Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.
Prabhu S. Arunachalam,Alexandra C. Walls,Nadia A. Golden,Caroline Atyeo,Stephanie Fischinger,Chunfeng Li,Pyone P. Aye,Mary Jane Navarro,Lilin Lai,Venkata Viswanadh Edara,Katharina Röltgen,Kenneth A. Rogers,Lisa Shirreff,Douglas E. Ferrell,Samuel Wrenn,Deleah Pettie,John C. Kraft,Marcos C. Miranda,Elizabeth Kepl,Claire Sydeman,Natalie Brunette,Michael E. P. Murphy,Brooke Fiala,Lauren Carter,Alexander G. White,Meera Trisal,Ching-Lin Hsieh,Kasi E. Russell-Lodrigue,Christopher Monjure,Jason Dufour,Skye Spencer,Lara A. Doyle-Meyers,Rudolph Bohm,Nicholas J. Maness,Chad J. Roy,Jessica A. Plante,Kenneth S. Plante,Alex Lee Zhu,Matthew J. Gorman,Sally Shin,Xiaoying Shen,Jane Fontenot,Shakti Gupta,Derek T. O'Hagan,Robbert van der Most,Rino Rappuoli,Robert L. Coffman,David Novack,Jason S. McLellan,Shankar Subramaniam,David C. Montefiori,Scott D. Boyd,JoAnne L. Flynn,Galit Alter,Francois Villinger,Harry Kleanthous,Jay Rappaport,Mehul S. Suthar,Neil P. King,Neil P. King,David Veesler,Bali Pulendran +61 more
TLDR
In this article, the authors demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses.Abstract:
The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).read more
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SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses
Alexandra C. Walls,Kaitlin R. Sprouse,John E. Bowen,Anshu Joshi,Nicholas Franko,Mary Jane Navarro,Cameron Stewart,Elisabetta Cameroni,Matthew McCallum,Erin A. Goecker,Emily J. Degli-Angeli,Jennifer Logue,Alexander L. Greninger,Davide Corti,Helen Y. Chu,David Veesler +15 more
TL;DR: In this paper , the authors demonstrate that breakthrough infections induce serum-binding and neutralizing antibody responses that are markedly more potent, durable, and resilient to spike mutations observed in variants than those in subjects who received only 2 doses of vaccine.
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Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines
John E. Bowen,Amin Addetia,Ha V. Dang,Cameron Stewart,Jack T Brown,William K Sharkey,Kaitlin R. Sprouse,Alexandra C. Walls,Ignacio Mazzitelli,Jennifer Logue,Nicholas Franko,Nadine Czudnochowski,Abigail E. Powell,Exequiel Dellota,Kumail Ahmed,A. S. Ansari,Elisabetta Cameroni,Andrea Gori,Alessandra Bandera,Christine M. Posavad,Jennifer M. Dan,Zeli Zhang,Daniela Weiskopf,Alessandro Sette,Shane Crotty,Najeeha Talat Iqbal,Davide Corti,Jorge Geffner,Gyorgy Snell,Renata Grifantini,Helen Y. Chu,David Veesler +31 more
TL;DR: It is suggested that although Omicron sublineages evade polyclonal neutralizing antibody responses elicited by primary vaccine series, vaccine boosters may provide sufficient protection against Omicrons-induced severe disease.
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Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry
Young-Jun Park,Anna De Marco,Tyler N. Starr,Zhuoming Li,Dora Pinto,Alexandra C. Walls,Fabrizia Zatta,Samantha K. Zepeda,John E. Bowen,Kaitlin R. Sprouse,Anshu Joshi,Martina Giurdanella,Barbara Guarino,Julia Noack,Rana Abdelnabi,Shi Yan Caroline Foo,Laura E. Rosen,Florian A. Lempp,Fabio Benigni,Gyorgy Snell,Johan Neyts,Sean P. J. Whelan,Herbert W. Virgin,Jesse D. Bloom,Davide Corti,Matteo Samuele Pizzuto,David Veesler +26 more
TL;DR: The isolation and characterization of a human monoclonal antibody, designated S2K146, that broadly neutralizes viruses belonging to SARS-CoV– and SARV-2–related sarbecovirus clades, which use angiotensin-converting enzyme 2 (ACE2) as an entry receptor.
Journal ArticleDOI
Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines.
Alexandra C. Walls,Marcos C. Miranda,Alexandra Schäfer,Minh N. Pham,Allison J. Greaney,Allison J. Greaney,Prabhu S. Arunachalam,Mary-Jane Navarro,M. Alejandra Tortorici,M. Alejandra Tortorici,Kenneth A. Rogers,Megan A. O'Connor,Lisa Shirreff,Douglas E. Ferrell,John E. Bowen,Natalie Brunette,Elizabeth Kepl,Samantha K Zepeda,Tyler N. Starr,Ching-Lin Hsieh,Brooke Fiala,Samuel Wrenn,Deleah Pettie,Claire Sydeman,Kaitlin R. Sprouse,Max Johnson,Alyssa Blackstone,Rashmi Ravichandran,Cassandra Ogohara,Lauren Carter,Sasha W Tilles,Rino Rappuoli,Sarah R. Leist,David R. Martinez,Matthew Clark,Roland Tisch,Derek T. O'Hagan,Robbert van der Most,Wesley C. Van Voorhis,Davide Corti,Jason S. McLellan,Harry Kleanthous,Timothy P. Sheahan,Kelly D. Smith,Deborah H. Fuller,Francois Villinger,Jesse D. Bloom,Jesse D. Bloom,Bali Pulendran,Ralph S. Baric,Neil P. King,David Veesler +51 more
TL;DR: In this paper, a clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle (RBD-NP) vaccine was used to protect mice from SARS CoV 2 challenge after a single immunization.
Journal ArticleDOI
Correlates of protection against SARS‐CoV‐2 infection and COVID‐19 disease
TL;DR: Antibodies against epitopes in S1 give the most accurate CoP against infection by the SARS‐CoV‐2 coronavirus, and the role of cellular responses can be discerned with respect to CD4+ T cells and their augmentation of antibodies, and with regard to control of viral replication.
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