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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A booster dose of mRNA-based COVID-19 vaccines fosters the development of an immune response in immunosuppressed fragile patients.
Elena Azzolini,Clarissa Pozzi,Luca Germagnoli,Bianca Oresta,Nicola Carriglio,Mariella Calleri,Carlo Selmi,Maria De Santis,Sergio Finazzi,Carmelo Carlo-Stella,Alexia Bertuzzi,Fernando Couto Motta,Angela Ceribelli,Alberto Mantovani,F. Bonelli,M. Rescigno +15 more
TL;DR: It is found that fragile patients, depending on the type of treatment, poorly respond to SARS-CoV-2 mRNA vaccines, however, an additional booster dose of vaccine induced a good immune response in almost all of the patients except those receiving anti-CD20 antibody.
Posted ContentDOI
Broad and Durable Humoral Responses Following Single Hydrogel Immunization of SARS-CoV-2 Subunit Vaccine
Ben S. Ou,Olivia Saouaf,Jerry Yan,Theodora U. J. Bruun,Julie Baillet,Neil P. King,Eric A. Appel +6 more
TL;DR: In this paper , a single immunization SARS-CoV-2 subunit vaccine that could rapidly generate potent, broad, and durable humoral immunity was developed, which leveraged injectable polymer-nanoparticle (PNP) hydrogels as a depot technology for the sustained delivery of a nanoparticle COVID antigen displaying multiple copies of the RBD-NP.
Journal ArticleDOI
Single-cell sequencing of PBMC characterizes the altered transcriptomic landscape of classical monocytes in BNT162b2-induced myocarditis
Nahee Hwang,Yun Jeong Huh,Seong-Min Bu,Kyung Jin Seo,S. Kwon,Jae-Woo Kim,Bo Kyung Yoon,Hyo-Suk Ahn,Sungsoon Fang +8 more
TL;DR: The importance of classical monocytes in the pathogenesis of myocarditis following BNT162b2 vaccination is provided for the first time and the possibility that vaccination affects monocytes, further inducing their differentiation and infiltration into the heart is presented.
Journal ArticleDOI
Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice
Etsuro Nanishi,Francesco Borriello,Hyuk-Soo Seo,Timothy O'Meara,Marisa McGrath,Y. Saito,Jing Chen,Joann Diray-Arce,Kijun Song,A. Xu,Soumik Barman,Manisha Menon,Danica Dong,Timothy M. Caradonna,Jared Feldman,Blake M. Hauser,Aaron G. Schmidt,Lindsey R. Baden,Robert K. Ernst,Carly A. Dillen,Jingyou Yu,Aiquan Chang,Luuk A. Th. Hilgers,Peter Paul Platenburg,Sirano Dhe-Paganon,Dan H. Barouch,Al Ozonoff,Ivan Zanoni,Matthew B. Frieman,David J. Dowling,Ofer Levy +30 more
TL;DR: In this paper , an oil-in-water emulsion containing carbohydrate fatty acid monosulphate derivative (CMS:O/W) was used to identify a combination that elicits antibodies and protection in young and aged mice.
Journal ArticleDOI
Systems serology-based comparison of antibody effector functions induced by adjuvanted vaccines to guide vaccine design
TL;DR: In this article , the role of adjuvants in shaping the maturation of antibody effector functions remains under investigated, using systems serology, using adjvants in licensed vaccines (AS01 B /AS01 E /AS03/AS04/Alum) combined with a model antigen.
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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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