Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
J Control Release. 2021 Feb 10;330:529-539. doi: 10.1016/j.jconrel.2020.12.031. Epub 2020 Dec 20.
The current health crisis of corona virus disease 2019 (COVID-19) highlights the urgent need for vaccine systems that can generate potent and protective immune responses. Protein vaccines are safe, but conventional approaches for protein-based vaccines often fail to elicit potent and long-lasting immune responses. Nanoparticle vaccines designed to co-deliver protein antigens and adjuvants can promote their delivery to antigen-presenting cells and improve immunogenicity. However, it remains challenging to develop vaccine nanoparticles that can preserve and present conformational epitopes of protein antigens for induction of neutralizing antibody responses. Here, we have designed a new lipid-based nanoparticle vaccine platform (NVP) that presents viral proteins (HIV-1 and SARS-CoV-2 antigens) in a conformational manner for induction of antigen-specific antibody responses. We show that NVP was readily taken up by dendritic cells (DCs) and promoted DC maturation and antigen presentation. NVP loaded with BG505.SOSIP.664 (SOSIP) or SARS-CoV-2 receptor-binding domain (RBD) was readily recognized by neutralizing antibodies, indicating the conformational display of antigens on the surfaces of NVP. Rabbits immunized with SOSIP-NVP elicited strong neutralizing antibody responses against HIV-1. Furthermore, mice immunized with RBD-NVP induced robust and long-lasting antibody responses against RBD from SARS-CoV-2. These results suggest that NVP is a promising platform technology for vaccination against infectious pathogens.
当前 2019 年冠状病毒病（COVID-19）的健康危机突出表明，迫切需要能够产生有效和保护性免疫应答的疫苗系统。蛋白质疫苗是安全的，但传统的蛋白质疫苗方法往往不能引起有效和持久的免疫应答。旨在共同递送蛋白质抗原和佐剂的纳米颗粒疫苗可以促进它们递送至抗原呈递细胞并提高免疫原性。然而，开发能够保存和呈现蛋白质抗原构象表位以诱导中和抗体应答的疫苗纳米颗粒仍然具有挑战性。在这里，我们设计了一种新的基于脂质的纳米颗粒疫苗平台（NVP），该平台以构象方式呈现病毒蛋白（HIV-1 和 SARS-CoV-2 抗原），以诱导抗原特异性抗体应答。我们表明，NVP 可被树突状细胞（DC）轻易摄取，并促进 DC 成熟和抗原呈递。负载 BG505.SOSIP.664（SOSIP）或 SARS-CoV-2 受体结合域（RBD）的 NVP 可被中和抗体轻易识别，表明抗原在 NVP 表面的构象显示。用 SOSIP-NVP 免疫的兔子产生了针对 HIV-1 的强烈中和抗体应答。此外，用 RBD-NVP 免疫的小鼠诱导了针对 SARS-CoV-2 的 RBD 的强大和持久的抗体应答。这些结果表明，NVP 是一种有前途的用于针对传染病病原体的疫苗接种的平台技术。
