Can BCG help protect against the new coronavirus? Multiple teams are jointly verifying

Some recent studies have shown that the BCG vaccine, which people are vaccinated with in infancy, may be able to protect against the new coronavirus. If this is true, it is undoubtedly good news, because BCG has been used for many years and the production process is mature and can be manufactured quickly. But the most important question is, can BCG really help us protect against the new coronavirus?

According to current research, BCG may help improve the body's overall immunity and produce a stronger immune response when the body encounters a virus invasion. Then, BCG is expected to be put into use before the birth of a vaccine specifically for the new coronavirus, to improve people's resistance to the new coronavirus and reduce the pressure on the medical system. However, this is not the final conclusion. Research teams in the Netherlands and Germany are trying to give a definite answer through a series of clinical trials.

What is BCG vaccine?

When we talk about the history of human vaccine development, the birth of BCG is undoubtedly an important event worth remembering. For a long time, humans were helpless against tuberculosis, which has accompanied the history of human civilization and claimed countless lives. It was not until 1882 that German microbiologist Robert Koch discovered the pathogen of tuberculosis, Mycobacterium tuberculosis. In 1907, two French microbiologists, Albert Calmette and Camille Guérin, were inspired by cowpox and chose a strain of bovine Mycobacterium tuberculosis to start a long and far-reaching experiment. After 13 years and a total of 231 generations of cultivation, they obtained a strain with much lower pathogenicity and no disease, but this strain can still induce an immune response in the human body, making the human body immune to Mycobacterium tuberculosis. And BCG is made of this strain.

In 1921, BCG completed human trials and was subsequently promoted and widely used to prevent tuberculosis. Today, as the only vaccine to prevent tuberculosis, BCG has become one of the most frequently administered vaccines in human history. Although the effectiveness of BCG has been questioned in recent decades, many countries, including China, still vaccinate newborns with BCG according to the recommendations of the World Health Organization (WHO).

However, when Calmette and Guérin invented BCG, they certainly did not expect that 100 years later, scientists would have higher expectations for BCG. In countries such as the Netherlands, the United Kingdom, and Germany, a number of clinical trials on BCG are being or will be carried out soon. However, this time, the purpose of these trials is to test whether BCG can improve human resistance to the new coronavirus.

Why do these scientists place their hopes for preventing and treating COVID-19 on this vaccine designed for tuberculosis? This starts with the mechanism of action of the vaccine.

How do vaccines work?

Image source: pixabay

We know that no matter it is bacteria or virus, when pathogens enter the human body, the immune system will organize two lines of defense to resist foreign enemies, namely the innate immune system (non-specific immunity) and the adaptive immune system (specific immunity). The first line of defense is the innate innate immune system, in which immune cells including phagocytes and natural killer cells are involved. When they encounter pathogens, they are activated and eliminate the pathogens.

When the natural immune system fails to work, the body needs a second line of defense - the adaptive immune system to fight pathogens. Lymphocytes such as T cells and B cells of the adaptive immune system. When they fight pathogens, they will leave memories and "remember" the appearance of the pathogens. In this way, the next time a similar pathogen invades, the T cells and B cells that have acquired "memory" can respond quickly and effectively kill the pathogens.

Vaccines simulate pathogens that cause disease. They may be attenuated or inactivated viruses (that is, modified viruses that do not cause disease, like BCG), or fragments or shells of viruses. Their role is to train T cells and B cells to form a memory of specific pathogens, allowing the body to gain resistance to pathogens.

The same is true for the mechanism of BCG in preventing tuberculosis. As a live attenuated vaccine with reduced toxicity, it can enable the body to produce specific antibodies against the tuberculosis pathogen, Mycobacterium tuberculosis, thereby producing immunity to tuberculosis.

At this point, you should have noticed that Mycobacterium tuberculosis and coronavirus are not related at all, so why do some scientists believe that BCG has the potential to protect against coronavirus disease?

Why is BCG likely to protect against the new coronavirus?

Figure caption: Coronavirus under a microscope, Image source: Wikipedia

As mentioned above, after vaccination, T cells and B cells in the adaptive immune system can acquire memory. What about cells in the innate immune system? Due to their lack of memory ability, the scientific community generally believes that vaccines cannot make these immune cells develop memory.

But recently, some studies have put forward different views. Previous mouse experiments have shown that BCG can reduce the chance of respiratory virus infection in mice, and after exposure to influenza A virus, mice that have been vaccinated with BCG have milder symptoms and lower virus concentrations in their blood. In other words, BCG can prevent viral infection to a certain extent, and even if infected, it is expected to alleviate symptoms.

Evidence in the human body has also emerged. In 2016, Science magazine published a review article discussing the role of multiple vaccines, including BCG, in enhancing natural immunity. The article believes that after vaccination with BCG or measles vaccine, the active ingredients in the vaccine can survive in the body for several months. In this way, while the vaccine prompts T cells and B cells to produce memory, it can also stimulate the natural immune system for a long time, thereby improving the body's overall immunity and reducing the risk of infection by pathogens for several months or even more than a year after vaccination. Mihai Netea, an epidemiologist at Radboud University in the Netherlands, calls this immune response "trained immunity."

Although many details of the molecular mechanism of "trained immunity" are still uncertain, this paper also gives a general explanation: BCG and measles vaccines can change the epigenetic characteristics of natural immune cells such as granulocytes, macrophages, and natural killer cells (that is, the DNA sequence of these cells has not been changed, but certain chemical groups on the DNA have changed, and this change is heritable). Such changes cause a series of other changes, allowing the natural immune system to produce a stronger response when pathogens invade the human body.

If this conclusion is true, it means that while BCG can prevent tuberculosis, it can also enhance the overall immunity of the vaccine recipient and reduce the possibility of infection with other viruses.

Whether BCG is effective still needs clinical verification

As the COVID-19 pandemic continues to spread, Netea is working with research institutions in different countries to study the relationship between BCG and the natural immune system, hoping that BCG can play a role in preventing the pandemic when the COVID-19 vaccine has not yet been developed. Recently, Netea announced that it will work with researchers at Utrecht University in the Netherlands to conduct clinical research. Unfortunately, although researchers hope to find a clear relationship between BCG and COVID-19, their trials are still limited by funding and operational difficulties to test whether the vaccine can enhance the body's overall immune capacity. In addition, research teams in the United Kingdom and Australia will also conduct similar trials in their own countries.

Almost at the same time, another trial will be launched in Germany, which is more targeted. In 2017, scientists from the Max Planck Institute for Infection Biology in Germany developed a vaccine called VPM1002 based on BCG. Compared with ordinary BCG, VPM1002 can enhance the immune system's ability to recognize antigens.

Previously, the research team has confirmed in clinical trials that VPM1002 can be used to treat bladder cancer and prevent the recurrence of bladder cancer. Now, the designers of VPM1002 will begin to test the effectiveness of VPM1002 in resisting the new coronavirus. In the view of the researchers, they do not expect VPM1002 to be a real vaccine for the new coronavirus, but the advantage of VPM1002 is that it can be put into use immediately. If it can pass clinical trials, it can enhance people's immunity through VPM1002 at the moment, thereby reducing the pressure on the medical system.

Finally, it should be pointed out that whether BCG really helps to resist the new coronavirus has yet to be clinically verified, and based on existing evidence, the protective effect of BCG on adults is quite limited. To avoid infection with diseases such as the new coronavirus, maintaining good hygiene habits is the most effective strategy.

Author | Wu Fei

Reviewer | Zhang Wentao, PhD in Virology, Wuhan University

This article was published by Tencent Science Popularization "Everyone Loves Science" team

Please indicate that the source of the reprint is from Science Popularization China

References:

https://www.sciencemag.org/news/2020/03/can-century-old-tb-vaccine-steel-immune-system-against-new-coronavirus#

https://science.sciencemag.org/content/352/6284/aaf1098

https://www.mpg.de/14610776/immune-boost-corona-virus

https://microbewiki.kenyon.edu/index.php/Bacillus_Calmette-Gu%C3%A9rin_therapy#Other_Uses_of_BCG