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

Autor: Khan MS; Molecular Biophysics Unit (MBU), Indian Institute of Science, Bengaluru 560012, India., Jakob V; Vaccine Formulation Institute, Rue du Champ-Blanchot 4, 1228 Plan-les-Ouates, Switzerland., Singh R; Mynvax Private Limited, 3rd Floor, Brigade MLR Centre, No. 50, Vani Vilas Road, Basavanagudi, Bengaluru 560004, India., Rajmani RS; Molecular Biophysics Unit (MBU), Indian Institute of Science, Bengaluru 560012, India., Kumar S; Virology Unit, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Chandigarh 160036, India., Lemoine C; Vaccine Formulation Institute, Rue du Champ-Blanchot 4, 1228 Plan-les-Ouates, Switzerland., Kleanthous H; Bill and Melinda Gates Foundation, Seattle, WA 98109, USA., Ringe RP; Virology Unit, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Chandigarh 160036, India., Dubois PM; Vaccine Formulation Institute, Rue du Champ-Blanchot 4, 1228 Plan-les-Ouates, Switzerland., Varadarajan R; Molecular Biophysics Unit (MBU), Indian Institute of Science, Bengaluru 560012, India.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2023 Dec 12; Vol. 15 (12). Date of Electronic Publication: 2023 Dec 12.
DOI: 10.3390/pharmaceutics15122759
Abstrakt: 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.
Databáze: MEDLINE
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