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An adjuvanted SARS-CoV-2 RBD nanoparticle elicits neutralizing antibodies and fully protective immunity in aged mice
Francesco Borriello; Etsuro Nanishi; Hyuk-Soo Seo; Timothy R. OMeara; Marisa E. McGrath; Yoshine Saito; Robert E. Haupt; Jing Chen; Joann Diray-Arce; Kijun Song; Andrew Z Xu; Timothy M. Caradonna; Jared Feldman; Blake M. Hauser; Aaron G. Schmidt; Robert K. Ernst; Carly Dillen; Stuart M. Weston; Robert M. Johnson; Holly L. Hammond; Jingyou Yu; Aiquan Chang; Luuk Hilgers; Peter Paul Platenburg; Sirano Dhe-Paganon; Dan H. Barouch; Al Ozonoff; Ivan Zanoni; Matthew B. Frieman; David J. Dowling; Ofer Levy.
Afiliação
  • Francesco Borriello; Division of Immunology, Boston Childrens Hospital
  • Etsuro Nanishi; Precision Vaccines Program, Division of Infectious Diseases, Boston Childrens Hospital
  • Hyuk-Soo Seo; Department of Cancer Biology, Dana-Farber Cancer Institute
  • Timothy R. OMeara; Precision Vaccines Program, Division of Infectious Diseases, Boston Childrens Hospital
  • Marisa E. McGrath; Department of Microbiology and Immunology, University of Maryland School of Medicine
  • Yoshine Saito; Precision Vaccines Program, Division of Infectious Diseases, Boston Childrens Hospital
  • Robert E. Haupt; Department of Microbiology and Immunology, University of Maryland School of Medicine
  • Jing Chen; Research Computing Group, Boston Childrens Hospital
  • Joann Diray-Arce; Precision Vaccines Program, Division of Infectious Diseases, Boston Childrens Hospital
  • Kijun Song; Department of Cancer Biology, Dana-Farber Cancer Institute
  • Andrew Z Xu; Department of Cancer Biology, Dana-Farber Cancer Institute
  • Timothy M. Caradonna; Ragon Institute of MGH, MIT, and Harvard
  • Jared Feldman; Ragon Institute of MGH, MIT, and Harvard
  • Blake M. Hauser; Ragon Institute of MGH, MIT, and Harvard
  • Aaron G. Schmidt; Ragon Institute of MGH, MIT, and Harvard
  • Robert K. Ernst; Department of Microbial Pathogenesis, University of Maryland School of Dentistry
  • Carly Dillen; Department of Microbiology and Immunology, University of Maryland School of Medicine
  • Stuart M. Weston; Department of Microbiology and Immunology, University of Maryland School of Medicine
  • Robert M. Johnson; Department of Microbiology and Immunology, University of Maryland School of Medicine
  • Holly L. Hammond; Department of Microbiology and Immunology, University of Maryland School of Medicine
  • Jingyou Yu; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
  • Aiquan Chang; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
  • Luuk Hilgers; LiteVax B.V.
  • Peter Paul Platenburg; LiteVax B.V.
  • Sirano Dhe-Paganon; Department of Cancer Biology, Dana-Farber Cancer Institute
  • Dan H. Barouch; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
  • Al Ozonoff; Precision Vaccines Program, Division of Infectious Diseases, Boston Childrens Hospital
  • Ivan Zanoni; Division of Immunology, Boston Childrens Hospital
  • Matthew B. Frieman; Department of Microbiology and Immunology, University of Maryland School of Medicine
  • David J. Dowling; Precision Vaccines Program, Division of Infectious Diseases, Boston Childrens Hospital
  • Ofer Levy; Precision Vaccines Program, Division of Infectious Diseases, Boston Childrens Hospital
Preprint em En | PREPRINT-BIORXIV | ID: ppbiorxiv-459664
ABSTRACT
Development of affordable and effective vaccines that can also protect vulnerable populations such as the elderly from COVID-19-related morbidity and mortality is a public health priority. Here we took a systematic and iterative approach by testing several SARS-CoV-2 protein antigens and adjuvants to identify a combination that elicits neutralizing antibodies and protection in young and aged mice. In particular, SARS-CoV-2 receptorbinding domain (RBD) displayed as a protein nanoparticle (RBD-NP) was a highly effective antigen, and when formulated with an oil-in-water emulsion containing Carbohydrate fatty acid MonoSulphate derivative (CMS) induced the highest levels of cross-neutralizing antibodies compared to other oil-in-water emulsions or AS01B. Mechanistically, CMS induced antigen retention in the draining lymph node (dLN) and expression of cytokines, chemokines and type I interferon-stimulated genes at both injection site and dLN. Overall, CMSRBD-NP is effective across multiple age groups and is an exemplar of a SARS-CoV-2 subunit vaccine tailored to the elderly.
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Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Tipo de estudo: Experimental_studies / Rct / Systematic_reviews Idioma: En Ano de publicação: 2021 Tipo de documento: Preprint
Texto completo
Adicionar na Minha BVS
Imprimir
XML
Buscar no Google
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Tipo de estudo: Experimental_studies / Rct / Systematic_reviews Idioma: En Ano de publicação: 2021 Tipo de documento: Preprint