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

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 th...

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Autores principales: Jansen van Vuren, Petrus, McAuley, Alexander J., Kuiper, Michael J., Singanallur, Nagendrakumar Balasubramanian, Bruce, Matthew P., Riddell, Shane, Goldie, Sarah, Mangalaganesh, Shruthi, Chahal, Simran, Drew, Trevor W., Blasdell, Kim R., Tachedjian, Mary, Caly, Leon, Druce, Julian D., Ahmed, Shahbaz, Khan, Mohammad Suhail, Malladi, Sameer Kumar, Singh, Randhir, Pandey, Suman, Varadarajan, Raghavan, Vasan, Seshadri S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031315/
https://www.ncbi.nlm.nih.gov/pubmed/35458530
http://dx.doi.org/10.3390/v14040800
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author Jansen van Vuren, Petrus
McAuley, Alexander J.
Kuiper, Michael J.
Singanallur, Nagendrakumar Balasubramanian
Bruce, Matthew P.
Riddell, Shane
Goldie, Sarah
Mangalaganesh, Shruthi
Chahal, Simran
Drew, Trevor W.
Blasdell, Kim R.
Tachedjian, Mary
Caly, Leon
Druce, Julian D.
Ahmed, Shahbaz
Khan, Mohammad Suhail
Malladi, Sameer Kumar
Singh, Randhir
Pandey, Suman
Varadarajan, Raghavan
Vasan, Seshadri S.
author_facet Jansen van Vuren, Petrus
McAuley, Alexander J.
Kuiper, Michael J.
Singanallur, Nagendrakumar Balasubramanian
Bruce, Matthew P.
Riddell, Shane
Goldie, Sarah
Mangalaganesh, Shruthi
Chahal, Simran
Drew, Trevor W.
Blasdell, Kim R.
Tachedjian, Mary
Caly, Leon
Druce, Julian D.
Ahmed, Shahbaz
Khan, Mohammad Suhail
Malladi, Sameer Kumar
Singh, Randhir
Pandey, Suman
Varadarajan, Raghavan
Vasan, Seshadri S.
author_sort Jansen van Vuren, Petrus
collection PubMed
description 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.
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spelling pubmed-90313152022-04-23 Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice Jansen van Vuren, Petrus McAuley, Alexander J. Kuiper, Michael J. Singanallur, Nagendrakumar Balasubramanian Bruce, Matthew P. Riddell, Shane Goldie, Sarah Mangalaganesh, Shruthi Chahal, Simran Drew, Trevor W. Blasdell, Kim R. Tachedjian, Mary Caly, Leon Druce, Julian D. Ahmed, Shahbaz Khan, Mohammad Suhail Malladi, Sameer Kumar Singh, Randhir Pandey, Suman Varadarajan, Raghavan Vasan, Seshadri S. Viruses Article 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. MDPI 2022-04-13 /pmc/articles/PMC9031315/ /pubmed/35458530 http://dx.doi.org/10.3390/v14040800 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jansen van Vuren, Petrus
McAuley, Alexander J.
Kuiper, Michael J.
Singanallur, Nagendrakumar Balasubramanian
Bruce, Matthew P.
Riddell, Shane
Goldie, Sarah
Mangalaganesh, Shruthi
Chahal, Simran
Drew, Trevor W.
Blasdell, Kim R.
Tachedjian, Mary
Caly, Leon
Druce, Julian D.
Ahmed, Shahbaz
Khan, Mohammad Suhail
Malladi, Sameer Kumar
Singh, Randhir
Pandey, Suman
Varadarajan, Raghavan
Vasan, Seshadri S.
Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice
title Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice
title_full Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice
title_fullStr Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice
title_full_unstemmed Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice
title_short Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice
title_sort highly thermotolerant sars-cov-2 vaccine elicits neutralising antibodies against delta and omicron in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031315/
https://www.ncbi.nlm.nih.gov/pubmed/35458530
http://dx.doi.org/10.3390/v14040800
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