Bacillus Calmette-Guérin–induced trained immunity protects against SARS-CoV-2 challenge in K18-hACE2 mice
Bao-Zhong Zhang, … , Jian-Dong Huang, Hin Chu
Bao-Zhong Zhang, … , Jian-Dong Huang, Hin Chu
Published April 21, 2022
Citation Information: JCI Insight. 2022;7(11):e157393. https://doi.org/10.1172/jci.insight.157393.
View: Text | PDF
Research Article COVID-19 Infectious disease

Bacillus Calmette-Guérin–induced trained immunity protects against SARS-CoV-2 challenge in K18-hACE2 mice

Abstract

SARS-CoV-2 has been confirmed in over 450 million confirmed cases since 2019. Although several vaccines have been certified by the WHO and people are being vaccinated on a global scale, it has been reported that multiple SARS-CoV-2 variants can escape neutralization by antibodies, resulting in vaccine breakthrough infections. Bacillus Calmette-Guérin (BCG) is known to induce heterologous protection based on trained immune responses. Here, we investigated whether BCG-induced trained immunity protected against SARS-CoV-2 in the K18-hACE2 mouse model. Our data demonstrate that i.v. BCG (BCG-i.v.) vaccination induces robust trained innate immune responses and provides protection against WT SARS-CoV-2, as well as the B.1.617.1 and B.1.617.2 variants. Further studies suggest that myeloid cell differentiation and activation of the glycolysis pathway are associated with BCG-induced training immunity in K18-hACE2 mice. Overall, our study provides the experimental evidence that establishes a causal relationship between BCG-i.v. vaccination and protection against SARS-CoV-2 challenge.

Authors

Bao-Zhong Zhang, Huiping Shuai, Hua-Rui Gong, Jing-Chu Hu, Bingpeng Yan, Terrence Tsz-Tai Yuen, Ye-Fan Hu, Chaemin Yoon, Xiao-Lei Wang, Yuxin Hou, Xuansheng Lin, Xiner Huang, Renhao Li, Yee Man Au-Yeung, Wenjun Li, Bingjie Hu, Yue Chai, Ming Yue, Jian-Piao Cai, Guang Sheng Ling, Ivan Fan-Ngai Hung, Kwok-Yung Yuen, Jasper Fuk-Woo Chan, Jian-Dong Huang, Hin Chu

×

Figure 4

BCG-i.v. vaccination promotes myelopoiesis in BM cells.

Options: View larger image (or click on image) Download as PowerPoint
BCG-i.v. vaccination promotes myelopoiesis in BM cells. (A) Schematic re...
(A) Schematic representation of the experimental procedure for RNA-seq or flow cytometry. K18-hACE2 mice were i.v.- or s.c.-inoculated with BCG. Mice in the control group were injected i.v. with PBS. Mice BM cells were collected on day 45 after BCG vaccination or PBS treatment and processed to RNA-seq or flow cytometry. (B) The profile of differentially expressed genes comparing BM cells from BCG-i.v.–vaccinated and control-vaccinated mice. (C) Top 10 most strongly enriched GO biology process terms among upregulated genes in BCG-i.v.–immunized mice. (D) Gene expression levels of IFN response genes and markers of myeloid and lymphoid cells. (E) Representative FACS blots of the frequencies of MPP3 and MPP4 populations in nonvaccinated (PBS-i.v.), BCG-s.c.–, or BCG-i.v.–vaccinated mice (left to right). (F) The quantification of the total cell numbers (left panel) and relative cell percentage (right panel) of MPP3 and MPP4 (among all MPPs) in nonvaccinated (PBS-i.v.), BCG-s.c.–, or BCG-i.v.–vaccinated mice. Data are presented as mean ± SD. Statistical significance was calculated using 2-way ANOVA test (***P < 0.001). (G) Impact of BCG-i.v. vaccination on the polarization of BM cells toward the myeloid lineage.