Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York, USA.
Texas Biomedical Research Institutegrid.250889.e, San Antonio, Texas, USA.
J Virol. 2022 Oct 12;96(19):e0100622. doi: 10.1128/jvi.01006-22. Epub 2022 Sep 15.
Intranasal vaccination offers the potential advantage of needle-free prevention of respiratory pathogens such as influenza viruses with induction of mucosal immune responses. Optimal design of adjuvants and antigen delivery vehicles for intranasal delivery has not yet been well established. Here, we report that an adjuvant-containing nanoliposome antigen display system that converts soluble influenza hemagglutinin antigens into nanoparticles is effective for intranasal immunization. Intranasal delivery of nanoliposomes in mice delivers the particles to resident immune cells in the respiratory tract, inducing a mucosal response in the respiratory system as evidenced by nasal and lung localized IgA antibody production, while also producing systemic IgG antibodies. Intranasal vaccination with nanoliposome particles decorated with nanogram doses of hemagglutinin protected mice from homologous and heterologous H3N2 and H1N1 influenza virus challenge. A self-assembling influenza virus vaccine platform that seamlessly converts soluble antigens into nanoparticles is demonstrated with various H1N1 and H3N2 influenza antigens to protect mice against influenza virus challenge following intranasal vaccination. Mucosal immune responses following liposome delivery to lung antigen-presenting cells are demonstrated.
鼻腔内接种具有无需注射即可预防流感病毒等呼吸道病原体的潜在优势,可诱导黏膜免疫应答。但尚未很好地确定用于鼻腔内传递的佐剂和抗原传递载体的最佳设计。在这里,我们报告了一种含有佐剂的纳米脂质体抗原展示系统,可将可溶性流感血凝素抗原转化为纳米颗粒,该系统可有效用于鼻腔内免疫接种。在小鼠中进行的鼻腔内纳米脂质体的传递将颗粒递送至呼吸道中的常驻免疫细胞,在呼吸道中引起黏膜反应,表现为鼻和肺局部 IgA 抗体的产生,同时也产生系统 IgG 抗体。用带有纳米克剂量血凝素的纳米脂质体颗粒进行鼻腔内接种可保护小鼠免受同源和异源 H3N2 和 H1N1 流感病毒的攻击。展示了一种自组装的流感病毒疫苗平台,可将可溶性抗原无缝转化为纳米颗粒,并用各种 H1N1 和 H3N2 流感抗原进行修饰,以在鼻腔内接种疫苗后保护小鼠免受流感病毒的攻击。还证明了脂质体向肺抗原呈递细胞传递后的黏膜免疫应答。