Graduate Researcher University of California, Irvine Irvine, California, United States
Disclosure(s):
Caecilia Sasikirana Basirin: No financial relationships to disclose
Introduction/Rationale: Nanoparticle delivery systems are widely used to improve vaccine adjuvant effects. IVAX, a nanoparticulate adjuvant system encapsulating a combination of Toll-like receptor (TLR) 4 and TLR9 agonists, has shown significant promise in various vaccine models. However, the role of nanoparticles in the adjuvant system was not well-defined. This study aims to investigate how different nanoparticle carriers affect the immunogenic performance of adjuvanted vaccine formulations in a melanoma vaccine model.
Methods: Three representative nanoparticles, including nanoemulsion (IVAX-1), cationic lipid nanoparticle (LNP; IVAX-5), and ionizable LNP (IVAX-6), were formulated to encapsulate a combination adjuvant of CpG and MPLA using ovalbumin (OVA) as a model antigen. Physicochemical properties of all three nanoparticles were characterized, followed by the evaluation of NF-κB activation using the RAW-Blue reporter assay. Furthermore, humoral and cellular immune responses, reactogenicity, and antitumor efficacy across vaccine formulations were evaluated in B16F10-OVA melanoma models.
Results: Nanoparticle-formulated TLR agonist adjuvants enhanced NF-κB activation compared to controls, indicating a nanoparticle-dependent effect on innate immune signaling. Mice immunized with adjuvanted vaccines showed complete tumor protection through the study endpoint, whereas buffer-treated and antigen-only control groups developed progressive tumor growth. Immunoprofiling post-vaccination revealed the differences in immune responses induced by different nanoparticle formulations.
Conclusion: Together, this study highlights the importance of nanoparticle carrier design in shaping the performance of TLR-agonist adjuvanted cancer vaccines.