Emulsion and liposome-based adjuvanted R21 vaccine formulations mediate protection against malaria through distinct immune mechanisms (2023, Cell Reports Medicine)

Protein-based vaccines with added immunostimulators (adjuvants) are highly effective, but many of the most successful adjuvants are proprietary and unavailable to vaccine developers. The Vaccine Formulation Institute (VFI) in Switzerland are developing safe and potent adjuvants that will be available for clinical use globally, on an open-acess basis.
In this study, we examined four VFI adjuvants, testing their efficacy with the R21 malaria vaccine in a mouse model of malaria. The adjuvants comprised either liposomes (LQ, LMQ) or squalene emulsion (SQ, SMQ) with added immunostimulators (TLR4 agonist and QS21 saponin).
All four adjuvants generated equally potent antibody responses but resulted in different levels of protection against malaria, with LMQ and SQ offering 80-100% protection. The two adjuvants were found to activate the innate immune system through different pathways: only LMQ was found to activate the NLRP3 inflammasome, a protein complex involved in innate immune responses. This early difference in immune signalling led to a different type of adaptive immune response, with LMQ driving a predominantly Th1-type and SQ Th2-type response.
This study demonstrates how modifying the vaccine formulation results in a different type of immune response while illustrating how different immune mechanisms can drive equally high protective efficacy.