Vaccines: A review of their structure and function
“The COVID-19 vaccine” - the silver bullet we were all eagerly waiting for and perhaps the phrase in which we hear the term “vaccine” most frequently these days. With all the discussions buzzing around, ranging from scientific, to political debates about this, let us take a quick look at what vaccines are, how they work, and their importance in our lives.
The commonly prevalent methods to control the spread of an infectious disease can be classified into two broad categories - prevention and treatment.
There are two common ways to prevent the spread of disease. First, by avoiding contact with infectious agents, and second, by preventing the further spread of the agent from individual to individual. Effective prevention of a disease depends primarily on the understanding of the transmission dynamics of the particular infectious agent. The other control effort, i.e., treatment, refers to treating the infected population and thereby stopping the further spread of the disease.
Vaccines prepare our body for fighting against disease-causing agents and thus the effective prevention of a particular disease relies on vaccines. Vaccines are defined as a substance used to stimulate the production of antibodies - the ammunition in our bodies to fight diseases These antibodies provide immunity against one or several diseases. Vaccines are prepared from the causative agent(s) of the disease, its products, or a synthetic substitute, treated to act as an antigen (identified by our body as a disease-causing trigger) without inducing the disease.
Discovery of vaccines
The discovery of vaccines goes back to the 18th century when smallpox was raging havoc through human societies like a wildfire. Smallpox was caused by two closely related virus strains - Variola major, which was very virulent and had a 30% mortality rate, and Variola minor, which was less virulent with a 1% mortality rate. Eventually, science was triumphant in eradicating the smallpox virus. In fact, smallpox was the first and the only human disease to be eradicated by vaccines.
Now, it is ironic that medicinal science asks to intentionally infect a person in order to prevent disease, and that in fact, is the very backbone of the process of vaccination.
It is believed that this process of infecting an individual with small amounts of the virulent or disease-causing agent, originated from India or China. It was first introduced to the western world in 1721 by Lady Mary Montagu, in England. This process involved deliberate administration of the smallpox virus in small amounts to uninfected individuals so that they develop a mild but protective infection. This small amount of infection, which was not enough to cause the disease but enough to initiate the process of antibody production within the bodies of these individuals, now armed them to fight further and a serious dose of infection.
There were three serious drawbacks in this process of variolation. Firstly, it did not always stimulate immunity (antibody production). Secondly, it sometimes caused smallpox and resulted in the patient's death. Thirdly, it could set off a transmission chain and cause collateral cases in other susceptible individuals. However, with the progress of science, such drawbacks were minimized, and the methods of vaccination matured. Nonetheless, variolation still remains an active area of research and continues to remain the vaccination method for some diseases.
How did the smallpox vaccine come into being?
When the smallpox virus was around, it was a common observation that milkmaids were mostly immune to the virus. Edward Jenner, now referred to as the father of Immunology noted that cowpox, a virus naturally circulating in wild rodents and infecting cows, caused a mild infection in humans, thus generating an immune response in those humans, against similar viruses. To test this theory, Jenner infected (inoculated) his gardener's son with cowpox blisters from a milkmaid. He and 23 other infected individuals were exposed to variola. It was observed that they were all immune to variolation. The Latin word for cow is "Vacca," and hence Jenner initially named the method "vaccinus," which means "from cows."
How do vaccines work?
Our body has its own immune system, composed of a type of cells called the white blood cells. Among the different types of white blood cells are three primary kinds called the macrophages, B-lymphocytes and T-lymphocytes. B-lymphocytes produce antibodies - a type of protein that binds itself to the disease-causing agent or foreign particle (antigen) that has entered the body. Macrophages are responsible for engulfing this antibody-antigen complex that is formed. T-lymphocytes have a certain memory and can remember these antigens or foreign particles and thus remain ready to re-initiate this process whenever the body is again attacked by those foreign particles.
Now, vaccines contain live or inactivated infectious agents (foreign particles/antigens) that mimic an infection, thus causing the immune system to initiate this process. Once this simulated infection subsides, the body is left with memory T-lymphocytes as well as B-lymphocytes that will produce an immune response if the body comes in contact with the same infectious agent in the future.
Types of vaccines
Although the common knowledge is that vaccines are either live or inactivated forms of infectious agents, this is often an oversimplification. A more detailed classification of vaccines is as follows:
Live (attenuated)vaccines: These vaccines contain the live but much-weakened version of the infectious agent so that they mimic the infection and yet do not cause a severe infection, all the while stimulating our immune system. Examples include vaccines against Measles, Mumps, Rubella (MMR), and chickenpox.
Inactivated vaccines: These vaccines are made up of dead infectious agents that can stimulate an immune response. Often multiple doses of this vaccine are required to maintain the required immune function. A classic example of such kinds of vaccines is the oral polio vaccine.
Subunit vaccines: These vaccines include a part of the infectious agent instead of the live or the inactivated form of the entire germ. This part is usually the component of the antigen which is responsible for triggering the immune response. Subunit vaccines are known to have the least side effects. An example of this type is the pertussis component of the DTaP (Diptheria, tetanus, Pertussis which causes whooping cough) vaccine. This vaccine is also a conjugate vaccine.
Conjugate vaccine: Conjugate vaccines are the ones developed to specifically target the antigens that have a complex sugar coating around them. This coating helps the antigens to disguise as other biological molecules. This makes it harder for an underdeveloped immune system (for example in children) to recognize the antigen and respond accordingly. However, conjugate vaccines are prepared such that they can recognise the coating as well as the actual antigen covered by it, and thus helps the immune system to act. The vaccine against pneumonia is an example of such a vaccine.
Effectiveness of vaccines
The evaluation of the effectiveness of a vaccine depends critically on keeping track of the number of people who have been prevented from contracting a disease because of vaccination. As one might imagine, this is a complicated business. Such complications can arise due to numerous reasons. For example, some doses of vaccines fail to stimulate immunity. Also, often infants who still have their mother's immunity passed on to them, do not develop their own immune protection despite being vaccinated. Moreover, vaccinating an individual also might prevent the transmission of the disease to people who might be infected.
To give you a perspective of the effectiveness of vaccination programs in the past, it is noteworthy to mention that the childhood mortality rate due to measles has gone down by 74%. Also, the number of individuals affected by measles around the world has gone down by 62%. It has also been estimated that nearly 700,000 deaths have been averted due to vaccination for Haemophilus influenzae type B and 3.8 million future deaths have been averted due to vaccination for Hepatitis B.
To estimate the actual impact of vaccination, we need to consider both its direct and indirect effects. Vaccination of infants, for example, can lead to a long-term effect on a population with respect to the particular disease that the vaccine targets. If P is the probability of successfully vaccinating an infant, P can also be described as P = (proportion of infants vaccinated) x (vaccine efficacy). Let us suppose, an infection removes susceptible individuals at a rate related to the basic reproductive number (the average number of secondary infections produced by a typical case of an infection in a population where everyone is susceptible), RO. Also, the number of new births adds to the number of susceptibles in the population. Therefore, the susceptibles reduce in number when we immunize a proportion P, of the new births. Thus the effective reproductive rate Reffective, for an infection, in a population, where P percent of individuals have been immunized, is, (1-P) RO. If Reffective is the expected number of new infections due to a single infection, when Reffective is greater than one, an epidemic is said to have broken out. The critical immunization fraction needed so that P is less than 1, i.e. an epidemic doesn't break out is, therefore, P>(1- 1/RO). This fairly simple infection model suggests that we can effectively prevent an infection from swooping across an entire population by immunizing less than 100% of the newborns. This is what is commonly known as herd immunity.
From the model discussed above, we can see immediately that as the reproductive number(RO) increases, the proportion of children born that would need to be vaccinated also increases. Thus the RO value for a population determines what proportion of children need to be vaccinated to prevent a particular disease. For instance, for a pathogen like smallpox, with RO of approximately 5, we might only need to immunize 80% of the newborn children, whereas, for pathogens like mumps or chickenpox, with RO nearer to 10, about 90% of the children would need to be vaccinated. It should be noted here, that the herd immunity threshold is the percentage of the population that must be immunized, and not just vaccinated. Generally, pediatric vaccination, with pertussis or measles vaccine, stimulates immunity in less than 90% of infants due to its interactions with maternal immunity still present in the infants. So, infant-based vaccination strategies alone are often not enough to be effective in achieving the eradication of pathogens, with a high transmissibility. While herd immunity can be an effective strategy, indicating that eradication of a disease may be possible, it also comes with its inherent limitations and challenges for implementation.
Like any other medication, vaccines can also sometimes lead to health risks in the form of side effects. An example of such skepticism arose due to the usage of thimerosal (a mercury-containing compound) in vaccine preservatives. It was found that this component might be linked to many autism cases. After proper investigation, the use of thimerosal was banned. These instances led people to be wary of vaccination drives. These strong beliefs are an important contributor to the drop in vaccination rates. But on the other hand one should remember, it is because of the proven high effectiveness of the vaccines that the prevalence of some diseases in our society has rarified.
Alternatively, it would not be wrong to say that this has also created a false sense of safety where people believe that they or their children don't need to get vaccinated anymore because the disease is so rare anyway. But ironically, they fail to realize that in fact, the disease is rare because people get vaccinated, and if people stop getting vaccinated, the disease would become much more prevalent again.
Among other challenges in implementing a successful vaccination drive are the inability of some people to get vaccinated due to pre-existing medical conditions or even allergies to certain vaccines and their components.
Needless to say, clusters of unvaccinated people are at a high risk of causing a local disease outbreak. Even when the proportion of vaccinated people is high, the clustering of unvaccinated people can cause an outbreak because it can lead to long chains of transmission of the disease with an exponential growth characteristic. So as much as it is important to keep the vaccination engine warm, it should also be emphasised that large clustering of unvaccinated people should be avoided, to win the battle between Man and the Virus.
Srujana Mohanty is a third-year undergraduate student pursuing Integrated BS-MS in Chemistry, at IISER Kolkata. Besides writing, she enjoys coloring, singing, cooking, and watching series in her leisure time. She is also a cat lover.
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