I don’t think so many people have ever been so interested in a ‘vaccine’ in the history of mankind. There is a lot of information, and there is also a lot of wrong information. Science Times is serializing 15 episodes of ‘Vaccine Story’ that anyone can understand. We hope for a lot of interest from our readers.
The word ‘vaccine’ originally came from the Latin word ‘vacca’, meaning cow. Edward Jenner started using this term when developing a smallpox prevention drug, and after Louis Pasteur changed the word a bit and named it ‘Vaccine’, it became global. The interesting part is that the German spelling of Vaccine is Vakzin, which is pronounced ‘Wakzin’ in Japan, and there are still a few people in Korea who still call vaccines Vakzin. In other words, in a narrow sense, a vaccine means a live vaccine (attenuated vaccine) obtained from ‘cow’, and broadly includes all preventive drugs developed after that, including live vaccines and further dead vaccines (inactivated vaccines). In modern times, it seems that it is not too wrong to think of it as a drug that prevents marine diseases by acquiring acquired immunity through antigen-antibody reaction.
Prevention of disease is not impossible even with various methods not based on these antigen-antibody responses. It is not impossible in modern times to use therapeutic agents in advance to prevent diseases, to prevent diseases by increasing the body’s innate immunity, or to prevent diseases by correcting innate genes. Conversely, there are cases where a strong immune response is induced through a vaccine, and treatment of an incurable disease that has already occurred is expected.
In this case, there is a sense of ambiguity as to how far the name ‘vaccine’ should be applied. However, it is often viewed as one of the desirable aspects of the next-generation vaccine in that it actively treats and prevents diseases. In what diseases and in what form will the vaccines to appear in the future be used?
death rate 1stomach, Can cancer be prevented?
One of the first diseases to be addressed is ‘cancer’. According to the statistics on the cause of death in 2019, 158.2 deaths per 100,000 people in Korea were due to cancer, ranking first in the entire country. This is 2.6 times higher than the second place, heart disease (60.4 people). Compared to the third and fourth places, pneumonia (45.1 cases) and cerebrovascular disease (42.2 cases), they are 3.5 times and 3.7 times higher. It is self-evident that if cancer can be conquered through a vaccine, the lifespan and health of mankind will be greatly improved.
So, is it really possible to prevent cancer through vaccines, that is, prophylactic drugs? In fact, some cancer vaccines have already been developed and used. If the cause is a virus. A typical example is cervical cancer, which is caused by the human papillomavirus. In addition to cervical cancer, it can cause cancers of the male genitals or around the anus, tonsils, etc., and cancer prevention is actually possible because the virus itself can be prevented.
In fact, liver cancer is also partially preventable, but hepatitis B is caused by infection with a virus. The death rate of liver cancer is 20.7 per 100,000 people, which is the second most common cause of death due to carcinoma, and 61.1% of the causes are the development of hepatitis B. In other words, if you can prevent hepatitis B, you can also prevent liver cancer with a high probability. The hepatitis B vaccine is also a liver cancer vaccine.
In addition to these indirect methods, ‘therapeutic vaccines’ are being discussed as other cancer prevention methods. Cancer occurs when cells in our body mutate. There are not many cases where pathogens from outside enter and cause it, and there are countless causes such as exposure to external stimuli (carcinogens, ultraviolet rays, etc.) and aging. There are many difficult cases, and it is not easy to specify cases that can be prevented by traditional antigen-antibody reactions. Therefore, it is necessary to consider a method of treating cancer as soon as it occurs in cells, rather than a vaccine that responds directly to pathogens in the body.
Here, attention is paid to the so-called third-generation anticancer drugs, which are immunotherapy drugs. The innate immune system in our body also considers mutated cancer cells to be enemies, but cancer cells survive by tricking them. Scientists have found a way to eliminate cancer cells by preventing them from evading the immune system and increasing the activity of immune cells. It is a completely new concept of treatment that allows immune cells to effectively find and eliminate cancer cells. James Allison, a professor at MD Anderson Cancer Center in the United States, and Tasuku Honjo, an emeritus professor at Kyoto University in Japan, who made a great contribution to finding this method, were awarded the 2018 Nobel Prize in Physiology or Medicine.
Recently, there is a movement to use such immunotherapy as a vaccine, and since both treatment and prevention are possible, this is also sometimes called a ‘therapeutic vaccine’. Immunotherapy can be expected to have a preventive effect for more than 10 years against the same type of cancer because it makes the cancer cells remember the cancer cells once they are treated. Therefore, if the insignificant cancer cells that have not developed into tumors are removed in advance by administering them in advance, the role of a cancer prevention vaccine is expected to prevent the occurrence of cancer. Currently, it is difficult for non-patients to choose because of the huge price of chemotherapy, but if more cancers that can be treated and mass production become possible, various cancer treatment vaccines are expected to appear. Based on this principle, research on therapeutic vaccines to be applied to various fields such as ovarian cancer is also increasing.
Expected to conquer various incurable diseases with curable + preventable ‘therapeutic vaccine’
The concept of a ‘therapeutic vaccine’, which treats and prevents disease at the same time, is already being studied in several places. Acquired immunodeficiency syndrome (AIDS) research is also cited as a case of a therapeutic vaccine. In 2020, a research team at Utah University of Health in the US developed a new AIDS treatment candidate and proved its effectiveness through animal experiments using monkeys. Researchers play a role in preventing HIV, the virus that causes AIDS, from entering cells. These drugs are mainly made in the form of peptides (amino acid polymers, intermediate forms between amino acids and proteins). The research team made the peptide structure in the form of an inverted ‘D-peptide’ as if reflected in a mirror, so that the drug’s effect was maintained for a long time. This drug prevents the body’s proteolytic component from recognizing the peptide itself. As a result, it stays in the body for a long time and exhibits sufficient medicinal effect. In other words, if this drug goes through clinical trials and is put to practical use, it is possible not only to treat AIDS patients in the future, but also to expect prevention, that is, a vaccine effect.
There are also efforts to conversely treat diseases using antigen-antibody reactions, which are characteristic of modern vaccines. In other words, the idea is to give a vaccine administered to a healthy person to a person who has already developed the disease and try to treat it beyond prevention. Among the many types of vaccines, there are many analyzes that ‘DNA vaccine’ is a suitable form for such a therapeutic vaccine, so it is expected to receive new attention in the future. DNA vaccines have a long-term effect because they insert a part of the pathogen’s DNA into the cells of our body and thereby continuously produce antigens. In addition, since humoral and cellular immune responses are induced together, a strong immune response that can effectively remove pathogens can be expected. A virus vector vaccine with a similar principle is also attracting attention for the same reason.
A representative example of applying this principle is hepatitis C. There is no fully commercialized vaccine for hepatitis C yet, and researchers expect that if a vaccine is developed in the future, it will become a ‘therapeutic vaccine’ that can be treated. Hepatitis C virus (HCV), which is located in the liver, through a vaccine, obtains strong acquired immunity from other parts of the body, and through this, a strong T-cell immune response is induced to treat HCV itself. Although it has not yet been fully put to practical use, there are several places where a similar principle is being challenged. The development of treatment technologies using human immunity itself is expected to increase in the future, and accordingly, the distinction between vaccines and therapeutics also tends to be blurred.
Should the vaccine be given by injection?
Various cutting-edge vaccines are emerging one after another, but as for the method of administering the vaccine to our body, we still use a syringe or inhaler as when Jenner’s vaccinia method was developed. There is no big difference in terms of convenience, as both require the help of medical staff. Because of this, it is difficult to supply vaccines to developing countries where even medical staff cannot find them. Is there no easy way to take the vaccine like a pill?
The biggest problem is storage and distribution. Vaccines can’t be used if ‘injured’ because their basic ingredients are similar to those of food. Gene vaccines are vulnerable to temperature changes due to their nucleic acid structure, so they need to be managed below freezing. Recombinant vaccines, as well as traditional attenuated and inactivated vaccines, use protein particles as they are, so refrigeration is the basic condition for most.
Efforts to solve this problem have been increasing recently. The first thing to point out is the ‘dry vaccine’. Using freeze-drying technology, antigen particles are dried similar to ramen soup, and although the effect has not been confirmed yet, it can be used in various forms if only successful in development. It can be mixed with sterile fluid and given by injection, or it can be administered through the nasal passages. Similar to asthma medications, inhalation through an inhaler can also be considered. This allows the vaccine to be absorbed through the alveoli, and the vaccine can be administered alone. It is possible to make an oral drug if it can be absorbed in the intestine.
Currently, multinational pharmaceutical companies such as Janssen, Sweden’s Iconovo, and Ziccum are preparing to commercialize dry vaccine technology. It is difficult to apply to attenuated vaccines that require an antigen to be alive, or mRNA vaccines that require direct delivery of genetic material into cells, but inactivated vaccines and recombinant vaccines are likely to be sufficiently applicable. If we go one step further, we may be able to get a vaccine that anyone can eat without a complicated process. In theory, it is possible to grow ‘crops’ containing vaccine ingredients. It is commonly referred to as a ‘green vaccine’ by cultivating a plant that has been modified to produce the same protein as the antigen through genetic transformation, then harvesting the plant and making it into medicine.
Growing these plants and ingesting them as food can have a preventive effect, but it is difficult to apply in practice, because the antigens eaten by mouth must pass through the stomach acid, and it is difficult to control the medicinal effects or side effects because it is difficult to accurately measure the intake. . Therefore, it is expected to extract only the necessary ingredients from these plants and make them into pills and distribute them. Research is underway in the scientific community, believing that the development of an edible vaccine to prevent hepatitis B and LTV (a type of diarrheal disease) will be promising.
There is a saying that medicine is ‘the endless hide-and-seek game between disease and humans’. As humans develop vaccines and therapeutics one step closer to conquering diseases, bacteria and viruses escape through mutations, which means that it will eventually become an endless battle. However, if we think about our lives just a few decades ago, before modern medical care was established, mankind is clearly winning this game of hide and seek. Although not all diseases will disappear completely in the future, it is undoubtedly true that our lives are becoming more and more healthier and more pleasant due to vaccines.