BCG administration promotes the long-term protection afforded by a single-dose intranasal adenovirus-based SARS-CoV-2 vaccine

Dilhan J Perera; Pilar Domenech; George Giorgi Babuadze; Maedeh Naghibosadat; Fernando Alvarez; Cal Koger-Pease; Lydia Labrie; Matthew Stuible; Yves Durocher; Ciriaco A Piccirillo; André Lametti; Pierre Olivier Fiset; Seyyed Mehdy Elahi; Gary P Kobinger; Rénald Gilbert; Martin Olivier; Robert Kozak; Michael B Reed; Momar Ndao

doi:10.1016/j.isci.2023.107612

BCG administration promotes the long-term protection afforded by a single-dose intranasal adenovirus-based SARS-CoV-2 vaccine

iScience. 2023 Aug 11;26(9):107612. doi: 10.1016/j.isci.2023.107612. eCollection 2023 Sep 15.

Authors

Dilhan J Perera^{1

2}, Pilar Domenech^{2

3}, George Giorgi Babuadze^{4

5}, Maedeh Naghibosadat⁴, Fernando Alvarez^{2

6}, Cal Koger-Pease^{1

2}, Lydia Labrie^{2

6}, Matthew Stuible⁷, Yves Durocher⁷, Ciriaco A Piccirillo^{1

2

6}, André Lametti⁸, Pierre Olivier Fiset⁸, Seyyed Mehdy Elahi⁷, Gary P Kobinger⁹, Rénald Gilbert⁷, Martin Olivier^{1

2

6}, Robert Kozak^{4

10}, Michael B Reed^{2

3}, Momar Ndao^{1

2

6

11}

Affiliations

¹ Division of Experimental Medicine, McGill University, Montréal, QC, Canada.
² Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montréal, QC, Canada.
³ McGill International TB Centre, McGill University, Montréal, QC, Canada.
⁴ Department of Biological Sciences, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
⁵ Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA.
⁶ Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.
⁷ Department of Production Platforms & Analytics, Human Health Therapeutics Research Center, National Research Council Canada, Montréal, QC, Canada.
⁸ Department of Pathology, McGill University, Montréal, QC, Canada.
⁹ Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada.
¹⁰ Department of Laboratory Medicine and Molecular Diagnostics, Division of Microbiology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹¹ National Reference Centre for Parasitology, McGill University Health Centre, Montréal, QC, Canada.

Abstract

Recent publications have explored intranasal (i.n.) adenovirus-based (Ad) vaccines as an effective strategy for SARS-CoV-2 in pre-clinical models. However, the effects of prior immunizations and infections have yet to be considered. Here, we investigate the immunomodulatory effects of Mycobacterium bovis BCG pre-immunization followed by vaccination with an S-protein-expressing i.n. Ad, termed Ad(Spike). While i.n. Ad(Spike) retains some protective effect after 6 months, a single administration of BCG-Danish prior to Ad(Spike) potentiates its ability to control viral replication of the B.1.351 SARS-CoV-2 variant within the respiratory tract. Though BCG-Danish did not affect Ad(Spike)-generated humoral immunity, it promoted the generation of cytotoxic/Th1 responses over suppressive FoxP3⁺ T_REG cells in the lungs of infected mice. Thus, this vaccination strategy may prove useful in limiting future pandemics by potentiating the long-term efficacy of mucosal vaccines within the context of the widely distributed BCG vaccine.

Keywords: Biological sciences; Immune response; Immunology; Microbiology.