Record Details

Enhancing Immunogenicity of a Thermostable, Efficacious SARS-CoV-2 Vaccine Formulation through Oligomerization and Adjuvant Choice

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Enhancing Immunogenicity of a Thermostable, Efficacious SARS-CoV-2 Vaccine Formulation through Oligomerization and Adjuvant Choice
 
Creator Khan, Mohammad Suhail
Jakob, Virginie
Singh, Randhir
Rajmani, Raju S
Kumar, Sahil
Lemonie , Celine
Kleanthous , Harry
Ringe, Rajesh P.
Dubois , Patrice M
Varadarajan, Raghavan
 
Subject QR Microbiology
 
Description Currently deployed SARS-CoV-2 vaccines all require storage at refrigerated or sub-zero temperatures. We demonstrate that after month-long incubation at 37 °C, solubilization, and formulation with squalene-in-water emulsion adjuvant, a stabilized receptor binding domain retains immunogenicity and protective efficacy. We also examine the effects of trimerization of the stabilized RBD, as well as of additional adjuvants, on both B and T-cell responses. The additional emulsion or liposome-based adjuvants contained a synthetic TLR-4 ligand and/or the saponin QS-21. Trimerization enhanced immunogenicity, with significant antibody titers detectable after a single immunization. Saponin-containing adjuvants elicited enhanced immunogenicity relative to both emulsion and aluminum hydroxide adjuvanted formulations lacking these immunostimulants. Trimeric RBD formulated with liposomal based adjuvant containing both TLR-4 ligand and saponin elicited a strongly Th1 biased response, with ~10-fold higher neutralization titers than the corresponding aluminum hydroxide adjuvanted formulation. The SARS-CoV-2 virus is now endemic in humans, and it is likely that periodic updating of vaccine formulations in response to viral evolution will continue to be required to protect vulnerable individuals. In this context, it is desirable to have efficacious, thermostable vaccine formulations to facilitate widespread vaccine coverage, including in low- and middle-income countries, where global access rights to clinically de-risked adjuvants will be important moving forward.
 
Publisher MDPI
 
Date 2023-12
 
Type Article
PeerReviewed
 
Relation https://www.mdpi.com/1999-4923/15/12/2759
http://crdd.osdd.net/open/3184/
 
Identifier Khan, Mohammad Suhail and Jakob, Virginie and Singh, Randhir and Rajmani, Raju S and Kumar, Sahil and Lemonie , Celine and Kleanthous , Harry and Ringe, Rajesh P. and Dubois , Patrice M and Varadarajan, Raghavan (2023) Enhancing Immunogenicity of a Thermostable, Efficacious SARS-CoV-2 Vaccine Formulation through Oligomerization and Adjuvant Choice. Pharmaceutics, 15 (12).