Pandey Bhawana, Wang Zhengying, Jimenez Angela, Bhatia Eshant, Jain Ritika, Beach Alexander, Maniar Drishti, Hosten Justin, O'Farrell Laura, Vantucci Casey, Hur David, Noel Richard, Ringquist Rachel, Smith Clinton, Ochoa Miguel A, Roy Krishnendu
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Adv Sci (Weinh). 2024 Dec;11(45):e2402792. doi: 10.1002/advs.202402792. Epub 2024 Oct 1.
Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters can overcome the shortcomings of parenteral vaccines and enhance pre-existing systemic immunity. Here, a new protein subunit nanovaccine is developed by utilizing dual-adjuvanted (RIG-I: PUUC RNA and TLR-9: CpG DNA) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) along with SARS-CoV-2 S1 trimer protein, that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL subunit nanovaccine, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lungs and showed robust systemic humoral immunity. Interestingly, as a purely intranasal subunit vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. The data suggest that PUUC+CpG PAL subunit nanovaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.
现有的肠胃外注射用SARS-CoV-2疫苗仅能产生有限的黏膜反应，而黏膜反应对于减少传播和实现灭菌免疫至关重要。设计合理的黏膜加强针可以克服肠胃外注射疫苗的缺点，并增强已有的全身免疫力。在此，一种新的蛋白质亚单位纳米疫苗被研发出来，它利用双佐剂（RIG-I：PUUC RNA和TLR-9：CpG DNA）多糖-氨基酸-脂质纳米颗粒（PAL-NPs）以及SARS-CoV-2 S1三聚体蛋白，可以通过肌肉注射（IM）和鼻内注射（IN）两种方式给药，以产生平衡的黏膜-全身SARS-CoV-2免疫。接受IM-Prime PUUC+CpG PAL亚单位纳米疫苗肌肉注射，随后进行鼻内加强注射的小鼠，在肺部产生了高水平的IgA、IgG和细胞免疫，并表现出强大的全身体液免疫。有趣的是，作为一种单纯的鼻内亚单位疫苗（IN-Prime/IN-Boost），PUUC+CpG PAL-NPs诱导的肺部特异性T细胞免疫比IM-Prime/IN-Boost更强，且IgA和中和抗体水平相当，尽管全身抗体反应较低，这表明SARS-CoV-2疫苗的完全黏膜给药途径也可能是可行的。数据表明，PUUC+CpG PAL亚单位纳米疫苗是产生SARS-CoV-2特异性黏膜免疫的一个有前景的候选疫苗。
