Since the advent of vaccines, public health infrastructures have seen a massive turnover worldwide. Immunization today is the cornerstone of public health policy, especially pediatric care. In countries with high vaccine accessibility, many diseases that caused deaths in childhood have disappeared. According to the World Health Organization, the current immunization strategies save 2-3 million lives each year. They have reduced mortality in children below five from 93 deaths in 1990 to 39 deaths in 2018 per 1,000 births.

Yet, vaccines remain misunderstood by many, and the anti-vaccination movement is constantly rising. So, let us understand and crack the excellent vaccine with its immunological impacts.

One can argue that immunology has not contributed much to vaccine development. Today, a better understanding of protective immunity is needed to counter the challenges in targeting some pathogens. Furthermore, with knowledge of immunological challenges, immunologists can produce the next generation of immunogens.

From the science behind vaccines to their historical timeline and socio-economic factors relevant to their performance and prevalence, our review entails everything needed to understand the topic. Let us get started!

What are Vaccines?

Vaccines are biological preparations that confer active acquired immunity against infectious diseases. Vaccines consist of particles that resemble or are from the pathogens to achieve this desired response. Some are extracted from naturally occurring pathogens, while some are produced in a laboratory synthetically. The essential component for most vaccines is the protein antigen. They are responsible for triggering an immune response within the body by stimulating white blood cells for phagocytosis and antibody production.

In general, vaccines induce an immune response by employing agents that resemble the disease-causing microorganism. They might as well be parts of the microbe itself. Suspensions of weakened, killed, or fragmented microorganisms get used. They can also contain toxins, surface proteins, antibodies, or lymphocytes. These foreign body particles induce an immune response in the body. It leads to the formation of antibodies and memory cells. These two later come in handy when the actual microorganism invades your body.

Types of Vaccinations

There are several types of vaccines. Generally, we classify vaccines as either live or non-live. The latter is often referred to as inactivated. It helps distinguish vaccines containing attenuated strains of the relevant replicating pathogenic organism against those that only contain some pathogen components or killed whole organisms (Fig. 1). However, over the past few years, several forms of vaccines have been developed. From viral vectors to RNA and DNA vaccines: there is a lot more vaccine variety in the modern-day world.

The following is a table with data on types of vaccines and an infographic that sums up the information!

Table 1: Tabulated data regarding the types of vaccines with the relevant licensed names used in public vaccination programs. The years of introduction with their diseases.

The Science Behind Vaccines – Features of Vaccine-Induced Protection

Vaccines are biological preparations of components that resemble or weaken antigens. They trigger an immune body response upon injection. The white blood cell receptors bind to them and do not recognize them as a part of your body. They are intruders, and your white blood cells undergo clonal expansion and selection. There is a production of lymphocytes that produce antibodies for the agglutination of antigens. Then, phagocytes for phagocytosis get manufactured. The body also develops memory cells that recognize the relevant invading antigens, conferring immunity when an infection occurs. These preparations are weak enough to cause no severe repercussions. It is that simple!

Immune Memory

When confronted with an infectious agent, a person with a vaccine against that pathogen can mount a more efficient and accurate protective immune response. When the incubation is lengthy enough for a new immune response to establish, immunological memory is adequate for defense against pathogens. For instance, in HBV, which has an incubation period of 6 weeks to 6 months, an immunized person is shielded after immunization, even if exposed to the virus sometime after the vaccine shot. The waning of antibody levels varies on the recipient’s age (which is very quick in babies due to a shortage of bone marrow niches for B cell survival), the nature of the antigen, and the number of booster doses injected.

For instance, the virus-like particles used in the HPV vaccine stimulate immune reactions lasting decades, whereas pertussis vaccines induce a fairly-short immune response. The inactive measles vaccine causes shorter-lived immunity than the live attenuated measles vaccine.

As a result, infectious diseases emerge soon after pathogen acquisition memory response controls these infections. Sustained immunity for protection through immunization may be hard to achieve. One solution is to give booster doses of vaccine throughout childhood (as is done with diphtheria, tetanus, pertussis, and polio vaccines) to keep antibody levels above the defensive threshold.

Vaccines that provide life-long protection do not have booster doses as a regular practice in adult life. For most countries, these childhood doses can achieve high coverage. Infectious diseases have a high prevalence in young children: persisted boosting after two years is not recommended.

1.  Herd Immunity

Although most vaccine development has focused on the direct protection of individuals through vaccination, which is imperative for new vaccine licensure, it has become clear that herd immunity is an important additional component of vaccine-induced safety.

Vaccines indirectly protect everyone. Some people cannot receive vaccinations for various reasons.

Fortunately, if a large population is immunized, one can halt the pathogenic transmission. As a result, disease incidence may fall even further than previously thought.

A Brief History of Vaccines

1. The First Vaccination: Discovery, Invention, and Effect

Edward Jenner, a British physician, invented the first vaccine in 1796. It used the cowpox virus (vaccinia) to protect humans from smallpox, a related virus. Previously, Asian physicians used the basic concept of immunization to protect children against smallpox by giving them dried shells from the disease’s lesions. Although some people developed immunity, others became infected with the disease.

Jenner’s contribution provided immunity through the substance related to but more secure than smallpox. He benefited from the uncommon circumstance where one viral infection confers immunity against another. In 1881, a French microbiologist named Louis Pasteur demonstrated anthrax immunization by injecting sheep with a formulation containing attenuated forms of the pathogenic bacillus. Four years later, he developed a rabies-protective suspension.

2. General Peek into History

Vaccination has been here for hundreds of years. In 17th century China, Buddhist monks drank snake venom to gain immunity to snake bites, and variolation existed (smearing a skin tear with cowpox to gain immunity to smallpox). In 1796, Edward Jenner found a vaccine. He is the founder of vaccinology in the West. He inoculated a 13-year-old boy with the vaccinia virus (cowpox) and demonstrated immunity to smallpox. The first smallpox vaccine came in 1798. The systematic implementation of mass smallpox immunization in the 18th and 19th centuries culminated in its global eradication in 1979.

Louis Pasteur’s experiments paved the way for human vaccines against live attenuated cholera and inactivated anthrax (1897 and 1904, respectively). In the late 1800s, a plague vaccine got developed. Bacterial vaccine development exploded between 1890 and 1950, including the Bacillus Calmette-Guerin (BCG) vaccination, which is still in use today.

Alexander Glenny perfected the use of formaldehyde to inactivate tetanus toxin in 1923. In 1926, the same method got employed to develop a diphtheria vaccine. Pertussis vaccine development took much longer, with the first whole-cell vaccine licensed for the United States in 1948.

From 1950 to 1985, viral tissue culture methods advanced, resulting in the development of the Salk (inactivated) polio vaccine and the Sabin (live attenuated oral) polio vaccine. Polio has been eradicated from many parts of the world thanks to widespread immunization.

Over the last twenty years: molecular genetics, immunology, microbiology, and genomics have increased implementations in vaccinology.

Latest accomplishments include the production of recombinant hepatitis B and reactogenic acellular pertussis vaccine. We have discovered new seasonal influenza vaccine production techniques too.

Timeline of Vaccines

Vaccine Miracles – Stories of Success

Vaccines have helped save millions of lives ever since their advent. Here are accounts of vaccine miracles that give hope for the future:

1. Smallpox

One of the most feared diseases, smallpox killed up to 30% of its affected. It left its survivors deeply scarred with no discovery of an effective treatment. In 1796, English physician Edward Jenner discovered how to use the cowpox virus to vaccinate people against smallpox. Vaccination programs expanded over the next century. The last case of it in the US dates to 1949. The smallpox immunization program ended in 1971. Globally, the final infection was in Somalia in 1977, and the WHO declared it eradicated globally in 1980.

In the history of the United States, smallpox has played a vital role in guiding the development of the country. When Europeans first came to the United States, they inadvertently introduced smallpox to the continent. As a result, it wiped out 95% of Native Americans.

The number of smallpox cases in the United States was around 110,000 between 1900 and 1930. Later on, the cases declined dramatically after the 1930s and there have been zero cases in the United States since 1950.

2. Polio

Mostly, this virus attacks children below three years old, and it can cause severe paralysis and death. Thanks to vaccines, much of it has been eliminated from the world since the 1950s and 1960s. However, cases still exist in several countries, and immunization programs in Asia and Africa continue.

Polio in the U.S.

The graph below shows the absolute annual number of cases and deaths reported in the United States over the past century. In 1916, the poliovirus infected more than 27,000 Americans while killing more than 7,000 people. At the same time, the cause and spread of the polio disease were not yet known. As a result, New Yorkers closed the schools, swimming pools, public theatres, etc. At that time, it was believed that the virus was spread by mosquitoes and cats. Over 72,000 cats were killed, and massive spraying of DDT insecticide was done to prevent the virus [[8]].

During the 1950s, there was a second major epidemic in the United States in which polio rose to 57,000. At this time, it was greatly facilitated by the successful development of the polio vaccine to hinder virus transmission. Since the 1960s, the cases and deaths from polio disease in the United States have fallen to zero. Now it is eradicated from the United States.

Figure 9: Data by Our World in Data [9]

Figure 10: Data by Our World in Data [10]

Figure 11: Data by Our World in Data [11]

1. Measles

Measles is a respiratory disease characterized by a rash. Measles is rare in America and other countries where vaccination is widespread, which is good because it can lead to pneumonia, encephalitis, or death. Approximately 10 million measles cases are reported yearly, with 197,000 deaths. However, if vaccinations were not available, the World Health Organization estimates that 2.7 million people would die from the disease each year.

Despite a 79% global drop in measles deaths between 2000 and 2015, 400 children still die from measles daily. From 2000 to 2015, with the global increase in routine measles immunization coverage, more than 20.3 million young lives have been saved. But there are some facts that you still don’t know about measles and its vaccine:

•       Measles kills over 568 people a day, especially children.
•       In 2019, over 207,500 people lost their lives because of measles.
•       A person infected with measles can infect around 12 to 18 people.
•       The measles vaccine has been available for about 50 years.

From 2000 to 2020, more than 31 million lives have been saved because of the measles vaccine[12].

Figure 13: Data by Our World in Data [14]

2. Hib Meningitis

It was once the most common cause of bacterial meningitis in children. However, since the development of vaccines for the disease in the 1990s, it has been nearly eradicated in developed countries. However, the picture isn’t so rosy in the developing world. Every year, Hib infects approximately three million people and kills an estimated 386,000, most of whom are children under five.

In the pre-vaccine era, the combined mean annual incidence of Hib disease among children under the age of 5 years was estimated to be:

•       40 per 100,000 population of Asia
•       41 per 100,000 population of Europe
•       60 per 100,000 population of Latin America
•       88 per 100,000 population of the U.S.[16]

After successful vaccination and prevention measures, the cases of invasive Hib disease have been reduced to 1.70 cases per 100,000 population from 2009 to 2015[17].

Figure 15: Data by Our World in Data [18]

3. Tetanus

Tetanus, also known as lockjaw, is prompted by the bacterium Clostridium tetani spores. When dirt enters a wound, an individual becomes infected. Infants could also become infected at birth due to a non-sterile delivery. Symptoms include stiffness and muscle spasms and can cause coma and death. However, its probability is one in a fifth. However, with increased vaccination rates, the disease’s incidence is decreasing globally.

In 2013, there were about 59,000 deaths from tetanus. It was less than 365,000 in 1990. In the United States, an average of 31 cases of tetanus were reported per year from 2000 to 2007. Most cases of tetanus among Americans are due to inoculations to lapse or immunized individuals[20].

Figure 18: Data by Our World in Data [22]

Some Vaccine Facts

After a lengthy reading of everything purely science, a bit of light reading on the fun facts about vaccinations can help one learn more. Here are some fun vaccine facts:

1. Did you know that? Vaccination is a centuries-old practice. In 1796, 100 years before viruses got discovered, Edward Jenner was the first to vaccinate in the Western world. Jenner used cowpox disease to prepare the immune system for much more lethal smallpox. Smallpox gets eradicated by an improved vaccine in 1979, but it killed over 300 million people worldwide during the twentieth century.
2. Before vaccines, people used variolation all around the world against smallpox.
3. The first-laboratory-produced vaccine was made for chickens in 1897 by Louis Pasteur.
4. The polio outbreak in the 1950s was the most recent virus to cause widespread closures of movie theatres and swimming pools.
5. Vaccines with weakened virus suspensions have been phenomenally successful.
6. Moderna was founded ten years ago to develop mRNA-based vaccines.
7. The World Health Organization estimates that 2.7 million people die from the disease yearly.
8. Smallpox came into the United States by Europeans. It wiped out 95% of the Native Americans.
9. Since 1950, there have been zero cases of smallpox in the United States.
10. In 1895, the first outbreak of polio disease in the United States had 18 deaths and 132 permanent paralyzes.
11. In 2003, polio-endemic countries were only four: Pakistan, Nigeria, India, and Afghanistan.
12. In 2019, over 207,500 people lost their lives because of measles.
13. More than 31 million lives have been saved from 2000 to 2020. All the credit goes to the measles vaccine.
14. In 2019, the Middle Atlantic region reported more cases of measles in the United States.
15. From 2009 to 2015, Invasive Hib disease has been reduced to 1.70 cases per 100,000 population.
16. There were 59,000 deaths from tetanus in 2013.
17. From 1980 to 2018, the reported cases of tetanus were reduced to zero.
18. The number of deaths caused by tetanus in the United States has not been more than 10 since 1996.
19. Around 82 percent of people in the Americas had received the third dose of Hepatitis B vaccination in 2020.
20. For the last 20 years, the vaccine for various diseases like diphtheria, measles, neonatal tetanus, pertussis, polio, and rubella, has controlled the number of cases and deaths from such viruses.

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