PDF(Pubmed)
Abstract：
Enhancing influenza vaccine cross-protection is imperative to alleviate the significant public health burden of influenza. Heterologous sequential immunization may synergize diverse vaccine formulations and routes to improve vaccine potency and breadth. Here we investigate the effects of immunization strategies on the generation of cross-protective immune responses in female Balb/c mice, utilizing mRNA lipid nanoparticle (LNP) and protein-based PHC nanoparticle vaccines targeting influenza hemagglutinin. Our findings emphasize the crucial role of priming vaccination in shaping Th bias and immunodominance hierarchies. mRNA LNP prime favors Th1-leaning responses, while PHC prime elicits Th2-skewing responses. We demonstrate that cellular and mucosal immune responses are pivotal correlates of cross-protection against influenza. Notably, intranasal PHC immunization outperforms its intramuscular counterpart in inducing mucosal immunity and conferring cross-protection. Sequential mRNA LNP prime and intranasal PHC boost demonstrate optimal cross-protection against antigenically drifted and shifted influenza strains. Our study offers valuable insights into tailoring immunization strategies to optimize influenza vaccine effectiveness.
摘要：
加强流感疫苗交叉保护是减轻流感重大公共卫生负担的当务之急。异源序贯免疫可以协同多种疫苗制剂和途径以提高疫苗效力和广度。在这里，我们研究了免疫策略对雌性Balb/c小鼠产生交叉保护性免疫应答的影响，利用针对流感血凝素的mRNA脂质纳米颗粒（LNP）和基于蛋白质的PHC纳米颗粒疫苗。我们的发现强调了启动疫苗接种在塑造Th偏见和免疫优势等级中的关键作用。mRNALNP主要有利于Th1倾向反应，而PHC素数引发Th2偏斜反应。我们证明，细胞和粘膜免疫反应是抗流感交叉保护的关键相关因素。值得注意的是,鼻内PHC免疫在诱导粘膜免疫和赋予交叉保护方面优于其肌内对应物。顺序的mRNALNP引发和鼻内PHC加强显示针对抗原漂移和转移的流感毒株的最佳交叉保护。我们的研究为定制免疫策略以优化流感疫苗的有效性提供了有价值的见解。
