Record Details

A Stabilized, Monomeric, Receptor Binding Domain Elicits High-Titer Neutralizing Antibodies Against All SARS-CoV-2 Variants of Concern

DIR@IMTECH: CSIR-Institute of Microbial Technology

View Archive Info
 
 
Field Value
 
Title A Stabilized, Monomeric, Receptor Binding Domain Elicits High-Titer Neutralizing Antibodies Against All SARS-CoV-2 Variants of Concern
 
Creator Ahmed, S
Khan, Mohd S
Gayathri, Savitha
Singh, Randhir
Kumar, Sahil
Patel, U R
Malladi, Sameer Kumar
Rajmani, Raju S
Vuren, P J
Riddell, Shane
Girish, Nidhi
Reddy, P
Upadhyay, A
Ringe, Rajesh P.
Raghavan, V
 
Subject QR Microbiology
 
Description Saturation suppressor mutagenesis was used to generate thermostable mutants of the SARS-CoV-2 spike receptor-binding domain (RBD). A triple mutant with an increase in thermal melting temperature of ~7°C with respect to the wild-type B.1 RBD and was expressed in high yield in both mammalian cells and the microbial host, Pichia pastoris, was downselected for immunogenicity studies. An additional derivative with three additional mutations from the B.1.351 (beta) isolate was also introduced into this background. Lyophilized proteins were resistant to high-temperature exposure and could be stored for over a month at 37°C. In mice and hamsters, squalene-in-water emulsion (SWE) adjuvanted formulations of the B.1-stabilized RBD were considerably more immunogenic than RBD lacking the stabilizing mutations and elicited antibodies that neutralized all four current variants of concern with similar neutralization titers. However, sera from mice immunized with the stabilized B.1.351 derivative showed significantly decreased neutralization titers exclusively against the B.1.617.2 (delta) VOC. A cocktail comprising stabilized B.1 and B.1.351 RBDs elicited antibodies with qualitatively improved neutralization titers and breadth relative to those immunized solely with either immunogen. Immunized hamsters were protected from high-dose viral challenge. Such vaccine formulations can be rapidly and cheaply produced, lack extraneous tags or additional components, and can be stored at room temperature. They are a useful modality to combat COVID-19, especially in remote and low-resource settings.
 
Publisher Frontiers
 
Date 2021-12-09
 
Type Article
PeerReviewed
 
Relation https://www.frontiersin.org/articles/10.3389/fimmu.2021.765211/full#h12
http://crdd.osdd.net/open/2945/
 
Identifier Ahmed, S and Khan, Mohd S and Gayathri, Savitha and Singh, Randhir and Kumar, Sahil and Patel, U R and Malladi, Sameer Kumar and Rajmani, Raju S and Vuren, P J and Riddell, Shane and Girish, Nidhi and Reddy, P and Upadhyay, A and Ringe, Rajesh P. and Raghavan, V (2021) A Stabilized, Monomeric, Receptor Binding Domain Elicits High-Titer Neutralizing Antibodies Against All SARS-CoV-2 Variants of Concern. Frontiers in immunology. ISSN 1664-3224