Li, Q., et al. Quillaja saponaria fraction QS-18 as an adjuvant for liposomal seasonal influenza vaccines. NPJ Vaccines, 2026 Apr 28, PMID: 42049779
This study presents a pioneering evaluation of QS-18, an abundant fraction from
Quillaja saponaria, as a vaccine adjuvant within liposomal formulations for seasonal
influenza. Traditionally, QS-21 has been the favored saponin due to its potent
immunostimulatory properties and established clinical use, but its limited supply and
potential toxicity have hindered broader application. QS-18, despite its higher
abundance, has been largely avoided due to concerns over toxicity. This research
demonstrates that when incorporated into liposomes with cholesterol, QS-18 exhibits
significantly reduced hemolytic activity and toxicity, yet maintains comparable
immunogenicity and protective efficacy to QS-21 in mice and ferrets. The work is
unique because it offers a potential pathway to leverage an abundant, cost-effective, and effective plant-derived saponin, addressing supply bottlenecks and safety
concerns, and paving the way for more scalable and accessible adjuvant
formulations in vaccine development. Its significance lies in repurposing a previously
overlooked fraction, highlighting the importance of formulation strategies in unlocking
its clinical potential.
QS-18, when formulated within cholesterol-containing liposomes, exhibits markedly
reduced hemolytic activity and toxicity compared to its free form, while retaining
robust adjuvant properties. Immunization with QS-18 adjuvanted liposomes elicited
high titers of functional, neutralizing antibodies against multiple influenza strains in
mice and ferrets, comparable to QS-21-based formulations. Furthermore, both QS-
18 and QS-21 liposomal vaccines conferred complete protection against lethal
influenza challenge in mice and reduced early viral loads in ferrets. Safety
assessments indicated that liposomal QS-18 was well tolerated in mice and rabbits,
with only transient mild reactogenicity, supporting its potential as a safe and effective
adjuvant.
Overall, the results demonstrate that QS-18 can serve as a viable, scalable
alternative to QS-21 in liposomal vaccine formulations without compromising efficacy
or safety. The next steps, as extrapolated by the authors, are to conduct more
detailed toxicity and safety evaluations, including mechanistic studies of membrane
interactions and downstream inflammatory responses, to optimize doses and
formulations for better safety-efficacy balance, and to pursue clinical trials to assess
the immunogenicity, safety, and tolerability of QS-18-containing vaccines in humans.
Comments from DK. While the current results are promising, the limited scope of
safety assessments underscores the need for more comprehensive toxicity and
mechanistic studies to fully elucidate the safety profile of QS-18, particularly
concerning membrane interactions and inflammatory responses. Given the
differences between animal models and humans in immune responses and
reactogenicity, careful translation and further studies are necessary. Ensuring
appropriate purity and consistency is essential for accurate evaluation of its safety
and efficacy profiles. Fortunately, DK offers QS-18 at various purity levels
suitable for both research and clinical development.
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