Abstract
Conventional DNA vaccine strategies usually employ a regimen of immunizations at 2-week or longer intervals to induce effective memory cell-dependent immune responses. Clinical cancer treatment requires a faster immunization strategy to contend with tumor progression. In this study, a novel fast immunization strategy was established, wherein a DNA vaccine was intramuscularly administered on days 0, 2, and 5 in a murine lung cancer model. Effector cells peaked 7 to 10 days after the last vaccination. Compared with traditional 2-week-interval immunization strategies, antigen-specific cytolysis and INF-γ secretion were significantly enhanced under the fast vaccination approach. As a result, the rapidly administered DNA vaccine elicited stronger and more prompt antitumor effects. The probable underlying mechanism of fast immunization was the accumulation of CD8+CD11c+ antigen-presenting cells at the injection site, which enhanced subsequent antigen presentation. In conclusion, the fast DNA vaccination strategy shortened vaccination time to 5 days and elicited a stronger antitumor immune response.
Highlights
DNA vaccines are a promising cancer immunotherapeutic strategy, offering advantages such as a favorable safety profile, and simple preparation and storage requirements [1, 2]
The upregulation of a series of chemokines was observed in muscle or the ipsilateral inguinal lymph nodes throughout 0–168 h after DNA vaccine administration (Figure 1A)
Within the ipsilateral inguinal lymph nodes, of immature dendritic cells (DCs) (iDC)-recruiting chemokines Ccl3/Ccl4/Ccl5/Ccl20, only Ccl20 exhibited a modest 1.294-fold increase at the 72-h time point, while low expression was observed for the rest (Figure 1C). mature DC (mDC)-recruiting Ccl21 was considerably upregulated 12.21-fold at the 9-h point, 9.30-fold at the 48-h point, 10.24-fold at the 72-h point, and 4.38-fold at the 96-h point (Figure 1C)
Summary
DNA vaccines are a promising cancer immunotherapeutic strategy, offering advantages such as a favorable safety profile, and simple preparation and storage requirements [1, 2]. In the current vaccination strategies, an interval of at least 2 weeks is recommended between doses, requiring at least a month or more for the generation of a robust immune response [4,5,6]. Fast Cancer DNA Vaccination Strategy response induction via DNA vaccine therapy is generally considered time-consuming [7, 8]. This slow process struggles to effectively counteract rapid cancer progression [9]. A fast DNA vaccination strategy that can efficiently elicit immune responses has not been established
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