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Collaboration between the Fab and Fc contribute to maximal protection against SARS-CoV-2 in nonhuman primates following NVX-CoV2373 subunit vaccine with Matrix-M™ vaccination.
Gorman, Matthew J; Patel, Nita; Guebre-Xabier, Mimi; Zhu, Alex; Atyeo, Caroline; Pullen, Krista M; Loos, Carolin; Goez-Gazi, Yenny; Carrion, Ricardo; Tian, Jing-Hui; Yaun, Dansu; Bowman, Kathryn; Zhou, Bin; Maciejewski, Sonia; McGrath, Marisa E; Logue, James; Frieman, Matthew B; Montefiori, David; Mann, Colin; Schendel, Sharon; Amanat, Fatima; Krammer, Florian; Saphire, Erica Ollmann; Lauffenburger, Douglas; Greene, Ann M; Portnoff, Alyse D; Massare, Michael J; Ellingsworth, Larry; Glenn, Gregory; Smith, Gale; Alter, Galit.
Afiliación
  • Gorman MJ; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Patel N; Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
  • Guebre-Xabier M; Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
  • Zhu A; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Atyeo C; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Pullen KM; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Loos C; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Goez-Gazi Y; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Carrion R; Texas Biomedical Research Institute. 8715 West Military Drive, San Antonio, TX 78227, USA.
  • Tian JH; Texas Biomedical Research Institute. 8715 West Military Drive, San Antonio, TX 78227, USA.
  • Yaun D; Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
  • Bowman K; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Zhou B; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Maciejewski S; Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
  • McGrath ME; Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
  • Logue J; University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD 21201, USA.
  • Frieman MB; University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD 21201, USA.
  • Montefiori D; University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD 21201, USA.
  • Mann C; Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
  • Schendel S; La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Amanat F; La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Saphire EO; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Lauffenburger D; La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Greene AM; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Portnoff AD; Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
  • Massare MJ; Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
  • Ellingsworth L; Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
  • Glenn G; Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
  • Smith G; Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
  • Alter G; Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA.
bioRxiv ; 2021 Feb 05.
Article en En | MEDLINE | ID: mdl-33564763
ABSTRACT
Recently approved vaccines have already shown remarkable protection in limiting SARS-CoV-2 associated disease. However, immunologic mechanism(s) of protection, as well as how boosting alters immunity to wildtype and newly emerging strains, remain incompletely understood. Here we deeply profiled the humoral immune response in a cohort of non-human primates immunized with a stable recombinant full-length SARS-CoV-2 spike (S) glycoprotein (NVX-CoV2373) at two dose levels, administered as a single or two-dose regimen with a saponin-based adjuvant Matrix-M™. While antigen dose had some effect on Fc-effector profiles, both antigen dose and boosting significantly altered overall titers, neutralization and Fc-effector profiles, driving unique vaccine-induced antibody fingerprints. Combined differences in antibody effector functions and neutralization were strongly associated with distinct levels of protection in the upper and lower respiratory tract, pointing to the presence of combined, but distinct, compartment-specific neutralization and Fc-mechanisms as key determinants of protective immunity against infection. Moreover, NVX-CoV2373 elicited antibodies functionally target emerging SARS-CoV-2 variants, collectively pointing to the critical collaborative role for Fab and Fc in driving maximal protection against SARS-CoV-2. Collectively, the data presented here suggest that a single dose may prevent disease, but that two doses may be essential to block further transmission of SARS-CoV-2 and emerging variants. HIGHLIGHTS NVX-CoV2373 subunit vaccine elicits receptor blocking, virus neutralizing antibodies, and Fc-effector functional antibodies.The vaccine protects against respiratory tract infection and virus shedding in non-human primates (NHPs).Both neutralizing and Fc-effector functions contribute to protection, potentially through different mechanisms in the upper and lower respiratory tract.Both macaque and human vaccine-induced antibodies exhibit altered Fc-receptor binding to emerging mutants.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos