About influenza

 

I received an e-mail from a patient saying, "Does the new influenza vaccine fit this winter? How do you make it?"

I will tell you the basics of how to make a vaccine.


A vaccine is a virus. Viruses can only grow in living cells, so to make a vaccine, you need a lot of cells that can grow the virus that will be the vaccine.

It has long been known that influenza seems to be a viral illness. This is because it was possible to develop a cold by collecting the runny nose of a patient with a cold, putting it through a filter that does not allow bacteria to pass through, and dropping the runny nose from which the bacteria have been removed into the human nose.

However, it was difficult to find a way to propagate the causative virus in animals other than humans. The first animal to be found to propagate the human influenza virus was the Mustelidae ferret. However, since ferrets are carnivorous animals and have an odor peculiar to Mustelidae, they have the drawback of being difficult to use in experiments.

Next, we found a special young cell called a developing chicken egg. Chicken eggs, which are the host for transmitting viruses, have various characteristics and are still used worldwide for vaccine production.

Influenza has a changing virus every year, so it is difficult to predict what kind of virus should be used as a seed for the vaccine to be used next winter even one year before the epidemic occurs. It's a difficult problem. This is because if the type of virus that is prevalent and that of the vaccine are different, the vaccine will not be very effective.


In Japan, the National Institute of Infectious Diseases is responsible for the selection of vaccine seed viruses.

Next winter, for example, if we scientifically determine that H3N2 or H5N1 will be prevalent, we will distribute the virus to vaccine manufacturers nationwide. Once the seed virus for the vaccine has been determined, each vaccine manufacturer is ready to make it.

First of all, we will arrange chicken eggs. Ultimately, to make a vaccine for millions of people, each manufacturer uses about one million chicken eggs every day.

The expression chicken egg is a bit scientifically inaccurate and is formally called a developing chicken egg. If the fertilized egg is kept warm in a furan device at about 37 ° C, chicks will be born 21 days later. The period until the chick is born, that is, the state in which the chick's body is being made, or in other words, the state in which it is developing until it hatches, is called a developed chicken egg. Chickes are born in 2 days, but 10 to 12 day old developed chicken eggs are used for the growth of influenza virus. Eggs grown during this period have a collar called eggshell on the outside, thick blood vessels run just inside the collar, and a white membrane called eggshell membrane is formed, and oxygen is exchanged between this shell and eggshell membrane. Chicken embryos, which are nutrients for yolks and whites and are equivalent to mammalian fetuses, are growing day by day. Chicken embryos float in amniotic fluid in a transparent, thin membrane called the amniotic membrane. The cells that form a large bag surrounded by the allantois are the place of virus growth, and the propagated virus appears in the urinary fluid. Move the heat-retained chicken egg to a dark room, shine light from the outside of the eggshell to confirm that the chicken embryo is moving well, inject the influenza virus directly from the outside of the eggshell, return it to the incubator, and keep it warm for about 3 days. increase. In the meantime, make sure the chicken embryos are healthy and discard the dead eggs.

Next, tests are conducted to confirm safety and efficacy.

One of them is the sterility test. In addition, a fever test will be conducted to see if it causes fever by injecting it into rabbits, and if it is injected into guinea pigs to see if it causes weight loss. Make sure that this virus solution is injected into the animal to produce enough immune antibodies.

Finally, the virus concentration is adjusted using a special method so that only the virus solution that is sterile by self-test and confirmed to be harmless by animal tests is given strong immunity when injected into humans.

After that, it will be sent to the National Institute of Health of the Ministry of Health and Welfare for national certification.

A national certificate is attached to each lot that has passed, and the vaccine as a medicine is finally completed.


Vaccine making is a daunting task that takes a lot of time and effort, requires great care to be sterile throughout the process, and takes several months to complete the process.

Vaccines are made by each research institute on their own at the request of the state.


Previously, the number of people vaccinated against influenza was 0.3% of the population, which is an unprecedented number in the world. As a result, tens of thousands of elderly people are victims of the flu each year. It is absolutely impossible to get a vaccine and say, "There is a lot of harm and no benefit." There is no cure for viral illnesses, so vaccine prevention, if not perfect, is the best defense.


Difference between vaccine and serum

I received an email saying, "I use a vaccine to cure a disease, and I use serum when I am bitten by a venomous snake. Is there serum for influenza?"

The general public may not know the difference between vaccines and serum, so I will explain by answering the questions.


If you are bitten by a venomous snake that has a deadly poison like a pit viper, or if you are infected with a deadly poisonous bacterium like Clostridium tetani, you can die if you leave it alone. Snake venom dissolves cells, and Clostridium tetani venom paralyzes nerves. For such poisonous disasters, when a serum containing an immune antibody against the poison (anti-toxin immune serum) is injected, the antibody against the poison binds to the poison and eliminates the poisonous power (scientifically neutralized).

The treatment of diseases with immune antibodies is called immunoserum therapy, which was discovered by Dr. Shibasaburo Kitasato for the first time in the world, and the immune serum against snake venom is an excellent one studied by Dr. Taichi Kitasato, a disciple of Dr. Shibasaburo Kitasato.

Serum therapy is a treatment based on immunological theory. Vaccines are also used to prevent and treat diseases caused by immune antibodies. Both vaccines and immune sera basically use immune antibodies, but what's the difference? First of all, I will explain the types of immunity.


It has long been said that once you get measles, you never get measles again. this is true. Measles is a disease caused by the measles virus, which propagates in the body and travels throughout the body in the flow of blood. In other words, the measles virus stimulates cells throughout the body that make immunity, resulting in a strong biological defense mechanism. This function of protecting the living body is called immunity. Immunity means making a substance called an antibody that is induced by a foreign substance that has invaded the body, such as measles virus, and binds only to measles virus. Substances that make antibodies, such as measles virus, are called antigens. A substance that is produced by an antigen and has the property of binding only to the antigen is called an antibody. Even if the measles virus, which is an antigen, invades the living body and causes illness, antibodies can be produced in the body. If the antibody is present in the blood, even if the measles virus invades again, the antibody that was present before the infection can immediately catch and neutralize the virus. In nature, only humans can get measles. So suppose you inject a lot of measles virus into a rabbit many times. The rabbit is not infected with measles virus and does not become measles, but the body has antibodies against measles virus. After all, regardless of whether or not you get sick, when an antigen enters the body, an antibody is produced.

The process of being infected and producing antibodies to immunize is called "active immunization". If you inject the antigen many times, an antibody will be formed in the blood, and even if you inject the blood containing the antibody into another person, the antibody can be present in the blood.

Transferring blood or serum containing antibodies to another individual for immunization is called "passive immunity". In the "active immunization" method in which a vaccine is injected to immunize, it takes more than a week for the body to produce an immune antibody by itself, but the produced immunity lasts for many years. increase.

On the other hand, in the "passive immunity" method, in which serum containing an antibody is injected to immunize, the antibody is transferred and temporarily immunized, so that the antibody is not produced and the immune state is immediate. , Antibodies are not made, so long-term sustainability cannot be expected. It is possible to make sera containing immune antibodies against the influenza virus.

However, since it is unknown when the virus will be infected, it is not possible in principle to inject immune serum in advance to prepare for the infection because of the persistence of the antibody in the body.

Antiserum therapy is an epoch-making treatment method established by Dr. Shibasaburo Kitasato 100 years ago.

For tetanus and venomous snakes, injection of immune serum has immediate effects.

But there are also problems. For example, a human is bitten by a pit viper and is given a horse serum containing an antibody made by immunizing a horse. For that human, horse serum is a foreign substance, so antibodies can be produced. Suppose that same person now has tetanus, which requires serum injection, but can only be used with immune serum made from animals other than horses. The reason is simple: injecting horse serum into a person who has horse antibodies will cause shock and die from respiratory distress. Therefore, in order to overcome this shortcoming, serum therapy would be perfect if human antibodies could be produced without using antibodies from different animals such as horses and sheep.

However, humans cannot be experimental animals for whatever reason or need.

Amazingly, Dr. Shibasaburo Kitasato predicts that immune antibodies will be made with biotechnology in the future in the next few years without using animals. The problem can be solved by using the advanced technology of biotechnology. Since human antibody molecules are made by human lymphocytes, technological innovations that enable human lymphocytes to proliferate in vitro are awaited.

In the Meiji era, there were a lot of extremely talented human resources.

It seems that the Japanese are not without creativity. There may be nothing in education today that leads to creativity.

Don't you think so too?

It is also written in Ryotaro Shiba's "To You Who Live in the 21st Century".

The letters are large and can be read by small children.

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