Wei, L., et al. Saponin derivative and MPLA-adjuvanted intranasal protein nanoparticle vaccines induce potent mucosal immunity and durable heterologous influenza protection in mice
Nanomedicine, 2026 Aug 19:103008. PMID: 42617671
The authors introduce a novel intranasal protein nanoparticle influenza vaccine formulated with a semisynthetic saponin derivative, VSA-2, combined with MPLA, demonstrating potent and durable mucosal immunity and heterologous protection in mice. The plant-derived saponin derivative serves as an adjuvant that, when combined with MPLA, synergistically enhances immune activation.
The intranasal vaccine formulation adjuvanted with MPLA and the semisynthetic saponin VSA-2 (PMV) elicited strong systemic and mucosal immune responses, including high titers of cross-reactive IgG, IgA, and tissue-resident memory T cells, indicating robust immunogenicity. The vaccine effectively promoted innate immune activation, early recruitment of innate immune cells, and durable immune responses lasting at least six months, with persistent antibody titers and functional T cells. Importantly, the vaccine provided complete protection against heterologous influenza challenges, with minimal pathology observed in lung tissues, suggesting a favorable safety profile.
This work is especially compelling for those interested in saponin adjuvants because it showcases how rational design of saponin derivatives (like VSA-2) can significantly improve mucosal vaccine efficacy and durability, addressing longstanding challenges in mucosal immunization such as short-lived immunity and limited cross-protection, thus advancing the development of safer, more effective adjuvanted vaccines for respiratory pathogens.
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