JCI Insight Zhu Xuan/Huang Jiandong/Chen Fuhe team confirmed that BCG can induce training immunity against new coronavirus infection

iNature SARS-CoV-2 has resulted in more than 450 million confirmed cases since 2019
.

Although several vaccines have been certified by the World Health Organization and are being administered globally, multiple SARS-CoV-2 variants have been reported to escape neutralizing antibodies, leading to vaccine breakthrough infections
.

Bacille Calmette-Guérin (BCG) is known to induce heterologous protection based on a trained immune response
.

On April 21, 2022, Assistant Professor Zhu Xuan, Professor Huang Jiandong, and Clinical Associate Professor Chen Fuhe of the Faculty of Medicine of the University of Hong Kong communicated together (Associate Researcher Zhang Baozhong and Hu Jingchu of the Institute of Synthesis, Shenzhen Institute of Advanced Studies, Chinese Academy of Sciences, and Dr.
Shuai Huiping and Dr.
Gong Huarui of the Faculty of Medicine of the University of Hong Kong and Dr.
Yan Bingpeng, the co-first author of this achievement) published a research paper online in JCI Insight (IF: 8.
32) entitled "Bacillus Calmette–Guérin-induced trained immunityprotects against SARS-CoV-2 challenge in K18-hACE2 mice", This study investigated whether BCG-induced trained immunity protects against SARS-CoV-2 challenge in a K18-hACE2 mouse model
.

Data suggest that intravenous BCG vaccine induces a robust trained innate immune response and provides protection against wild-type SARS-CoV-2 as well as B.
1.
617.
1 and B.
1.
617.
2 variants
.

Further studies showed that activation of myeloid cell differentiation and glycolytic pathways were associated with BCG-induced training immunity in K18-hACE2 mice
.

Overall, this study provides experimental evidence for a causal relationship between intravenous BCG vaccination and protection against SARS-CoV-2 challenge
.

As of March 2022, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected more than 450 million people and caused more than 6.
01 million deaths
.

Data from preclinical development of vaccine candidates for SARS-CoV and MERS-CoV help to largely eliminate the need for initial discovery steps for a SARS-CoV-2 vaccine, saving considerable time
.

To date, the World Health Organization (WHO) has issued recommendations for the Pfizer-BioNTech, Moderna, AstraZeneca, Janssen COVID, Sinopharm and SinoVac vaccines
.

These vaccines have been approved by the World Health Organization for emergency use in different parts of the world
.

As of November 1, 2021, 7.
04 billion doses of vaccine have been administered worldwide, and 49.
4% of the global population has received at least one dose of the COVID-19 vaccine
.

Importantly, SARS-CoV-2 continues to evolve
.

To date, WHO has identified five variants of concern (VOC), including B.
1.
1.
7 (Alpha), B.
1.
351 (Beta), P.
1 (Gamma), B.
1.
617.
2 (Delta) and the most recent B.
1.
1.
529 (Omicron)
.

There is increasing evidence that VOCs spread faster than the original circulating strains and may alter disease manifestations
.

Multiple SARS-CoV-2 variants have been reported to escape antibody/vaccine neutralization, leading to breakthrough infections
.

Therefore, there is an urgent need to develop alternative immunization strategies
.

Figure: BCG can induce trained immunity against new coronavirus infection The innate immune system is the first line of defense against invading infections
.

It is mediated by the pattern recognition receptor (PRR) family, leading to the activation of myeloid (such as neutrophils, monocytes, and macrophages) and lymphoid immune cells (such as NK and γδ cells), thereby eliminating most infections in humans of pathogens
.

Adaptive immune responses (B and T cells) are only activated when the first line of defense is overwhelmed by a large number of pathogens
.

It has long been thought that only the adaptive immune system can build immune memory and defend against repeated infections
.

This lymphocyte property is the basis for vaccination against specific infections
.

However, recent studies have shown that following certain infections or vaccinations, innate immune cells can also exhibit adaptive traits that are functionally similar to the development of immune memory, also known as trained immunity
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Bacille Calmette-Guérin (BCG) is a live attenuated vaccine (LAV) developed in the early 20th century to combat tuberculosis
.

It has since become the most widely used vaccine in the world, with around 130 million children vaccinated each year
.

Interestingly, epidemiological studies shortly after the introduction of the BCG vaccine in Europe in the 1920s found that it significantly reduced infant mortality, which cannot be explained solely by the reduction in tuberculosis cases
.

Later, similar studies in other regions, including randomized clinical trials, showed up to a 50% reduction in mortality due to infant BCG vaccination
.

Likewise, BCG, but not other childhood vaccinations, was associated with significantly higher early childhood survival in high-mortality regions of West Africa
.

In particular, BCG appears to reduce child mortality by protecting against unrelated infectious pathogens, especially respiratory infections and neonatal sepsis, which is supported by clinical studies
.

Recent studies have shown that BCG immunization provides significant protection against viral infection by inducing trained immunity
.

Along this line, the potential benefit of BCG vaccination against COVID-19 has been positively hypothesized
.

Health care workers vaccinated with BCG have reported lower rates of COVID-19 compared to unvaccinated employees
.

On the basis of these findings, trained immunity induced by the BCG vaccine may provide nonspecific protection against SARS-CoV-2 and reduce the severity of COVID-19 disease, a strategy that may lead to important public health benefit
.

In this study, the K18-hACE2 mouse model was used to assess whether BCG vaccination provides protection against SARS-CoV-2
.

This study demonstrates that intravenous BCG (BCG131 iv) vaccine induces a robust innate immune response, restricts SARS-CoV-2 replication, and improves SARS-CoV-2-induced weight loss in a K18-hACE2 mouse model
.

Overall, this study provides experimental evidence for a causal relationship between BCG-iv vaccination and protection from SARS-CoV-2 infection in vivo
.

Reference message: https://insight.
jci.
org/articles/view/157393