Differential Biodistribution of Adenoviral-Vectored Vaccine Following Intranasal and Endotracheal Deliveries Leads to Different Immune Outcomes

Frontiers in Immunology

Immunology

Michael R. Thompson¹  Michael R. D’Agostino²  Matthew S. Miller²  Anna Zganiacz³  Zhou Xing³  Sam Afkhami³  Vidthiya Jeyanathan³  Mangalakumari Jeyanathan³  Xueya Feng³ 

[1] Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada;McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, Hamilton, ON, Canada;Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON, Canada;McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, Hamilton, ON, Canada;Department of Medicine, McMaster University, Hamilton, ON, Canada;

关键词: respiratory mucosal immunization;    intranasal;    endotracheal;    biodistribution;    Adenovirus-vectored vaccine;    Tuberculosis;    mucosal immunity;    T cells;   

DOI  :  10.3389/fimmu.2022.860399

 received in 2022-01-22, accepted in 2022-05-11,  发布年份 2022

来源: Frontiers

【 摘 要 】

Infectious diseases of the respiratory tract are one of the top causes of global morbidity and mortality with lower respiratory tract infections being the fourth leading cause of death. The respiratory mucosal (RM) route of vaccine delivery represents a promising strategy against respiratory infections. Although both intranasal and inhaled aerosol methods have been established for human application, there is a considerable knowledge gap in the relationship of vaccine biodistribution to immune efficacy in the lung. Here, by using a murine model and an adenovirus-vectored model vaccine, we have compared the intranasal and endotracheal delivery methods in their biodistribution, immunogenicity and protective efficacy. We find that compared to intranasal delivery, the deepened and widened biodistribution in the lung following endotracheal delivery is associated with much improved vaccine-mediated immunogenicity and protection against the target pathogen. Our findings thus support further development of inhaled aerosol delivery of vaccines over intranasal delivery for human application.

【 授权许可】

Unknown   
Copyright © 2022 Jeyanathan, Afkhami, D’Agostino, Zganiacz, Feng, Miller, Jeyanathan, Thompson and Xing