Jansen van Vuren, P and McAuley, AJ and Kuiper, MJ and Singanallur, NB and Bruce, MP and Riddell, S and Goldie, S and Mangalaganesh, S and Chahal, S and Drew, TW and Blasdell, KR and Tachedjian, M and Caly, L and Druce, JD and Ahmed, S and Khan, MS and Malladi, SK and Singh, R and Pandey, S and Varadarajan, R and Vasan, SS (2022) Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice. In: Viruses, 14 (4).
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Abstract
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.
| Item Type: | Journal Article |
|---|---|
| Publication: | Viruses |
| Publisher: | MDPI |
| Additional Information: | The copyright for this article belongs to Authors. |
| Keywords: | coronavirus spike glycoprotein; neutralizing antibody; spike protein, SARS-CoV-2; virus antibody, animal; genetics; human; mouse; prevention and control, Animals; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Humans; Mice; SARS-CoV-2; Spike Glycoprotein, Coronavirus |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 19 May 2022 04:33 |
| Last Modified: | 19 May 2022 04:33 |
| URI: | https://eprints.iisc.ac.in/id/eprint/72038 |
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