Postdoctoral scholar Lawrence Berkeley National Lab, California, United States
Disclosure(s):
Priyanka Talukdar, PhD: No financial relationships to disclose
Introduction/Rationale: QS-21, a saponin-based adjuvant, is a key component of several licensed vaccines and is commonly co-formulated with monophosphoryl lipid A (MPLA) to enhance adaptive immune responses. Although its adjuvant efficacy is well established, the broader potential of QS-21 in combination with other pattern recognition receptor (PRR) agonists remains insufficiently characterized. In this work, we systematically investigated the immunomodulatory properties of QS-21 paired with five different PRR agonists: MPLA (TLR4 agonist), L18-MDP (NOD2 agonist), R848 (TLR7/8 agonist), CpG ODN (TLR9 agonist), and Poly I:C (TLR3 agonist).
Methods: Cytotoxicity assays were first conducted to define the lowest concentrations of QS-21 and each agonist, that were non-toxic yet capable of stimulating cells. Differentiated THP-1 macrophages were subsequently treated with individual agonists, QS-21 combinations, or MPLA combinations, and activation was assessed through surface activation marker expression and cytokine/chemokine secretion profiles. To further delineate the molecular mechanisms underlying these responses, we performed RNA sequencing and metabolomics profiling to identify distinct immunological signatures associated with each treatment.
Results: Our findings reveal that, although the PRR agonists exhibited variable activation capacities, the combinations of QS-21+MPLA with either Poly I:C or L18-MDP produced the strongest macrophage activation, surpassing the effects of single agents.
Conclusion: Collectively, these results expand the understanding of QS-21’s synergistic potential with diverse PRR agonists and suggest new avenues for adjuvant design. Notably, Poly I:C emerges as a particularly promising co-adjuvant with QS-21, capable of engaging complementary innate immune pathways to enhance vaccine-induced immunity.
