iScience (Sep 2023)

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

Journal volume & issue
Vol. 26, no. 9
p. 107612

Abstract

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Summary: 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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