| Autor: |
Zimmerman O; Department of Medicine, and., Altman Doss AM; Department of Pediatrics, Washington University in St. Louis, St. Louis, Missouri, USA., Ying B; Department of Medicine, and., Liang CY; Department of Pathology and Immunology., Mackin SR; Department of Pathology and Immunology., Davis-Adams HG; Department of Medicine, and., Adams LJ; Department of Pathology and Immunology., VanBlargan LA; Department of Medicine, and., Chen RE; Department of Pathology and Immunology., Scheaffer SM; Department of Medicine, and., Desai P; Department of Medicine, and., Raju S; Department of Pathology and Immunology., Mantia TL; Department of Medicine, and., O'Shaughnessy CC; Department of Medicine, and., Monroy JM; Department of Medicine, and., Wedner HJ; Department of Medicine, and., Rigell CJ; Department of Medicine, and., Kau AL; Department of Medicine, and.; Department of Molecular Microbiology.; Center for Women's Infectious Disease Research., Dy TB; Department of Medicine, and., Ren Z; Department of Medicine, and., Turner JS; Department of Pathology and Immunology., O'Halloran JA; Department of Medicine, and., Presti RM; Department of Medicine, and.; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, and.; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, Missouri, USA., Kendall PL; Department of Medicine, and., Fremont DH; Department of Pathology and Immunology., Ellebedy AH; Department of Pathology and Immunology.; Department of Molecular Microbiology.; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, and.; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, Missouri, USA., Diamond MS; Department of Medicine, and.; Department of Pathology and Immunology.; Department of Molecular Microbiology.; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, and.; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, Missouri, USA. |
| Abstrakt: |
Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022. We show that prepandemic IG had no appreciable cross-reactivity or neutralizing activity against SARS-CoV-2. Anti-spike antibody titers and neutralizing activity against SARS-CoV-2 WA1/2020 D614G increased gradually after the pandemic started and reached levels comparable to vaccinated healthy donors 18 months after the diagnosis of the first COVID-19 case in the United States in January 2020. The average time between production to infusion of IG products was 8 months, which resulted in poor neutralization of the variant strain circulating at the time of infusion. Despite limited neutralizing activity, IG prophylaxis with clinically relevant dosing protected susceptible K18-hACE2-transgenic mice against clinical disease, lung infection, and lung inflammation caused by the XBB.1.5 Omicron variant. Moreover, following IG prophylaxis, levels of XBB.1.5 infection in the lung were higher in FcγR-KO mice than in WT mice. Thus, IG replacement products with poor neutralizing activity against evolving SARS-CoV-2 variants likely confer protection to patients with immune deficiency disorders through Fc effector function mechanisms. |
