Frontiers in Immunology (Mar 2023)

Convalescent human IgG, but not IgM, from COVID-19 survivors confers dose-dependent protection against SARS-CoV-2 replication and disease in hamsters

  • Hannah A. D. King,
  • Hannah A. D. King,
  • Hannah A. D. King,
  • Vincent Dussupt,
  • Vincent Dussupt,
  • Vincent Dussupt,
  • Letzibeth Mendez-Rivera,
  • Letzibeth Mendez-Rivera,
  • Letzibeth Mendez-Rivera,
  • Bonnie M. Slike,
  • Bonnie M. Slike,
  • Bonnie M. Slike,
  • Ursula Tran,
  • Ursula Tran,
  • Ursula Tran,
  • Nathan D. Jackson,
  • Nathan D. Jackson,
  • Nathan D. Jackson,
  • Erica Barkei,
  • Michelle Zemil,
  • Michelle Zemil,
  • Michelle Zemil,
  • Emily Tourtellott-Fogt,
  • Emily Tourtellott-Fogt,
  • Emily Tourtellott-Fogt,
  • Caitlin H. Kuklis,
  • Sandrine Soman,
  • Aslaa Ahmed,
  • Maciel Porto,
  • Christopher Kitajewski,
  • Brittany Spence,
  • Dalia Benetiene,
  • Lindsay Wieczorek,
  • Lindsay Wieczorek,
  • Lindsay Wieczorek,
  • Swagata Kar,
  • Gregory Gromowski,
  • Victoria R. Polonis,
  • Shelly J. Krebs,
  • Shelly J. Krebs,
  • Shelly J. Krebs,
  • Kayvon Modjarrad,
  • Diane L. Bolton,
  • Diane L. Bolton,
  • Diane L. Bolton

DOI
https://doi.org/10.3389/fimmu.2023.1138629
Journal volume & issue
Vol. 14

Abstract

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IntroductionAntibody therapeutic strategies have served an important role during the COVID-19 pandemic, even as their effectiveness has waned with the emergence of escape variants. Here we sought to determine the concentration of convalescent immunoglobulin required to protect against disease from SARS-CoV-2 in a Syrian golden hamster model.MethodsTotal IgG and IgM were isolated from plasma of SARS-CoV-2 convalescent donors. Dose titrations of IgG and IgM were infused into hamsters 1 day prior to challenge with SARS-CoV-2 Wuhan-1.ResultsThe IgM preparation was found to have ~25-fold greater neutralization potency than IgG. IgG infusion protected hamsters from disease in a dose-dependent manner, with detectable serum neutralizing titers correlating with protection. Despite a higher in vitro neutralizing potency, IgM failed to protect against disease when transferred into hamsters.DiscussionThis study adds to the growing body of literature that demonstrates neutralizing IgG antibodies are important for protection from SARS-CoV-2 disease, and confirms that polyclonal IgG in sera can be an effective preventative strategy if the neutralizing titers are sufficiently high. In the context of new variants, against which existing vaccines or monoclonal antibodies have reduced efficacy, sera from individuals who have recovered from infection with the emerging variant may potentially remain an efficacious tool.

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