Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines
| العنوان: | Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines |
|---|---|
| المؤلفون: | Bali Pulendran, Allison J. Greaney, Max Johnson, Brooke Fiala, Ralph S. Baric, Jesse D. Bloom, Tyler N. Starr, Elizabeth Kepl, Rashmi Ravichandran, David Veesler, Roland Tisch, Mary-Jane Navarro, Kenneth A. Rogers, Kaitlin R. Sprouse, Kelly D. Smith, Natalie Brunette, Megan A. O'Connor, M. Alejandra Tortorici, Douglas E. Ferrell, Davide Corti, Prabhu S. Arunachalam, Timothy P. Sheahan, Samuel Wrenn, Robbert van der Most, Sarah R. Leist, Lisa Shirreff, Harry Kleanthous, Marcos C. Miranda, Alyssa Blackstone, Claire Sydeman, Francois Villinger, Jason S. McLellan, Deleah Pettie, David R. Martinez, Cassandra Ogohara, Minh N. Pham, Lauren Carter, Wesley C. Van Voorhis, Deborah H. Fuller, Samantha K Zepeda, Alexandra Schäfer, Sasha W Tilles, Matthew Clark, Alexandra C. Walls, Rino Rappuoli, John E. Bowen, Neil P. King, Derek T. O'Hagan, Ching-Lin Hsieh |
| المصدر: | Cell bioRxiv article-version (status) pre article-version (number) 1 |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 2019-20 coronavirus outbreak, Immunogen, Coronavirus disease 2019 (COVID-19), biology, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), fungi, Mutant, Antibody titer, COVID-19, Virology, General Biochemistry, Genetics and Molecular Biology, Article, Neutralization, Immunization, Antigen, Polyclonal antibodies, Immunity, vaccine design, biology.protein, receptor-binding domain, Antibody, spike glycoprotein |
| الوصف: | Understanding vaccine-elicited protection against SARS-CoV-2 variants and other sarbecoviruses is key for guiding public health policies. We show that a clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle vaccine (RBD-NP) protects mice from SARS-CoV-2 challenge after a single immunization, indicating a potential dose-sparing strategy. We benchmarked serum neutralizing activity elicited by RBD-NP in non-human primates against a lead prefusion-stabilized SARS-CoV-2 spike (HexaPro) using a panel of circulating mutants. Polyclonal antibodies elicited by both vaccines are similarly resilient to many RBD residue substitutions tested although mutations at and surrounding position 484 have negative consequences for neutralization. Mosaic and cocktail nanoparticle immunogens displaying multiple sarbecovirus RBDs elicit broad neutralizing activity in mice and protect mice against SARS-CoV challenge even in the absence of SARS-CoV RBD in the vaccine. This study provides proof of principle that multivalent sarbecovirus RBD-NPs induce heterotypic protection and motivates advancing such broadly protective sarbecovirus vaccines to the clinic. A clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle vaccine (RBD-NP) is protective in mice after a single immunization and elicits strong antibody responses across circulating mutants and broader sarbecoviruses. Multivalent sarbecovirus RBD-NPs can heterotypic protection as serve as a broad therapeutic against coronaviruses. |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::98c5d8df56cfa58183e50431d4e430baTest https://pubmed.ncbi.nlm.nih.gov/34619077Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....98c5d8df56cfa58183e50431d4e430ba |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |