Khan, MS and Jakob, V and Singh, R and Rajmani, RS and Kumar, S and Lemoine, C and Kleanthous, H and Ringe, RP and Dubois, PM and Varadarajan, R (2023) Enhancing Immunogenicity of a Thermostable, Efficacious SARS-CoV-2 Vaccine Formulation through Oligomerization and Adjuvant Choice. In: Pharmaceutics, 15 (12).
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Abstract
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. © 2023 by the authors.
| Item Type: | Journal Article |
|---|---|
| Publication: | Pharmaceutics |
| Publisher: | Multidisciplinary Digital Publishing Institute (MDPI) |
| Additional Information: | The copyright for this article belongs to Author. |
| Keywords: | adjuvant; aluminum hydroxide; gamma interferon; interleukin 13; interleukin 2; interleukin 4; interleukin 5; ketamine; penicillin derivative; saponin; SARS-CoV-2 vaccine; squalene; streptomycin; toll like receptor 4; xylazine, animal experiment; antibody titer; Article; B lymphocyte; controlled study; drug formulation; emulsion; enzyme linked immunosorbent assay; female; genetic transfection; human; immobilized metal affinity chromatography; mouse; nonhuman; oligomerization; protein expression; protein purification; receptor binding; size exclusion chromatography; solubilization; T lymphocyte; temperature; thermostability; trimerization; vaccination; vaccine immunogenicity; virus load |
| Department/Centre: | Others |
| Date Deposited: | 01 Mar 2024 09:58 |
| Last Modified: | 01 Mar 2024 09:58 |
| URI: | https://eprints.iisc.ac.in/id/eprint/84026 |
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