BCG vaccine helpful against neo-coronavirus?
Some recent studies suggest that the BCG vaccine, which people would have received in infancy, may be able to protect against the neo-coronavirus. If this is true, then it is certainly good news because BCG vaccine has been used for many years and the production process is mature enough to make it quickly. But the most relevant question is, can BCG really help us to protect against the new coronavirus?
From the current research, it seems that BCG vaccine may help to boost the overall immunity of the body, allowing the body to have a stronger immune response when it encounters a viral invasion. Then, BCG vaccine is expected to be put into use before the birth of a vaccine specifically for the neo-coronavirus, boosting people's resistance to the neo-coronavirus and reducing the pressure on the healthcare system. However, this is not the final word, and teams of researchers in the Netherlands and Germany are trying to give definitive answers through a series of clinical trials.
What is BCG vaccine?
When we talk about the history of human vaccine development, the birth of BCG vaccine is undoubtedly an important event to remember. For a long time, mankind had nothing to do with tuberculosis, a disease that has been associated with the history of human civilization and has claimed countless lives. It was not until 1882 that the German microbiologist Robert Koch discovered the causative agent of tuberculosis, Mycobacterium tuberculosis, and in 1907, two French microbiologists, Albert Calmette and Camille Guérin, inspired by cowpox, chose a strain of Mycobacterium tuberculosis of the bovine type and began a long and far-reaching experiment. After 13 years and 231 generations of culture, they obtained a strain that was much less pathogenic and did not cause disease, but which still triggered an immune response in the human body to Mycobacterium tuberculosis. And it was from this strain that the BCG vaccine was made.
The BCG vaccine completed human trials in 1921 and was subsequently promoted and began to be widely used for tuberculosis prevention. Today, as the only vaccine against tuberculosis, BCG is one of the most frequently administered vaccines in human history. Although the effectiveness of BCG has been somewhat questioned in recent decades, BCG is still given to newborns in many countries, including China, according to the recommendations of the World Health Organization (WHO).
What Calmette and Guérin must not have expected when they invented BCG, however, is that 100 years later, scientists have higher expectations for BCG - several clinical trials on BCG are underway or about to be conducted in countries such as the Netherlands, the United Kingdom, and Germany. This time, though, the purpose of these trials is to test whether BCG can improve human resistance to the new coronavirus.
Why are these scientists pinning their hopes of fighting the new coronavirus disease on this vaccine designed for tuberculosis? It starts with the mechanism of action of the vaccine.
How does the vaccine work as an immune agent?
We know that when pathogens, whether bacteria or viruses, enter the body, the immune system organizes two lines of defense against foreign enemies: the natural immune system (nonspecific immunity) and the adaptive immune system (specific immunity). The first line of defense is the innate natural immune system, in which the immune cells involved include phagocytes and natural killer cells. They are activated when they encounter pathogens and thus clear them.
When the natural immune system is not effective, the body needs a second line of defense, the adaptive immune system, to fight the pathogens. Adaptive immune system T cells and B cells are such lymphocytes. When they fight a pathogen, they make a memory, "remembering" what the pathogen looks like. Thus, the next time a similar pathogen invades, the T cells and B cells that have acquired the "memory" can respond quickly and effectively kill the pathogen.
Vaccines are designed to mimic disease-causing pathogens, either as attenuated or inactivated viruses (i.e., modified viruses that do not cause disease, as in the case of BCG), or as fragments or shells of viruses. Their role is to train T cells and B cells to develop a memory for a specific pathogen, allowing the body to gain resistance against the pathogen.
The BCG vaccine prevents TB by the same mechanism. As a live attenuated vaccine with attenuated toxicity, it allows the body to produce antibodies specific for the TB pathogen, Mycobacterium tuberculosis, which creates immunity to TB.
With that said, you should have noticed - Mycobacterium tuberculosis and coronavirus are not related, so why do some scientists believe that BCG has the potential to ward off coronavirus disease?
Why does the BCG vaccine have the potential to protect against the new coronavirus?
As mentioned earlier, after vaccination, T and B cells in the adaptive immune system can gain memory. What about the cells in the natural immune system? Because of the lack of memory capacity, the scientific community generally believes that vaccines cannot make such immune cells develop memories as well.
Recently, however, some studies have proposed a different view. Previous tests in mice showed that BCG reduced the chance of respiratory infection in mice and that mice previously vaccinated with BCG had fewer symptoms and lower concentrations of the virus in their blood after exposure to influenza A virus. In other words, BCG vaccine can prevent viral infection to some extent, and even if infected, it is expected to reduce symptoms.
Evidence in humans is also emerging, and in 2016, the journal Science published a review article discussing the role of several vaccines, including BCG, in boosting natural immunity. This article concluded that the active ingredient in the BCG or measles vaccine survives in the body for several months after vaccination. In this way, the vaccine stimulates the natural immune system for a long time while prompting the production of memory in T and B cells, thus boosting the overall immunity of the body and reducing the risk of the body being infected by pathogens for months or even more than a year after vaccination. Mihai Netea, an epidemiologist at Radboud University in the Netherlands, refers to this immune response as "trained immunity".
Although many details of the molecular mechanism of "trained immunity" remain uncertain, the paper provides a general explanation: BCG and measles vaccines alter the epigenetic characteristics of natural immune cells such as granulocytes, macrophages, and natural killer cells (i.e., they do not alter the DNA sequence of these cells. but certain chemical groups on the DNA are altered, and this alteration is heritable). And such an alteration causes a series of other changes that allow the natural immune system to produce a stronger response when a pathogen invades the body.
If this conclusion holds true, then this would mean that BCG vaccine prevents TB while also enhancing the overall immunity of the vaccinated person and reducing the likelihood of contracting other viruses.
The effectiveness of BCG vaccine remains to be clinically proven
As the New Crown epidemic continues to spread, Netea is collaborating with research institutions in different countries to study the relationship between BCG and the natural immune system, in the hope that BCG can play a role in preventing the epidemic while a vaccine for New Crown is still being developed. Recently, Netea announced that it will collaborate with researchers at Utrecht University in the Netherlands to conduct clinical studies.
Slightly unfortunately, however, although the researchers hope to find a clear relationship between BCG vaccine and neo-coronavirus disease, their trial is still limited by funding and operational difficulties to test whether the vaccine can boost the overall immunity of the human body. In addition, research teams in the United Kingdom and Australia will each conduct similar trials in their own countries.
Almost simultaneously, another trial is set to begin in Germany, and it is even more targeted. 2017, scientists at the German Max Planck Institute for Infection Biology developed a vaccine called VPM1002 based on the BCG vaccine. Compared to the regular BCG vaccine, VPM1002 enhances the immune system's ability to recognize antigens.
The team has previously demonstrated in clinical trials that VPM1002 can be used to treat bladder cancer and prevent recurrence of bladder cancer. Now, the designers of VPM1002 will begin testing the effectiveness of VPM1002 against novel coronaviruses. In the researchers' opinion, they do not expect VPM1002 to actually work as a vaccine for the new coronavirus, but VPM1002 is advantageous in that it is immediately available and, if it passes clinical trials, could boost people's immunity with VPM1002 in the present, thus reducing the pressure on the healthcare system.
Finally, it is important to note that whether BCG actually helps against the neo-coronavirus is yet to be clinically proven, and based on the available evidence, the protective effect of BCG in adults is quite limited. Maintaining good hygiene practices is an effective strategy to avoid contracting diseases such as the New Coronavirus.
