PDF(Pubmed)
Abstract：
This study focuses on the development and characterization of an intranasal vaccine platform using adjuvanted nanoparticulate delivery of swine influenza A virus (SwIAV). The vaccine employed whole inactivated H1N2 SwIAV as an antigen and STING-agonist ADU-S100 as an adjuvant, with both surface adsorbed or encapsulated in mannose-chitosan nanoparticles (mChit-NPs). Optimization of mChit-NPs included evaluating size, zeta potential, and cytotoxicity, with a 1:9 mass ratio of antigen to NP demonstrating high loading efficacy and non-cytotoxic properties suitable for intranasal vaccination. In a heterologous H1N1 pig challenge trial, the mChit-NP intranasal vaccine induced cross-reactive sIgA antibodies in the respiratory tract, surpassing those of a commercial SwIAV vaccine. The encapsulated mChit-NP vaccine induced high virus-specific neutralizing antibody and robust cellular immune responses, while the adsorbed vaccine elicited specific high IgG and hemagglutinin inhibition antibodies. Importantly, both the mChit-NP vaccines reduced challenge heterologous viral replication in the nasal cavity higher than commercial swine influenza vaccine. In summary, a novel intranasal mChit-NP vaccine platform activated both the arms of the immune system and is a significant advancement in swine influenza vaccine design, demonstrating its potential effectiveness for pig immunization.
摘要：
这项研究的重点是使用佐剂纳米颗粒递送猪甲型流感病毒（SwIAV）的鼻内疫苗平台的开发和表征。该疫苗采用全灭活的H1N1N2SwIAV作为抗原，STING激动剂ADU-S100作为佐剂，两个表面都吸附或包封在甘露糖-壳聚糖纳米颗粒(mChit-NP)中。mChit-NP的优化包括评估尺寸，zeta电位,和细胞毒性，抗原与NP的质量比为1:9,证明了适用于鼻内接种的高负载功效和非细胞毒性特性。在一项异源H1N1猪攻击试验中，mChit-NP鼻内疫苗在呼吸道诱导交叉反应的sIgA抗体，超过那些商业SwIAV疫苗。封装的mChit-NP疫苗诱导高病毒特异性中和抗体和强大的细胞免疫反应，而吸附疫苗引发特异性高IgG和血凝素抑制抗体。重要的是,与商业猪流感疫苗相比,两种mChit-NP疫苗降低了鼻腔中攻击异源病毒的复制。总之,一种新型鼻内mChit-NP疫苗平台激活了免疫系统的两个分支，是猪流感疫苗设计的一项重大进展，证明其对猪免疫的潜在有效性。
