1. Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity
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Robert Dagil, Gorben P. Pijlman, Søren R. Paludan, Susan Thrane, Anette Strøbæk, Tim J. Dalebout, Blanka W. Nalewajek, Tanja Domeyer, Laura F. Andersson, Sebenzile K. Myeni, Susheel K. Singh, Anette Stryhn Buus, Michael Theisen, Vladislav Soroka, Thomas M. Hulen, Søren Buus, Emma W. Horsted, Stine B. Clemmensen, Thor G. Theander, Laurits Fredsgaard, Cyrielle Fougeroux, Magdalena Skrzypczak, Ali Salanti, Benjamin Mordmüller, Manja Idorn, Louise Goksøyr, Kasper Iversen, Max Søgaard, Jerzy Dorosz, Asier Garcia-Senosiain, Sayit Mahmut Erdoğan, Line S. Reinert, Tobias Gustavsson, Morten Nielsen, Lene Holm Harritshøj, Bettina Hierzberger, Marjolein Kikkert, Henrik Ullum, Paul Khalifé, Swati Choudhary, Adam F. Sander, Kara Lee Aves, Christoph M. Janitzek, Willem A. de Jongh, Elena Ethel Vidal-Calvo, Jan Pravsgaard Christensen, and Linda van Oosten
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0301 basic medicine ,viruses ,Laboratory of Virology ,General Physics and Astronomy ,Antibodies, Viral ,law.invention ,Mice ,0302 clinical medicine ,Immunogenicity, Vaccine ,law ,Mice, Inbred BALB C ,Multidisciplinary ,biology ,Molecular medicine ,Chemistry ,Immunogenicity ,Antibody titer ,PE&RC ,Recombinant Proteins ,3. Good health ,Vaccination ,Titer ,Capsid ,Spike Glycoprotein, Coronavirus ,Recombinant DNA ,Female ,Angiotensin-Converting Enzyme 2 ,Antibody ,Protein Binding ,COVID-19 Vaccines ,Science ,Article ,General Biochemistry, Genetics and Molecular Biology ,Laboratorium voor Virologie ,03 medical and health sciences ,Antigen ,Animals ,Humans ,Life Science ,Serologic Tests ,SARS-CoV-2 ,COVID-19 ,General Chemistry ,biochemical phenomena, metabolism, and nutrition ,Virology ,Antibodies, Neutralizing ,Kinetics ,030104 developmental biology ,Preclinical research ,biology.protein ,030217 neurology & neurosurgery - Abstract
The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP vaccine is a highly promising candidate for preventing COVID-19., Here the authors generate a capsid-like particle based vaccine candidate displaying the receptor-binding domain of the SARS-CoV-2 spike protein and show induction of neutralizing antibodies after intramuscular prime-boost immunization in mice.
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