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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The Influence of Adjuvant Type on the Immunogenicity of RBD/N Cocktail Antigens as a Vaccine Candidate against SARS-CoV-2 Virus
Gabriela Brzuska,Marta Zimna,Klaudia Baranska,Boguslaw Szewczyk,Petra Straková,Daniel Růžek,Ewelina Król +6 more
TL;DR: In this article , the effect of adjuvants on the immunogenicity of RBD/N SARS-CoV-2 cocktail proteins was studied and the results showed that immunization with both antigens plus the different adjvants studied elicited higher Th1 and Th2 responses against RBD and N, which contributed to higher neutralization of the virus.
Journal ArticleDOI
Precision Vaccinology Approaches for the Development of Adjuvanted Vaccines Targeted to Distinct Vulnerable Populations
TL;DR: In this paper , the authors focus on two key elements of precision vaccinology, as applied to epidemic/pandemic response and preparedness, including selecting robust combinations of adjuvants and antigens, and coupling these platforms with appropriate formulation systems.
Journal ArticleDOI
What Can De Novo Protein Design Bring to the Treatment of Hematological Disorders?
Abstract: Simple Summary Because of the seriousness and complexity of hematological disorders, it is particularly critical to develop new methods for treating them. A protein engineering technique has been used to further enhance therapeutic effects and minimize side effects of protein-based therapeutics. However, the essence of the protein engineering technique is to modify and/or ameliorate natural existing proteins. In recent years, de novo proteins have been developed at a high speed, and their applications in the biomedical field are increasing, including in developing novel diagnostic and therapeutic drugs, novel vaccine techniques, and novel biological materials. At the same time, de novo proteins have also been applied to improve the efficacy of treatment methods in hematological disorders, such as designing the novel structures of chimeric antigen receptors, new inhibitors for treating chronic myeloid leukemia, and the novel type of interleukin-2. Therefore, the purpose of our review is to summarize the recent development of de novo protein design and its application in biomedicine, especially in exploring new treatment methods for hematological disorders. Abstract Protein therapeutics have been widely used to treat hematological disorders. With the advent of de novo protein design, protein therapeutics are not limited to ameliorating natural proteins but also produce novel protein sequences, folds, and functions with shapes and functions customized to bind to the therapeutic targets. De novo protein techniques have been widely used biomedically to design novel diagnostic and therapeutic drugs, novel vaccines, and novel biological materials. In addition, de novo protein design has provided new options for treating hematological disorders. Scientists have designed protein switches called Colocalization-dependent Latching Orthogonal Cage–Key pRoteins (Co-LOCKR) that perform computations on the surface of cells. De novo designed molecules exhibit a better capacity than the currently available tyrosine kinase inhibitors in chronic myeloid leukemia therapy. De novo designed protein neoleukin-2/15 enhances chimeric antigen receptor T-cell activity. This new technique has great biomedical potential, especially in exploring new treatment methods for hematological disorders. This review discusses the development of de novo protein design and its biological applications, with emphasis on the treatment of hematological disorders.
Journal ArticleDOI
Structure-based design of oligomeric receptor-binding domain (RBD) recombinant proteins as potent vaccine candidates against SARS-CoV-2
TL;DR: In this article , a single-chain dimer derived from Wuhan-Hu-1 was fused with a trimerization motif, and a cysteine was also introduced at the C-terminus, and the resultant recombinant protein 2RBDpLC was expressed in Sf9 cells using a baculovirus expression system.
Journal ArticleDOI
Pre-clinical models to define correlates of protection for SARS-CoV-2
TL;DR: In this article , the authors focus on the advantages of the use of animal models for the definition of CoPs, with particular attention on their application in the search for SARS-CoV-2 CoPs.
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TL;DR: The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation.
Journal ArticleDOI
The Architecture of SARS-CoV-2 Transcriptome.
TL;DR: Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to the understanding of the life cycle and pathogenicity of SARS-CoV-2.
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