Abstract

With the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly reactive immune responses that could improve protection. However, the contribution of the S2 subunit in improving the overall efficacy of vaccines remains unclear. Therefore, we designed, and evaluated the immunogenicity and protective potential of a stabilized SARS-CoV-2 Receptor Binding Domain (RBD) fused to a stabilized S2. Immunogens were expressed as soluble proteins with approximately fivefold higher purified yield than the Spike ectodomain and formulated along with Squalene-in-water emulsion (SWE) adjuvant. Immunization with S2 alone failed to elicit a neutralizing immune response, but significantly reduced lung viral titers in mice challenged with the heterologous Beta variant. In hamsters, SWE-formulated RS2 (a genetic fusion of stabilized RBD with S2) showed enhanced immunogenicity and efficacy relative to corresponding RBD and Spike formulations. Despite being based on the ancestral Wuhan strain of SARS-CoV-2, RS2 elicited broad neutralization, including against Omicron variants (BA.1, BA.5 and BF.7), and the clade 1a WIV-1 and SARS-CoV-1 strains. RS2 elicited sera showed enhanced competition with both S2 directed and RBD Class 4 directed broadly neutralizing antibodies, relative to RBD and Spike elicited sera. When lyophilized, RS2 retained antigenicity and immunogenicity even after incubation at 37 °C for a month. The data collectively suggest that the RS2 immunogen is a promising modality to combat SARS-CoV-2 variants.

Details

Title
Enhanced protective efficacy of a thermostable RBD-S2 vaccine formulation against SARS-CoV-2 and its variants
Author
Mittal, Nidhi 1 ; Kumar, Sahil 2 ; Rajmani, Raju S. 1 ; Singh, Randhir 3   VIAFID ORCID Logo  ; Lemoine, Céline 4 ; Jakob, Virginie 4 ; BJ, Sowrabha 3 ; Jagannath, Nayana 3   VIAFID ORCID Logo  ; Bhat, Madhuraj 3 ; Chakraborty, Debajyoti 1   VIAFID ORCID Logo  ; Pandey, Suman 3 ; Jory, Aurélie 5 ; SA, Suba Soundarya 5   VIAFID ORCID Logo  ; Kleanthous, Harry 6   VIAFID ORCID Logo  ; Dubois, Patrice 7 ; Ringe, Rajesh P. 2 ; Varadarajan, Raghavan 1 

 Molecular Biophysics Unit (MBU), Indian Institute of Science, Bengaluru, India (GRID:grid.464869.1) (ISNI:0000 0000 9288 3664) 
 Virology Unit, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Chandigarh, India (GRID:grid.417641.1) (ISNI:0000 0004 0504 3165) 
 Mynvax Private Limited; 3rd Floor, Brigade MLR Centre, No.50, Vani Vilas Road, Basavanagudi, Bengaluru, India (GRID:grid.464869.1) 
 Vaccine Formulation Institute; Rue du Champ-Blanchod 4, Plan-les-Ouates, Switzerland (GRID:grid.464869.1) 
 National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, India (GRID:grid.510243.1) (ISNI:0000 0004 0501 1024) 
 Bill and Melinda Gates Foundation, Seattle, USA (GRID:grid.418309.7) (ISNI:0000 0000 8990 8592) 
 Vaccine Formulation Institute; Rue du Champ-Blanchod 4, Plan-les-Ouates, Switzerland (GRID:grid.418309.7) 
Pages
161
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20590105
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2881548352
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.