BCG vaccination provides protection against IAV but not SARS-CoV-2

TLDR

Innate immune memory evolved as a critical trait, and vaccines such as BCG can induce trained immunity that protects against heterologous pathogens. SARS‑CoV‑2 causes unique pulmonary vascular damage that allows dissemination to organs such as bone marrow, a key site for BCG‑mediated trained immunity, unlike influenza A virus. BCG vaccination markedly lowers morbidity and mortality from influenza A virus but offers no protection against SARS‑CoV‑2, likely because monocyte cytokine responses are robust to IAV yet minimal to SARS‑CoV‑2, indicating that BCG’s protective effect depends on viral pathogenesis and tissue tropism.

Abstract

Since the vast majority of species solely rely on innate immunity for host defense, it stands to reason that a critical evolutionary trait like immunological memory evolved in this primitive branch of our immune system. There is ample evidence that vaccines such as bacillus Calmette-Guérin (BCG) induce protective innate immune memory responses (trained immunity) against heterologous pathogens. Here we show that while BCG vaccination significantly reduces morbidity and mortality against influenza A virus (IAV), it fails to provide protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In contrast to IAV, SARS-CoV-2 infection leads to unique pulmonary vasculature damage facilitating viral dissemination to other organs, including the bone marrow (BM), a central site for BCG-mediated trained immunity. Finally, monocytes from BCG-vaccinated individuals mount an efficient cytokine response to IAV infection, while this response is minimal following SARS-CoV-2. Collectively, our data suggest that the protective capacity of BCG vaccination is contingent on viral pathogenesis and tissue tropism.