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

Abstract

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.

Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomised ascending dose phase I trial

“…Alternatively, delivery of other adenovirus-vectored vaccines to the lower airways by nebulization has been reported to achieve good immunogenicity. 4 , 45 , 46 A study of nebulized ChAdOx1 nCoV-19 is ongoing (NCT05007275), but nebulization may be less practical than IN delivery for mass vaccination.…”

Development of Equine Polyclonal Antibodies as a Broad-Spectrum Therapy Against SARS-CoV-2 Variants

“…The proposed administration routine of our equine anti-RBD pAbs includes both inhalation and injection in future clinical applications. The inhalation method exhibit various advantages on prophylactic and therapeutic applications (38). For example, inhalation can block the transmission route among individuals by attaching the antibodies on the respiratory tract surfaces, which can prevent virus invasion into the airway cells and also prevent the virus from being coughed up by the patient.…”

Design Considerations for Intratracheal Delivery Devices to Achieve Proof-of-Concept Dry Powder Biopharmaceutical Delivery in Mice

“…All experimental procedures and animal handling protocols were approved and in accordance with the guidelines of McMaster University’s Animal Research and Ethics Board. To confirm suitability of our excipient blend and quantify in vivo bioactivity of the adenovirus following spray drying, reconstituted spray dried powder was administered as a liquid control via intratracheal inoculation using a previously described technique [ 18 ]. Following anaesthetization with isoflurane, mice were hung by their teeth on a string attached to a 45° intubation board while the tongue is held to the side to expose the trachea and prevent swallowing.…”

“…To deliver spray dried powder using each dosator design, endotracheal intubation was conducted using a previously described protocol in which the anesthetized mouse was suspended on a 45° intubation board by its teeth [ 18 ]. Once the tracheal opening was located, a P200 pipette containing 100 µL of water was inserted into the trachea to confirm the correct location based on the movement of the air gap during aspiration.…”