ArticleDrug delivery and translational research2026
Encapsulation of the lipidated TLR7/8 agonist INI-4001 into ionic liposomes impacts H7 influenza antigen-specific immune responses.
Article in Drug delivery and translational research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Toll-like receptors (TLRs) are the best characterized family of Pattern Recognition Receptor-targeting adjuvants. Activation of TLR7/8 in particular, enhances antigen presentation by dendritic cells and macrophages, boosting Th1-mediated adaptive immune responses. However, poor pharmacokinetics and systemic toxicity of some TLR7/8 ligands hinder their clinical translation. Lipidation and incorporation of TLR7/8 ligands into liposomes can reduce systemic exposure, improve pharmacokinetics, pharmacodynamics, and presentation to immune cells. In the present study, a series of liposomal formulations incorporating a novel lipidated TLR7/8 agonist, INI-4001, were prepared to evaluate the effect of surface charge and lipid composition on the colloidal stability, cytotoxicity, innate immune activation, and adjuvant activity when combined with the recombinant Influenza A/Shanghai/1/13 (H7N9) Virus Hemagglutinin antigen (H7). The tested formulations include neutral (DOPC/Cholesterol), anionic (DOPG/Cholesterol), and cationic (DOPC/DC-Cholesterol, DOPC/GL67, DOEPC/Cholesterol, DOTAP/Cholesterol, or DOTAP + DDAB/Cholesterol) liposomes. These studies demonstrated that alongside the type and magnitude of particle surface charge, lipid composition was a determining factor in the regulation of immunogenicity and biocompatibility of INI-4001-loaded liposomes. Among the cationic liposomes evaluated, DOPC/DC-Cholesterol liposomes exhibited the lowest in vitro cytotoxicity while enhancing TNF-α induction from human peripheral blood mononuclear cells. Furthermore, murine immunization studies demonstrated that the same formulation enhanced H7-specific IgG titers and induced a Th1-polarized cell-mediated response compared to H7 antigen alone or the matched liposome lacking INI-4001. Of note, the anionic DOPG/Cholesterol INI-4001 liposomes induced a rapid response with significantly higher IgG titers after a single immunization and promoted strong Th1-polarized cellular responses, which may be advantageous in an influenza pandemic setting. These findings highlight the key role of liposome characteristics in optimizing the safety and immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines.
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