Naturally occurring self-assembling ferritin nanoparticles have become widely appreciated for vaccine design. In this study, an apoferritin (AFt) nanocage was used as a carrier to construct a biomimetic influenza vaccine by encapsulating a conserved internal nucleoprotein (NP) antigen peptide inside the nanocage, followed by chemically conjugating the surface antigen hemagglutinin (HA) protein on the outer surface of the AFt. Benefiting from the excellent thermal stability and thermallyassociated structural flexibility of the AFt nanocages, a novel temperature shift based encapsulation process was proposed and proved efficient for encapsulation of the NP peptides. On average, about 18 NPs were encapsulated and 1.6 HA antigens were conjugated in each of the HA-AFt+NP dual-antigen influenza vaccines. Upon immunization in mice, the HA-AFt+NP vaccine elicited both HA and NP-specific antibodies, and conferred complete protection against a lethal infection of both homologous PR8 H1N1 and heterologous A/FM/1/47 (FM1, H1N1) strains, while the HA-AFt conjugate vaccine without encapsulated NP antigen only conferred 60% protection against the FM1 H1N1 viral challenge. The potential cross-protective effect of the HA-AFt+NP vaccine was further demonstrated by significant specific hemagglutination inhibition (HAI) titers in serum of the immunized mice against heterologous A/Hong Kong/4801/2014 (H3N2) viral strain, which was about 3-fold of that induced by HA antigen and 2-fold of the HA-AFt conjugate vaccine. This biomimetic HA-AFt+NP conjugate vaccine, therefore, may represent a new strategy for developing a potential universal influenza vaccine without the need of any adjuvant, and further broaden the application of AFt nanocages in the areas of vaccine development and delivery system.

中文翻译：

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载铁蛋白-血凝素结合有来自流感病毒的封装的核蛋白抗原肽的疫苗，可增强交叉保护。

天然存在的自组装铁蛋白纳米颗粒已被广泛用于疫苗设计。在这项研究中，载铁蛋白（AFt）纳米笼被用作载体，通过将保守的内部核蛋白（NP）抗原肽包封在纳米笼中，然后化学偶联表面上的表面血凝素（HA）蛋白来构建仿生流感疫苗。 AFt的外表面。得益于AFt纳米笼的出色的热稳定性和与热相关的结构柔性，提出了一种新颖的基于温度变化的包封方法，并被证明对于NP肽的包封有效。平均而言，在每种HA-AFt + NP双抗原流感疫苗中，均封装了约18个NP，并偶联了1.6种HA抗原。小鼠免疫后 HA-AFt + NP疫苗可同时引起HA和NP特异性抗体，并提供完全保护，以防止同源PR8 H1N1和异源A / FM / 1/47（FM1，H1N1）菌株的致死性感染，而HA-AFt没有封装的NP抗原的复合疫苗仅针对FM1 H1N1病毒攻击提供了60％的保护。HA-AFt + NP疫苗的潜在交叉保护作用进一步通过免疫小鼠血清中针对异源A / Hong Kong / 4801/2014（H3N2）病毒株的显着特异性血凝抑制（HAI）滴度证实。大约是HA抗原诱导的3倍，是HA-AFt结合疫苗的2倍。因此，这种仿生HA-AFt + NP偶联疫苗可能代表了开发潜在的通用流感疫苗而无需任何佐剂的新策略，