Three immunizations with Novavax’s protein vaccines increase antibody breadth and provide durable protection from SARS-CoV-2
Klara Lenart,
Rodrigo Arcoverde Cerveira,
Fredrika Hellgren,
Sebastian Ols,
Daniel J. Sheward,
Changil Kim,
Alberto Cagigi,
Matthew Gagne,
Brandon Davis,
Daritza Germosen,
Vicky Roy,
Galit Alter,
Hélène Letscher,
Jérôme Van Wassenhove,
Wesley Gros,
Anne-Sophie Gallouët,
Roger Le Grand,
Harry Kleanthous,
Mimi Guebre-Xabier,
Ben Murrell,
Nita Patel,
Gregory Glenn,
Gale Smith,
Karin Loré
Affiliations
Klara Lenart
Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet
Rodrigo Arcoverde Cerveira
Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet
Fredrika Hellgren
Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet
Sebastian Ols
Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet
Daniel J. Sheward
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
Changil Kim
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
Alberto Cagigi
Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet
Matthew Gagne
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Brandon Davis
Ragon Institute of MGH, MIT, and Harvard
Daritza Germosen
Ragon Institute of MGH, MIT, and Harvard
Vicky Roy
Ragon Institute of MGH, MIT, and Harvard
Galit Alter
Ragon Institute of MGH, MIT, and Harvard
Hélène Letscher
Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre
Jérôme Van Wassenhove
Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre
Wesley Gros
Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre
Anne-Sophie Gallouët
Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre
Roger Le Grand
Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre
Harry Kleanthous
Bill & Melinda Gates Foundation
Mimi Guebre-Xabier
Novavax Inc
Ben Murrell
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
Nita Patel
Novavax Inc
Gregory Glenn
Novavax Inc
Gale Smith
Novavax Inc
Karin Loré
Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet
Abstract The immune responses to Novavax’s licensed NVX-CoV2373 nanoparticle Spike protein vaccine against SARS-CoV-2 remain incompletely understood. Here, we show in rhesus macaques that immunization with Matrix-MTM adjuvanted vaccines predominantly elicits immune events in local tissues with little spillover to the periphery. A third dose of an updated vaccine based on the Gamma (P.1) variant 7 months after two immunizations with licensed NVX-CoV2373 resulted in significant enhancement of anti-spike antibody titers and antibody breadth including neutralization of forward drift Omicron variants. The third immunization expanded the Spike-specific memory B cell pool, induced significant somatic hypermutation, and increased serum antibody avidity, indicating considerable affinity maturation. Seven months after immunization, vaccinated animals controlled infection by either WA-1 or P.1 strain, mediated by rapid anamnestic antibody and T cell responses in the lungs. In conclusion, a third immunization with an adjuvanted, low-dose recombinant protein vaccine significantly improved the quality of B cell responses, enhanced antibody breadth, and provided durable protection against SARS-CoV-2 challenge.
