Protein-based vaccines rely on adjuvants for effectiveness, but many are proprietary. The Vaccine Formulation Institute (VFI) is developing open-access, potent adjuvants for global clinical use.

We tested four VFI adjuvants (liposome-based LQ, LMQ; squalene emulsion-based SQ, SMQ, all with immunostimulators) with the R21 malaria vaccine in a mouse model. While all four elicited strong antibody responses, LMQ and SQ provided the highest degree of protection (80-100%) against malaria.

Interestingly, LMQ and SQ activated the innate immune system differently. Only LMQ activated the NLRP3 inflammasome, leading to a Th1-type adaptive immune response, while SQ drove a Th2-type response. This study highlights how formulation changes influence immune responses, demonstrating that different immune mechanisms can achieve comparable protective efficacy.