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

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

Microbiology And Immunology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	107612
Journal	iScience
Volume	26
Issue number	9
DOIs	https://doi.org/10.1016/j.isci.2023.107612
State	Published - Sep 15 2023

Keywords

Biological sciences
Immune response
Immunology
Microbiology

ASJC Scopus subject areas

General

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10.1016/j.isci.2023.107612

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Perera, D. J., Domenech, P., Babuadze, G. G., Naghibosadat, M., Alvarez, F., Koger-Pease, C., Labrie, L., Stuible, M., Durocher, Y., Piccirillo, C. A., Lametti, A., Fiset, P. O., Elahi, S. M., Kobinger, G. P., Gilbert, R., Olivier, M., Kozak, R., Reed, M. B., & Ndao, M. (2023). BCG administration promotes the long-term protection afforded by a single-dose intranasal adenovirus-based SARS-CoV-2 vaccine. iScience, 26(9), Article 107612. https://doi.org/10.1016/j.isci.2023.107612

Perera, DJ, Domenech, P, Babuadze, GG, Naghibosadat, M, Alvarez, F, Koger-Pease, C, Labrie, L, Stuible, M, Durocher, Y, Piccirillo, CA, Lametti, A, Fiset, PO, Elahi, SM, Kobinger, GP, Gilbert, R, Olivier, M, Kozak, R, Reed, MB & Ndao, M 2023, 'BCG administration promotes the long-term protection afforded by a single-dose intranasal adenovirus-based SARS-CoV-2 vaccine', iScience, vol. 26, no. 9, 107612. https://doi.org/10.1016/j.isci.2023.107612

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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+ TREG 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.",

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AU - Babuadze, George Giorgi

AU - Naghibosadat, Maedeh

AU - Alvarez, Fernando

AU - Koger-Pease, Cal

AU - Labrie, Lydia

AU - Stuible, Matthew

AU - Durocher, Yves

AU - Piccirillo, Ciriaco A.

AU - Lametti, André

AU - Fiset, Pierre Olivier

AU - Elahi, Seyyed Mehdy

AU - Kobinger, Gary P.

AU - Gilbert, Rénald

AU - Olivier, Martin

AU - Kozak, Robert

AU - Reed, Michael B.

AU - Ndao, Momar

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AB - 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+ TREG 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.

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

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