Journal of Vaccine Research 2024, Vol.14, No.6, 297-306 http://medscipublisher.com/index.php/jvr 300 subtypes. Compared with traditional HA/NA vaccines, the immune response induced by such antigens not only lasts for a long time but also has broad-spectrum protective characteristics. For example, nasal vaccination with NP vaccine can activate the multifunctional CD4 T cell population in the lungs, achieving the dual effects of early protection and continuous defense (Nelson et al., 2021). This strategy has a dual advantage: it can cover multiple influenza subtypes and also reduce the need for annual vaccine updates. Because T cells targeting NP and matrix proteins can recognize strains with significant genetic differences, they have become ideal targets for universal vaccines (Lo et al., 2021). 4.2 Progress in new delivery systems Cutting-edge vaccine technologies are enhancing cellular immunity through innovative delivery methods. Virus-like particles (VLPs), as a typical representative, their biomimetic structure can efficiently present conserved antigens and simultaneously activate the responses of CD4 and CD8 T cells (Landry et al., 2014). This non-replicative vector has achieved comprehensive immune activation on the premise of ensuring safety. The "primary immunization - booster" combined strategy demonstrates unique value: Through sequential vaccination by intramuscular injection and nasal spray, a memory T cell (TRM) defense line can be established in the respiratory tract. This hierarchical immunity model can form a rapid response force at the infection portal, significantly enhancing the efficiency of early defense (Figure 2) (Kong et al., 2023). Figure 2 NP-specific vaccination via “prime-and-deploy” strategy provides protective immunity against influenza infection (Adopted from Kong et al., 2023) Image caption: BALB/c mice were immunized with rAd/A-NP (2×107 PFU) or rAd/B-NP (1×108 PFU) via the i.m. route, and the “prime-and-deploy” groups were administered rAd/mock (5×107 PFU) via the i.n. route 6 days after immunization. (A) Schematic of experimental progression. (B) Weight loss and survival rate 14 days after 10 LD50 A/PR8 challenge. (C) Weight loss and survival rate 14 days after 10 LD50 B/Yamagata challenge. Data are presented as the mean ± SEM based on n=8. (D) Viral replication levels were determined by plaque assay on MDCK cells in supernatant of lung homogenates harvested on day 5 post-challenge. Bars show geometric mean titer ± SEM of 5 mice per group. Statistical analysis of the Kaplan-Meier survival curves after challenge was conducted by log-rank analysis. *p<0.05 (unpaired t-test) (Adopted from Kong et al., 2023)
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