Aqueous vaccine formulations are highly susceptible to degradation at elevated temperatures, necessitating cold storage throughout their lifecycle, which increases overall costs. Additionally, most vaccines are administered via the parenteral route, requiring trained professionals and often leading to pain and distress, thereby reducing patient compliance. A major challenge in vaccine development is the in vivo evaluation of candidates during the screening stage, a process that is labor-intensive, costly, and time-consuming, with variable reproducibility. This study aims to develop a nanoparticulate vaccine formulation while concurrently establishing a dendritic cell-based model for efficient vaccine screening in vitro. Fluorescence imaging and staining assays were employed to assess the uptake of vaccine-loaded nanoparticles in HeLa and dendritic cells. Cell Mask Orange assay confirmed intracellular localization of the nanoparticles. Enzyme-linked immunosorbent assay (ELISA) was performed to quantify cytokine (IL-6, TNF-α, and IL-1β) secretion by dendritic cells following stimulation with the nanoparticulate vaccine. Statistical analysis revealed significant cytokine release, indicating successful immune activation. These findings suggest that vaccines can be successfully encapsulated into nanoparticulate formulations and that dendritic cells provide a promising in vitro model for high-throughput vaccine screening. Additionally, this study paves the way for further investigation into optimizing nanoparticle formulations and in vitro screening methodologies to enhance vaccine development efficiency. This study highlights the importance of in vitro dendritic cell models as predictive tools for vaccine screening, reducing reliance on animal testing while accelerating vaccine development timelines.