In recent years, there has been increasing interest in protection from viral infections due to the COVID-19 pandemic. However, humans have an innate mechanism for defending themselves against various viral attacks (i.e., immune responses). This article will explain the general aspects of immune responses to viruses.
Viruses cannot reproduce on their own. To do this, they need to invade human cells and use their machinery to replicate. This viral replication process occurs when the human body is infected with a virus. An immune response will then be triggered during the very early phase of infection, which identifies virus-infected cells and removes viruses together with these cells. This mechanism is called "innate immunity." Generally speaking, an innate immune response is initiated within a few hours after infection. However, this response is not antigen-specific and might damage normal cells as well as infected cells. For example, when we are infected with a virus (i.e., catch a cold), we develop a fever. This is because an innate immune response causes our body temperature to increase, which impedes the viral reproduction.
This is why a viral fever is an uncomfortable symptom but is critically essential for recovery. Even if the body temperature is controlled with the use of antipyretic drugs, it will consequently lengthen the duration of an illness because these drugs will not eliminate the viruses themselves (i.e., the actual cause of the illness).
The crucial point is that innate immunity serves as the first line of defense against invading viruses. However, it enables temporary but not permanent prevention of viral infections because it has no immune memory (which I will discuss later).
After innate immunity, "adaptive immunity" occurs to fight against viral infections effectively. It recognizes specific viral components, destroys specific virus-infected cells, and produces antibodies that inhibit viral proliferation by binding them to particular viruses. It takes about two weeks after the first infection for the body to make enough antibodies against a virus. Once antibodies are produced, the infection will end. Even after recovery from the infection, our immune system retains antibodies in the blood against the virus that prevent future infections. The amount of antibodies will gradually decrease over time after the infection; however, memory immune cells producing antibodies will be stored in our body for a long time. Therefore, if we are infected with the same virus again, memory immune cells rapidly multiply and produce antibodies. Thus, the second infection will be inhibited before it can spread throughout the whole body.
That is why we often say that people who have already had measles (measles virus), chickenpox (chickenpox virus), or rubella (rubella virus) are highly unlikely to catch the disease again. Even if you are unsure whether you had any of those diseases when you were young, it is possible to check for the existence of antibodies for each virus by taking a blood test. If you have enough antibodies to a particular virus, you will not become infected with the virus even when it is spreading around you. This mechanism is called "individual immunity." So, why do we get infected with influenza again and again? The reason is closely related to our body's mechanism of producing antibodies. Antibodies recognize only some parts of viral proteins. The location and extent of viruses recognized by antibodies may differ among individuals, even though they are infected with the same virus. Influenza viruses have diverse types and easily mutate through viral proliferation. If their viral proteins change through mutation, previously produced antibodies are unable to recognize them, and thus, cannot prevent infection.
Vaccination is one of the methods to control viral infections, leveraging the mechanism of adaptive immunity that recognizes invaded viruses, produces antibodies, and prevents future infections. For human vaccination, the part of viruses with little or no infectivity is used. The vaccine stimulates immune responses and immune cells that produce antibodies. However, such immune responses are weak because the vaccine's stimulation to immune cells is much weaker than the actual viral infection. Therefore, most vaccinations require two doses or more.
The purpose of vaccination is to protect individuals from infectious diseases after they have taken a vaccine shot. Meanwhile, it is also possible to prevent or reduce the spread of infection in society if the majority of people have antibodies as a result of infection or vaccination. This mechanism is called "herd immunity."
Let us consider an example of measles. Measles is caused by the measles virus that has strong infectivity. Its symptoms include a red rash and fever, and even worse, it may lead to complications such as pneumonia or encephalitis, which can be fatal. Until the early 2000s, measles epidemics occurred every year in Japan. However, after the government started recommending vaccination from around 2004, the number of infected people decreased. By 2006, two doses of the measles-rubella vaccine were introduced as routine childhood immunization.
Nevertheless, in 2007, we saw a measles outbreak again among people in their teens and 20s. As these generations were not covered by the government's routine immunization program, they were considered to have insufficient antibodies to fight infections, which led to the measles outbreak. In response to this epidemic situation, the government determined to provide a second dose of the measles vaccine for five years from 2008 targeting children in their first year of junior high school and those in their third year of senior high school. As a result, the number of young measles patients decreased considerably in 2009 and thereafter. Subsequently, the outbreak of measles subsided across Japan. By recommending vaccination and increasing the number of people with sufficient antibodies, the government achieved herd immunity and successfully controlled the measles epidemic. In 2015, the WHO Western Pacific Regional Office verified that Japan had achieved measles elimination.
Another example concerns rubella. A nationwide rubella epidemic occurred in Japan during 2012 and 2013, due to the peculiar nature of the rubella virus. Rubella, also known as "three-day measles" or "German measles," is an infectious disease caused by the rubella virus. Its symptoms are similar to that of measles, such as fever and red rash spreading to the whole body. These symptoms are typically mild, and an attack can pass unnoticed (i.e., asymptomatic infection). However, if a pregnant woman is infected with the rubella virus during early pregnancy, her developing baby will be at risk of congenital rubella syndrome (CRS). CRS typically includes hearing impairment, cataracts, congenital heart diseases, and developmental retardation in children.
To prevent CRS, the Japanese government started mass vaccination against rubella in 1977, targeting junior high school girls. After 1995, this mass vaccination was replaced with individual vaccinations for both young girls and boys. In addition, two doses of rubella vaccine were also included in the government's routine immunization program for young children.
Along with the transition of the national rubella immunization program, the antibody prevalence rate of women has been maintained at around 95% since the introduction of the rubella mass vaccination. In contrast, the antibody prevalence rate of men (in their 30s to 50s) who were outside the scope of the girls-only mass vaccination was around 80%.
During the rubella epidemic in 2012 and 2013, as mentioned above, the infected from these generations were mostly male. Furthermore, pregnant women in their 20s and 30s who did not have sufficient antibodies were infected from these male patients. As a result, there was a sudden increase in the number of newborn babies with CRS. When there are people without antibodies, the mechanism of herd immunity will not function properly and the spread of infection will occur.
It is difficult to determine to what extent the entire society needs to have antibody prevalence in order to achieve herd immunity. This depends on the level of virus infectivity, the nature and duration of antibodies, and so on. In the case of COVID-19, it is said that when 60% of the entire society have antibodies against the coronavirus, the spread of infection can be curtailed. However, some reports insist that the strength of antibodies produced after a COVID-19 infection deteriorated quickly, and the effect of such antibodies to prevent infection was not yet confirmed. Therefore, the viability of herd immunity strategies against COVID-19 is still uncertain. Consequently, we still need to keep track of future studies and findings.