Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2

作者：Afkhami, Sam; D'Agostino, Michael R.; Zhang, Ali; Stacey, Hannah D.; Marzok, Art; Kang, Alisha; Singh, Ramandeep; Bavananthasivam, Jegarubee; Ye, Gluke; Luo, Xiangqian; Wang, Fuan; Ang, Jann C.; Zganiacz, Anna; Sankar, Uma; Kazhdan, Natallia; Koenig, Joshua F. E.; Phelps, Allyssa; Gameiro, Steven F.; Tang, Shangguo; Jordana, Manel; Wan, Yonghong; Mossman, Karen L.; Jeyanathan, Mangalakumari; Gillgrass, Amy; Medina, Maria Fe C.; Smaill, Fiona; Lichty, Brian D.^*

来源：Cell, 2022, 185(5): 896-+.

DOI：10.1016/j.cell.2022.02.005

• T-CELLS
• IMMUNIZATION
• IMMUNITY
• INTRANASAL
• MACROPHAGES
• TRACTS
• ROUTE

The emerging SARS-CoV-2 variants of concern (VOCs) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, we evaluated Ad-vectored trivalent COVID-19 vaccines expressing spike-1, nucleocapsid, and RdRp antigens in murine models. We show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. We further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Our findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC.

• 单位
  1; 南方医科大学