2. Academic Validation
  3. Emulsion and liposome-based adjuvanted R21 vaccine formulations mediate protection against malaria through distinct immune mechanisms

Emulsion and liposome-based adjuvanted R21 vaccine formulations mediate protection against malaria through distinct immune mechanisms

  • Cell Rep Med. 2023 Nov 21;4(11):101245. doi: 10.1016/j.xcrm.2023.101245.
Sören Reinke 1,  Eirini Pantazi 2,  Gabrielle R Chappell 2,  Alexandra Sanchez-Martinez 1,  Romain Guyon 1,  Joannah R Fergusson 1,  Ahmed M Salman 1,  Anjum Aktar 2,  Ekta Mukhopadhyay 1,  Roland A Ventura 3,  Floriane Auderset 3,  Patrice M Dubois 3,  Nicolas Collin 3,  Adrian V S Hill 1,  Jelena S Bezbradica 4,  Anita Milicic 5
Affiliations

Affiliations

  • 1 The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK.
  • 2 Kennedy Institute of Rheumatology Research, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Medical Sciences Division, University of Oxford, Oxford OX3 7FY, UK.
  • 3 Vaccine Formulation Institute, Rue du Champ-Blanchod 4, 1228 Plan-Les-Ouates, Switzerland.
  • 4 Kennedy Institute of Rheumatology Research, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Medical Sciences Division, University of Oxford, Oxford OX3 7FY, UK. Electronic address: jelena.bezbradica@kennedy.ox.ac.uk.
  • 5 The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: anita.milicic@ndm.ox.ac.uk.
PMID: 37913775 DOI: 10.1016/j.xcrm.2023.101245
Abstract

Adjuvanted protein vaccines offer high efficacy, yet most potent adjuvants remain proprietary. Several Adjuvant compounds are being developed by the Vaccine Formulation Institute in Switzerland for global open access clinical use. In the context of the R21 malaria vaccine, in a mouse challenge model, we characterize the efficacy and mechanism of action of four Vaccine Formulation Institute adjuvants: two liposomal (LQ and LMQ) and two squalene emulsion-based adjuvants (SQ and SMQ), containing QS-21 saponin (Q) and optionally a synthetic TLR4 Agonist (M). Two R21 vaccine formulations, R21/LMQ and R21/SQ, offer the highest protection (81%-100%), yet they trigger different innate sensing mechanisms in macrophages with LMQ, but not SQ, activating the NLRP3 inflammasome. The resulting in vivo adaptive responses have a different TH1/TH2 balance and engage divergent innate pathways while retaining high protective efficacy. We describe how modular changes in vaccine formulation allow for the dissection of the underlying immune pathways, enabling future mechanistically informed vaccine design.

Keywords

NLRP3; QS-21; TLR4; adjuvants; emulsions; inflammasome; liposomes; malaria; saponin; vaccines.

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