Induction of lung mucosal immunity by a next-generation inhaled aerosol COVID-19 vaccine: an open-label, multi-arm phase 1 clinical trial

Mangalakumari Jeyanathan, Sam Afkhami, Michael R. D’Agostino, Imran Satia, Dominik K. Fritz, Kate Miyasaki, Jann C. Ang, Anna Zganiacz, Karen J. Howie, Marilyn Swinton, Emilio Aguirre, Michael B. Zheng, Natallia Kazhdan, Anna Dvorkin-Gheva, Lawrence Mbuagbaw, Maria Fe C. Medina, Nermin Diab, Danica L. Brister, Gail M. Gauvreau, Brian D. Lichty (), Matthew S. Miller (), Fiona Smaill () and Zhou Xing ()
Additional contact information
Mangalakumari Jeyanathan: McMaster University
Sam Afkhami: McMaster University
Michael R. D’Agostino: McMaster University
Imran Satia: McMaster University
Dominik K. Fritz: McMaster University
Kate Miyasaki: McMaster University
Jann C. Ang: McMaster University
Anna Zganiacz: McMaster University
Karen J. Howie: McMaster University
Marilyn Swinton: McMaster University
Emilio Aguirre: McMaster University
Michael B. Zheng: McMaster University
Natallia Kazhdan: McMaster University
Anna Dvorkin-Gheva: McMaster University
Lawrence Mbuagbaw: McMaster University
Maria Fe C. Medina: McMaster University
Nermin Diab: McMaster University
Danica L. Brister: McMaster University
Gail M. Gauvreau: McMaster University
Brian D. Lichty: McMaster University
Matthew S. Miller: McMaster University
Fiona Smaill: McMaster University
Zhou Xing: McMaster University

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract The current COVID-19 vaccines are suboptimal against the evolving SARS-CoV-2 variants, particularly in high-risk populations. A next-generation vaccine strategy capable of effective induction of respiratory mucosal immunity remains to be clinically developed. Here, we report an open-label, multi-arm phase 1 study (NCT05094609) to evaluate a multi-antigenic COVID-19 vaccine delivered once via inhaled aerosol to the lung of intramuscular mRNA-vaccinated humans without or with prior SARS-CoV-2 infection (uninfected vs infected). Escalating doses of a human adenoviral (HuAd)-vectored or chimpanzee Ad (ChAd)-vectored vaccine are evaluated in the uninfected cohort. A selected Ad vaccine is further evaluated in the infected cohort. The safety is assessed as a primary outcome. Ag-specific immune responses (secondary outcome) are assessed in peripheral blood and in respiratory tract via bronchoscopy at baseline and at timepoint(s) post-vaccination. Eighteen-65-year-old, healthy participants who have received at least 3 doses of mRNA COVID-19 vaccine are enrolled with those vaccinated with any Ad-vectored COVID-19 vaccine excluded. At baseline, there is minimally detectable mucosal immunity in the lung of uninfected or infected humans. While all tested doses (1 × 105 to 1 × 108 TCID50) of HuAd and ChAd vaccines are safe, ChAd vaccine markedly outperforms the HuAd counterpart in immunogenicity. Thus, an optimal aerosol dose of ChAd vaccine induces the tripartite respiratory mucosal immunity consisting of T cell, trained innate and antibody immunity. Our study thus presents a promising next-generation aerosol COVID-19 vaccine strategy for further clinical development.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60726-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60726-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60726-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().