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
Citations
More filters
Journal ArticleDOI
Robust induction of functional humoral response by a plant-derived Coronavirus-like particle vaccine candidate for COVID-19
Paulina Kaplonek,Deniz Cizmeci,Jessica S Lee,Sally Shin,Stephanie Fischinger,Philipe Gobeil,Stéphane Pillet,Nathalie Charland,Brian J. Ward,Galit Alter +9 more
TL;DR: In this article , the functional humoral response induced by two doses of CoVLP vaccine candidate from the phase 1 clinical trial, at peak immunogenicity and six months post-vaccination was profiled.
Journal ArticleDOI
SARS-CoV-2 S Glycoprotein Stabilization Strategies
TL;DR: In this article , a review of the structure-based approaches for stabilizing S-CoV-2 S glycoprotein trimers is presented, highlighting the benefits of employing stabilized S trimers versus non-stabilized S in vaccines with respect to their protective efficacy.
Journal ArticleDOI
Recombinant Protein Vaccines against Human Betacoronaviruses: Strategies, Approaches and Progress
Angelina O Kovalenko,Ekaterina M. Ryabchevskaya,Ekaterina A. Evtushenko,Nikolai Nikitin,Olga Karpova +4 more
TL;DR: In this article , the authors summarize the information on the designing of vaccines based on recombinant proteins against highly pathogenic human betacoronaviruses SARS-CoV, MERS-coV, and SARS CoV-2.
Posted ContentDOI
A recombinant SARS-CoV-2 RBD antigen expressed in insect cells elicits immunogenicity and confirms safety in animal models
Ricardo Choque-Guevara,Astrid Poma-Acevedo,Ricardo Montesinos-Millan,Dora Rios-Matos,Kristel Gutierrez-Manchay,Angela Montalvan,Stefany Quinones-Garcia,Maria de Grecia Cauti-Mendoza,Andres Agurto-Arteaga,Ingrid Ramirez-Ortiz,Manuel Criollo-Orozco,Edison Huaccachi-Gonzales,Yomara K. Romero Lazaro,Norma Perez-Martinez,Gisela Isasi-Rivas,Yacory Sernaque-Aguilar,Doris Villanueva-Perez,Katherine Vallejos-Sánchez,Manolo Fernández-Sánchez,Luis Raez Guevara,Manolo Fernández-Díaz,Mirko Zimic +21 more
TL;DR: In this paper, the immunological and safety evaluation in mice and hamsters of a subunit vaccine based on the RBD sub-domain with two adjuvants of oil origin is described.
Journal ArticleDOI
Structural position vectors and symmetries in complex networks.
TL;DR: This work articulate a conceptually appealing and computationally extremely efficient approach to finding and characterizing all symmetric nodes by introducing a structural position vector (SPV) for each node in networks, and argues that the SPV method is generally effective for finding the asymmetric nodes in real-world networks that typically do not have a dominant regular component.
References
More filters
Journal ArticleDOI
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.
Alexandra C. Walls,Young-Jun Park,M. Alejandra Tortorici,M. Alejandra Tortorici,Abigail Wall,Andrew T. McGuire,Andrew T. McGuire,David Veesler +7 more
TL;DR: It is demonstrating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination, and it is shown that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of Sars- coV- 2 S and SARS S bind with similar affinities to human ACE2, correlating with the efficient spread of SATS among humans.
Journal ArticleDOI
Virological assessment of hospitalized patients with COVID-2019.
Roman Wölfel,Victor M. Corman,Wolfgang Guggemos,M Seilmaier,Sabine Zange,Marcel A. Müller,Daniela Niemeyer,Terry Jones,Terry Jones,Patrick Vollmar,Camilla Rothe,Michael Hoelscher,Tobias Bleicker,Sebastian Brünink,Julia Schneider,Rosina Ehmann,Katrin Zwirglmaier,Christian Drosten,Clemens M. Wendtner +18 more
TL;DR: Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.
Journal ArticleDOI
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.
Merryn Voysey,Clemens Sac.,Shabir A. Madhi,Lily Yin Weckx,P M Folegatti,Parvinder K. Aley,Brian Angus,Vicky L. Baillie,Shaun Barnabas,Q E Bhorat,S Bibi,Carmen Briner,P Cicconi,Andrea M. Collins,R Colin-Jones,Clare L. Cutland,Thomas C. Darton,Keertan Dheda,Duncan Cja.,Emary Krw.,Katie J. Ewer,Lee Fairlie,Saul N. Faust,Shuo Feng,Daniela M. Ferreira,Adam Finn,Anna Goodman,Catherine M. Green,Christopher A Green,Paul T. Heath,Christopher Hill,Helen Hill,Ian Hirsch,Hodgson Shc.,Allen Izu,S Jackson,D Jenkin,Joe Ccd.,S Kerridge,Anthonet Koen,Gaurav Kwatra,Rajeka Lazarus,Alison M. Lawrie,A Lelliott,Vincenzo Libri,Patrick J. Lillie,R Mallory,Mendes Ava.,Eveline Pipolo Milan,Angela M. Minassian,Alastair McGregor,Hazel Morrison,Y Mujadidi,Amit J Nana,P J O’Reilly,S D Padayachee,A Pittella,E Plested,Katrina M Pollock,M N Ramasamy,S Rhead,Alexandre Vargas Schwarzbold,Nisha Singh,Andrew Smith,R Song,Matthew D. Snape,Eduardo Sprinz,Rebecca K. Sutherland,R Tarrant,E. Thomson,M E Török,Mark Toshner,Turner Dpj.,Johan Vekemans,Tonya Villafana,Watson Mee.,C J Williams,Alexander D. Douglas,Hill Avs.,Teresa Lambe,Sarah C. Gilbert,Andrew J. Pollard +81 more
TL;DR: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.
Journal ArticleDOI
Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates.
Edward E. Walsh,Robert W. Frenck,Ann R. Falsey,Ann R. Falsey,Nicholas Kitchin,Judith Absalon,Alejandra Gurtman,Stephen Lockhart,Kathleen M. Neuzil,Mark J. Mulligan,Ruth Bailey,Kena A. Swanson,Ping Li,Kenneth Koury,Warren Kalina,David A. Cooper,Camila R. Fontes-Garfias,Pei Yong Shi,Özlem Türeci,Tompkins Kristin Rachael,Kirsten E. Lyke,Vanessa Raabe,Philip R. Dormitzer,Kathrin U. Jansen,Ugur Sahin,William C. Gruber +25 more
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.
Related Papers (5)
Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses.
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine.
Fernando P. Polack,Stephen J. Thomas,Nicholas Kitchin,Judith Absalon,Alejandra Gurtman,Stephen Lockhart,John L. Perez,Gonzalo Pérez Marc,Edson D. Moreira,Cristiano Zerbini,Ruth Bailey,Kena A. Swanson,Satrajit Roychoudhury,Kenneth Koury,Ping Li,Warren Kalina,David A. Cooper,Robert W. Frenck,Laura L. Hammitt,Özlem Türeci,Haylene Nell,Axel Schaefer,Serhat Ünal,Dina B. Tresnan,Susan Mather,Philip R. Dormitzer,Ugur Sahin,Kathrin U. Jansen,William C. Gruber +28 more
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more