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Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines.
Bartsch, Yannic C; Tong, Xin; Kang, Jaewon; Avendaño, María José; Serrano, Eileen F; García-Salum, Tamara; Pardo-Roa, Catalina; Riquelme, Arnoldo; Cai, Yongfei; Renzi, Isabella; Stewart-Jones, Guillaume; Chen, Bing; Medina, Rafael A; Alter, Galit.
  • Bartsch YC; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02138, USA.
  • Tong X; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02138, USA.
  • Kang J; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02138, USA.
  • Avendaño MJ; Department of Pediatric Infectious Diseases and Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
  • Serrano EF; Department of Pediatric Infectious Diseases and Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
  • García-Salum T; Department of Pediatric Infectious Diseases and Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
  • Pardo-Roa C; Advanced Interdisciplinary Rehabilitation Register (AIRR)-COVID-19 Working Group, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
  • Riquelme A; Department of Pediatric Infectious Diseases and Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
  • Cai Y; Advanced Interdisciplinary Rehabilitation Register (AIRR)-COVID-19 Working Group, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
  • Renzi I; Advanced Interdisciplinary Rehabilitation Register (AIRR)-COVID-19 Working Group, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
  • Stewart-Jones G; Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
  • Chen B; Department of Health Sciences, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
  • Medina RA; Division of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Alter G; Moderna Inc., Cambridge, MA 02138, USA.
Sci Transl Med ; 14(642): eabn9243, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1741565
ABSTRACT
The Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or infection. Despite the global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc effector mechanisms. Here, we probed the ability of vaccine-induced antibodies to drive Fc effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant receptor binding domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of RBD-specific antibody Fcγ receptor (FcγR) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific FcγR2a and FcγR3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein-specific antibodies exhibited persistent but reduced binding to FcγRs across all three vaccines, although higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of FcγR2a and FcγR3a binding antibodies and maintenance of Spike protein-specific antibody-dependent natural killer cell activation. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein-specific antibodies continue to drive Fc effector functions, suggesting a capacity for extraneutralizing antibodies to contribute to disease control.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Vaccines / COVID-19 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Sci Transl Med Journal subject: Science / Medicine Year: 2022 Document Type: Article Affiliation country: Scitranslmed.abn9243

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Vaccines / COVID-19 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Sci Transl Med Journal subject: Science / Medicine Year: 2022 Document Type: Article Affiliation country: Scitranslmed.abn9243