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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Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2
Kun Xu,Ping Gao,Sheng Liu,Shuaiyao Lu,W. Lei,Tianyi Zheng,Xueyuan Liu,Yufeng Xie,Zhennan Zhao,Shuxin Guo,Cong Tang,Yun jeong Yang,Wenhai Yu,Junbin Wang,Yanan Zhou,Q. Huang,Chuanyu Liu,Yaling An,Rong Zhang,Yuxuan Han,Minrun Duan,Shao Feng Wang,Chenxi Yang,Changwei Wu,Xiaoya Liu,Guangbiao She,Yan Liu,Xin Zhao,Kehui Xu,Jianxun Qi,Guizhen Wu,Xiaozhong Peng,Lianpan Dai,Peiyi Wang,George F. Gao +34 more
TL;DR: In this paper , a chimeric RBD-dimer vaccine approach was developed to adapt SARS-CoV-2 variants, and the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice.
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Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry
Young-Jun Park,Anna De Marco,Tyler N. Starr,Zhuoming Liu,Dora Pinto,Alexandra C. Walls,Fabrizia Zatta,Samantha K Zepeda,John E. Bowen,Kaitlin S Sprouse,Anshu Joshi,Martina Giurdanella,Barbara Guarino,Julia Noack,Rana Abdelnabi,Shi-Yan Caroline Foo,Florian A. Lempp,Fabio Benigni,Gyorgy Snell,Johan Neyts,Sean P. J. Whelan,Herbert W. Virgin,Jesse D. Bloom,Jesse D. Bloom,Davide Corti,Matteo Samuele Pizzuto,David Veesler +26 more
TL;DR: In this paper, the authors describe the isolation and characterization of a human monoclonal antibody, designated S2K146, broadly neutralizing viruses belonging to all three sarbecovirus clades known to utilize ACE2 as entry receptor and protecting therapeutically against SARS-CoV-2 beta challenge in hamsters.
Journal ArticleDOI
An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice
Etsuro Nanishi,Francesco Borriello,Marisa McGrath,Dmitry Kononov,A. A. Vasil’eva,ALISON MATHEUS DA SILVA ALENCAR,Klaus Lederer +6 more
TL;DR: In this article , an aluminum hydroxide (AH) and CpG adjuvant formulation (AH:CpG) was used to enhance RBD immunogenicity in young and aged mice.
Journal ArticleDOI
A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice, rabbits and NHPs
Zezhong Liu,Jie Zhou,Wei Xu,Wei Deng,Yanqun Wang,Meiyu Wang,Qian Wang,M Hsieh,Jingming Dong,Xinling Wang,Weijin Huang,Lixiao Xing,Miaoling He,Chunlin Tao,Youhua Xie,Yi-Lan Zhang,Youchun Wang,Jincun Zhao,Zhenghong Yuan,Chuan Qin,Shibo Jiang,Lu Lu +21 more
TL;DR: In this article , a new STING agonist, CF501, was used to develop a pan-sarbecovirus vaccine to combat current and future outbreaks of SARS-CoV-2.
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A Summary of the SARS-CoV-2 Vaccines and Technologies Available or under Development
Zainalabideen A. Abdulla,Sharaf M. Al-Bashir,Noor S. Al-Salih,Ala A. Aldamen,Mohammad Z. Abdulazeez +4 more
TL;DR: In this article, the authors reviewed the currently used vaccines in light of the different influencing parameters, including mode of action, dosage protocol, age group of the vaccinee, side effects, storage conditions, mounted immune response, and cost.
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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.
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