Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice.

Autor:	Jansen van Vuren P; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia., McAuley AJ; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia., Kuiper MJ; Data61, Commonwealth Scientific and Industrial Research Organisation, Docklands, VIC 3008, Australia., Singanallur NB; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia., Bruce MP; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia., Riddell S; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia., Goldie S; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia., Mangalaganesh S; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia.; Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia., Chahal S; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia., Drew TW; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia., Blasdell KR; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia., Tachedjian M; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia., Caly L; Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital and The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia., Druce JD; Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital and The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia., Ahmed S; Molecular Biophysics Unit, Indian Institute of Science, Bengaluru 560012, India., Khan MS; Molecular Biophysics Unit, Indian Institute of Science, Bengaluru 560012, India., Malladi SK; Molecular Biophysics Unit, Indian Institute of Science, Bengaluru 560012, India., Singh R; Mynvax Private Limited, ES-12, Incubation Centre, Society for Innovation and Development, Indian Institute of Science, Bengaluru 560012, India., Pandey S; Mynvax Private Limited, ES-12, Incubation Centre, Society for Innovation and Development, Indian Institute of Science, Bengaluru 560012, India., Varadarajan R; Molecular Biophysics Unit, Indian Institute of Science, Bengaluru 560012, India., Vasan SS; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia.; Department of Health Sciences, University of York, York YO10 5DD, UK.
Jazyk:	angličtina
Zdroj:	Viruses [Viruses] 2022 Apr 13; Vol. 14 (4). Date of Electronic Publication: 2022 Apr 13.
DOI:	10.3390/v14040800
Abstrakt:	As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We previously developed highly thermo-tolerant monomeric and trimeric receptor-binding domain derivatives that can withstand 100 °C for 90 min and 37 °C for four weeks and help eliminate cold-chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations and a 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for upcoming Phase I human clinical trials and that there is potential for increasing the efficacy with vaccine matching to improve the responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions, which show that, while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain.
Databáze:	MEDLINE
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