Abstract：
Mucosal vaccinations for respiratory pathogens provide effective protection as they stimulate localized cellular and humoral immunities at the site of infection. Currently, the major limitation of intranasal vaccination is using effective adjuvants capable of withstanding the harsh environment imposed by the mucosa. Herein, we describe the efficacy of using a unique biopolymer, N-dihydrogalactochitosan (GC), as a nasal mucosal vaccine adjuvant against respiratory infections. Specifically, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV), an MF-59 equivalent. In contrast to AV, intranasal application of GC induces a robust, systemic antigen-specific antibody response and increases the number of T cells in the cervical lymph nodes. Moreover, GC+S+NC-vaccinated animals were largely resistant to the lethal SARS-CoV-2 challenge and experienced drastically reduced morbidity and mortality, with animal weights and behavior returning to normal 22 days post-infection. In contrast, animals intranasally vaccinated with AV+S+NC experienced severe weight loss, mortality, and respiratory distress, with none surviving beyond 6 days post-infection. Our findings demonstrate that GC can serve as a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses. STATEMENT OF SIGNIFICANCE: We demonstrated that a unique biopolymer, N-dihydrogalactochitosan (GC), was an effective nasal mucosal vaccine adjuvant against respiratory infections. Specifically, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV). In contrast to AV, GC induces a robust, systemic antigen-specific antibody response and increases the number of T cells in the cervical lymph nodes. About 90 % of the GC+S+NC-vaccinated animals survived the lethal SARS-CoV-2 challenge and remained healthy 22 days post-infection, while the AV+S+NC-vaccinated animals experienced severe weight loss and respiratory distress, and all died within 6 days post-infection. Our findings demonstrate that GC is a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses.
摘要：
呼吸道病原体的粘膜疫苗接种提供了有效的保护，因为它们刺激感染部位的局部细胞和体液免疫。目前,鼻内疫苗接种的主要限制是使用能够承受粘膜施加的恶劣环境的有效佐剂。在这里，我们描述了使用独特的生物聚合物的功效，N-二氢半乳糖壳聚糖（GC），作为抗呼吸道感染的鼻粘膜疫苗佐剂。具体来说,我们将GC与重组SARS-CoV-2三聚体刺突（S）和核衣壳（NC）蛋白混合，以鼻内接种K18-hACE2转基因小鼠，与Addavax（AV）相比，相当于MF-59。与AV相比，鼻内应用GC诱导了一个强大的，全身抗原特异性抗体反应，并增加颈部淋巴结中T细胞的数量。此外，接种GC+S+NC的动物对致命的SARS-CoV-2攻击有很大的抵抗力，并且发病率和死亡率大大降低。动物体重和行为在感染后22天恢复正常。相比之下,动物鼻内接种AV+S+NC经历了严重的体重减轻，死亡率,呼吸窘迫,感染后6天以上无存活。我们的发现表明，GC可以作为抗SARS-CoV-2和潜在的其他呼吸道病毒的有效粘膜疫苗佐剂。重要声明：：我们证明了一种独特的生物聚合物，N-二氢半乳糖壳聚糖（GC），是一种有效的抗呼吸道感染的鼻粘膜疫苗佐剂。具体来说,我们将GC与重组SARS-CoV-2三聚体刺突（S）和核衣壳（NC）蛋白混合，以鼻内接种K18-hACE2转基因小鼠，与Addavax（AV）相比。与AV相比，GC诱导了一个强大的，全身抗原特异性抗体反应，并增加颈部淋巴结中T细胞的数量。大约90％的接种GCSNC的动物在致命的SARS-CoV-2攻击中幸存下来，并在感染后22天保持健康。而接种AV+S+NC的动物经历了严重的体重减轻和呼吸窘迫，全部在感染后6天内死亡。我们的发现表明，GC是针对SARS-CoV-2和潜在的其他呼吸道病毒的有效粘膜疫苗佐剂。
