA.
  • Pai CI; Sorrento Therapeutics, Inc., San Diego, CA, 92121, USA.
  • Johnson S; Sorrento Therapeutics, Inc., San Diego, CA, 92121, USA.
  • Kerwin L; Sorrento Therapeutics, Inc., San Diego, CA, 92121, USA.
  • Zhou H; Sorrento Therapeutics, Inc., San Diego, CA, 92121, USA.
  • Zhang Y; Sorrento Therapeutics, Inc., San Diego, CA, 92121, USA.
  • Shresta S; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA. Electronic address: sujan@lji.org.
Antiviral Res ; 195: 105185, 2021 11.
Article in English | MEDLINE | ID: covidwho-1458855
ABSTRACT
Monoclonal antibodies (mAbs) are emerging as safe and effective therapeutics against SARS-CoV-2. However, variant strains of SARS-CoV-2 have evolved, with early studies showing that some mAbs may not sustain their efficacy in the face of escape mutants. Also, from the onset of the COVID-19 pandemic, concern has been raised about the potential for Fcγ receptor-mediated antibody-dependent enhancement (ADE) of infection. In this study, plaque reduction neutralization assays demonstrated that mAb 1741-LALA neutralizes SARS-CoV-2 strains B.1.351, D614 and D614G. MAbs S1D2-hIgG1 and S1D2-LALA mutant (STI-1499-LALA) did not neutralize B.1.351, but did neutralize SARS-CoV-2 strains D614 and D614G. LALA mutations did not result in substantial differences in neutralizing abilities between clones S1D2-hIgG1 vs STI-1499-LALA. S1D2-hIgG1, STI-1499-LALA, and convalescent plasma showed minimal ability to induce ADE in human blood monocyte-derived macrophages. Further, no differences in pharmacokinetic clearance of S1D2-hIgG1 vs STI-1499-LALA were observed in mice expressing human FcRn. These findings confirm that SARS-CoV-2 has already escaped some mAbs, and identify a mAb candidate that may neutralize multiple SARS-CoV-2 variants. They also suggest that risk of ADE in macrophages may be low with SARS-CoV-2 D614, and LALA Fc change impacts neither viral neutralization nor Ab clearance.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibody-Dependent Enhancement / SARS-CoV-2 / Antibodies, Monoclonal Type of study: Prognostic study Topics: Variants Limits: Animals / Humans Language: English Journal: Antiviral Res Year: 2021 Document Type: Article Affiliation country: J.antiviral.2021.105185

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibody-Dependent Enhancement / SARS-CoV-2 / Antibodies, Monoclonal Type of study: Prognostic study Topics: Variants Limits: Animals / Humans Language: English Journal: Antiviral Res Year: 2021 Document Type: Article Affiliation country: J.antiviral.2021.105185