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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Squalene in oil-based adjuvant improves the immunogenicity of SARS-CoV-2 RBD and confirms safety in animal models
Ricardo Choque-Guevara,Astrid Poma-Acevedo,Ricardo Montesinos-Millan,Dora Rios-Matos,Kristel Gutierrez-Manchay,A. Montalvan-Avalos,Stefany Quiñones-Garcia,Maria de Grecia Cauti-Mendoza,Andres Agurto-Arteaga,I. Ramírez-Ortiz,Manuel Criollo-Orozco,Edison Huaccachi-Gonzales,Yomara K. Romero,Norma Perez-Martinez,Gisela Isasi-Rivas,Yacory Sernaque-Aguilar,D. Villanueva-Perez,Freddy Ygnacio,Katherine Vallejos-Sánchez,Manolo Fernández-Sánchez,Luis Guevara-Sarmiento,Manolo Fernández-Díaz,Mirko Zimic +22 more
TL;DR: The results have shown the potential of this formulation vaccine to be evaluated in a challenge against SARS-CoV-2 and determine its ability to confer protection and was shown to be safe, as demonstrated by the histopathological analysis in lungs, liver and kidney.
Journal ArticleDOI
A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates
Payton A. Weidenbacher,Mrinmoy Sanyal,Natalia Friedland,Shaogeng Tang,Prabhu S. Arunachalam,Mengyun Hu,Ozan S. Kumru,Mary Kate Morris,Jane Fontenot,Lisa Shirreff,J. Do,Ya-Chen Cheng,Gayathri Vasudevan,Mark B. Feinberg,Francois Villinger,Carly Hanson,Sangeeta B. Joshi,David B. Volkin,Bali Pulendran,Peter S. Kim +19 more
TL;DR: DCFHP-alum as discussed by the authors is a protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant, elicits potent and durable neutralizing antisera in non-human primates against known VOCs including Omicron BQ.
Journal ArticleDOI
A receptor-binding domain-based nanoparticle vaccine elicits durable neutralizing antibody responses against SARS-CoV-2 and variants of concern
I-Jung Lee,Yu-Hua Lan,Ping-Yi Wu,Yan‐Wei Wu,Yu‐Hung Chen,Sheng Che Tseng,Tzu-Jiun Kuo,Cheng-Pu Sun,Jia-Tsrong Jan,Hsiu-Hua Ma,Chun-Che Liao,Jiangli Liang,Hui Ying Ko,Chih-Shin Chang,Wen-Chun Liu,Yi An Ko,Yen-Hui Chen,Zong Lin Sie,Szu-I Tsung,Yi-Ling Lin,I-Hsuan Wang,Mi-Hua Tao +21 more
TL;DR: Wang et al. as mentioned in this paper developed a subunit vaccine, ASD254, by using a nanoparticle vaccine platform to encapsulate the SARS-CoV-2 spike receptor-binding domain (RBD) protein.
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Novel skewed usage of B-cell receptors in COVID-19 patients with various clinical presentations
Junpeng Ma,Han Bai,Tian Gong,Weikang Mao,Yijun Nie,Xuan-Ming Zhang,Yanyan Da,Xiaorui Wang,Hongyu Qi,Qiqi Zeng,Fang Hu,Xin Qi,Bingyin Shi,Chengsheng Zhang +13 more
TL;DR: In this article , single-cell B cell receptor sequencing (scBCR-seq) of the PBMC samples from eleven healthy controls, five asymptomatic subjects and 33 symptomatic COVID-19 patients with various clinical presentations, and subsequently analyzed the abundance and diversity of the BCR repertoires in different groups, respectively.
Posted ContentDOI
Distinct sensitivities to SARS-CoV-2 variants in vaccinated humans and mice
TL;DR: This article showed that vaccinated BALB/c mice do not recapitulate faithfully the breadth and potency of neutralizing antibody responses against emerging SARS-CoV-2 variants of concern, as compared to non-human primates or humans.
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