Lassa virus (LASV) causes severe hemorrhagic fever with high mortality, yet no vaccine currently exists. Antibodies targeting viral attachment proteins are crucial for protection against many viral infections. However, the envelope glycoprotein (GP)−1 of LASV elicits weak antibody responses due to extensive glycan shielding. Here, we explored a novel vaccine strategy to enhance humoral immunity against LASV GP1. Using structural information, we designed a recombinant GP1 immunogen, and then encapsulated it into oxidation-sensitive polymersomes (PS) as nanocarriers that promote intracellular MHCII loading. Mice immunized with adjuvanted PS (LASV GP1) showed superior humoral responses than free LASV GP1, including antibodies with higher binding affinity to virion GP1, increased levels of polyfunctional anti-viral CD4 T cells, and IgG-secreting B cells. PS (LASV GP1) elicited a more diverse epitope repertoire of anti-viral IgG. Together, these data demonstrate the potential of our nanocarrier vaccine platform for generating virus-specific antibodies against weakly immunogenic viral antigens.

拉沙病毒（LASV）引起严重的出血热，死亡率很高，但目前尚无疫苗。靶向病毒附着蛋白的抗体对于预防许多病毒感染至关重要。但是，由于广泛的聚糖屏蔽，LASV的包膜糖蛋白（GP）-1引起较弱的抗体反应。在这里，我们探索了一种新型疫苗策略，以增强针对LASV GP1的体液免疫。利用结构信息，我们设计了重组GP1免疫原，然后将其封装到氧化敏感性多聚体（PS）中，作为促进细胞内MHCII负载的纳米载体。用佐剂PS（LASV GP1）免疫的小鼠表现出比游离LASV GP1更好的体液反应，包括对病毒体GP1具有更高结合亲和力的抗体，多功能抗病毒CD4 T细胞水平升高，和分泌IgG的B细胞。PS（LASV GP1）引发了更多的抗病毒IgG抗原决定簇。总之，这些数据证明了我们的纳米载体疫苗平台在产生针对弱免疫原性病毒抗原的病毒特异性抗体方面的潜力。