Dynamics of SARS-CoV-2 VOC Neutralization and Novel mAb Reveal Protection against Omicron
Linhui Hao,
Tien-Ying Hsiang,
Ronit R. Dalmat,
Renee Ireton,
Jennifer F. Morton,
Caleb Stokes,
Jason Netland,
Malika Hale,
Chris Thouvenel,
Anna Wald,
Nicholas M. Franko,
Kristen Huden,
Helen Y. Chu,
Alex Sigal,
Alex L. Greninger,
Sasha Tilles,
Lynn K. Barrett,
Wesley C. Van Voorhis,
Jennifer Munt,
Trevor Scobey,
Ralph S. Baric,
David J. Rawlings,
Marion Pepper,
Paul K. Drain,
Michael Gale
Affiliations
Linhui Hao
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA
Tien-Ying Hsiang
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA
Ronit R. Dalmat
International Clinical Research Center, Department of Global Health, Schools of Medicine and Public Health, University of Washington, Seattle, WA 98104, USA
Renee Ireton
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA
Jennifer F. Morton
International Clinical Research Center, Department of Global Health, Schools of Medicine and Public Health, University of Washington, Seattle, WA 98104, USA
Caleb Stokes
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA
Jason Netland
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA
Malika Hale
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA
Chris Thouvenel
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA
Anna Wald
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA 98195, USA
Nicholas M. Franko
Division of Allergy and Infectious Diseases, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA
Kristen Huden
Division of Allergy and Infectious Diseases, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA
Helen Y. Chu
Division of Allergy and Infectious Diseases, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA
Alex Sigal
Africa Health Research Institute, Durban 4001, South Africa
Alex L. Greninger
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA
Sasha Tilles
Center for Emerging & Re-Emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA
Lynn K. Barrett
Center for Emerging & Re-Emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA
Wesley C. Van Voorhis
Center for Emerging & Re-Emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA
Jennifer Munt
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27695, USA
Trevor Scobey
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27695, USA
Ralph S. Baric
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27695, USA
David J. Rawlings
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA
Marion Pepper
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA
Paul K. Drain
International Clinical Research Center, Department of Global Health, Schools of Medicine and Public Health, University of Washington, Seattle, WA 98104, USA
Michael Gale
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA
New variants of SARS-CoV-2 continue to emerge and evade immunity. We isolated SARS-CoV-2 temporally across the pandemic starting with the first emergence of the virus in the western hemisphere and evaluated the immune escape among variants. A clinic-to-lab viral isolation and characterization pipeline was established to rapidly isolate, sequence, and characterize SARS-CoV-2 variants. A virus neutralization assay was applied to quantitate humoral immunity from infection and/or vaccination. A panel of novel monoclonal antibodies was evaluated for antiviral efficacy. We directly compared all variants, showing that convalescence greater than 5 months post-symptom onset from ancestral virus provides little protection against SARS-CoV-2 variants. Vaccination enhances immunity against viral variants, except for Omicron BA.1, while a three-dose vaccine regimen provides over 50-fold enhanced protection against Omicron BA.1 compared to a two-dose. A novel Mab neutralizes Omicron BA.1 and BA.2 variants better than the clinically approved Mabs, although neither can neutralize Omicron BA.4 or BA.5. Thus, the need remains for continued vaccination-booster efforts, with innovation for vaccine and Mab improvement for broadly neutralizing activity. The usefulness of specific Mab applications links with the window of clinical opportunity when a cognate viral variant is present in the infected population.
