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Article

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

1
Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia
2
Data61, Commonwealth Scientific and Industrial Research Organisation, Docklands, VIC 3008, Australia
3
Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia
4
Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital and The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
5
Molecular Biophysics Unit, Indian Institute of Science, Bengaluru 560012, India
6
Mynvax Private Limited, ES-12, Incubation Centre, Society for Innovation and Development, Indian Institute of Science, Bengaluru 560012, India
7
Department of Health Sciences, University of York, York YO10 5DD, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Dapeng Li, Ahmed O. Hassan and Jingyou Yu
Viruses 2022, 14(4), 800; https://doi.org/10.3390/v14040800
Received: 8 March 2022 / Revised: 6 April 2022 / Accepted: 9 April 2022 / Published: 13 April 2022
(This article belongs to the Special Issue Vaccines for Emerging Zoonotic Viruses)
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. View Full-Text
Keywords: AlphaFold; biomolecular modelling; COVID-19; Omicron; receptor-binding domain (RBD); SARS-CoV-2; thermotolerant vaccine; vaccine equity; vaccine matching; variants of concern (VOC) AlphaFold; biomolecular modelling; COVID-19; Omicron; receptor-binding domain (RBD); SARS-CoV-2; thermotolerant vaccine; vaccine equity; vaccine matching; variants of concern (VOC)
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MDPI and ACS Style

Jansen van Vuren, P.; McAuley, A.J.; Kuiper, M.J.; Singanallur, N.B.; Bruce, M.P.; Riddell, S.; Goldie, S.; Mangalaganesh, S.; Chahal, S.; Drew, T.W.; Blasdell, K.R.; Tachedjian, M.; Caly, L.; Druce, J.D.; Ahmed, S.; Khan, M.S.; Malladi, S.K.; Singh, R.; Pandey, S.; Varadarajan, R.; Vasan, S.S. Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice. Viruses 2022, 14, 800. https://doi.org/10.3390/v14040800

AMA Style

Jansen van Vuren P, McAuley AJ, Kuiper MJ, Singanallur NB, Bruce MP, Riddell S, Goldie S, Mangalaganesh S, Chahal S, Drew TW, Blasdell KR, Tachedjian M, Caly L, Druce JD, Ahmed S, Khan MS, Malladi SK, Singh R, Pandey S, Varadarajan R, Vasan SS. Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice. Viruses. 2022; 14(4):800. https://doi.org/10.3390/v14040800

Chicago/Turabian Style

Jansen van Vuren, Petrus, Alexander J. McAuley, Michael J. Kuiper, Nagendrakumar Balasubramanian Singanallur, Matthew P. Bruce, Shane Riddell, Sarah Goldie, Shruthi Mangalaganesh, Simran Chahal, Trevor W. Drew, Kim R. Blasdell, Mary Tachedjian, Leon Caly, Julian D. Druce, Shahbaz Ahmed, Mohammad Suhail Khan, Sameer Kumar Malladi, Randhir Singh, Suman Pandey, Raghavan Varadarajan, and Seshadri S. Vasan. 2022. "Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice" Viruses 14, no. 4: 800. https://doi.org/10.3390/v14040800

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