How Vaccinations Were Developed For Deadly Epidemic Causing Diseases And Their Role In Health Care

How Vaccinations Were Developed for Deadly Epidemic Causing Diseases and Their Role in Health Care

As of today, we are in a pandemic due to COVID-19. A pandemic is when an epidemic spreads across the world, affecting many people. Although COVID-19 may not be the most deadly viral infection, the mass spreading of it has changed the world completely. However, there have been many more harmful viruses which caused epidemics instead, for example: Smallpox, Polio, Mumps, Measles and Rubella. An epidemic is when a contagious disease affects many people in a particular region. Although these named diseases caused many deaths, the understanding of the body’s response towards these diseases has increased as a result of developing vaccinations

The human body deals with fighting diseases through the immune system. Pathogens, which are disease causing microorganisms, have chemical markers on their surfaces, called antigens. Antibodies stick to the surface antigen and destroy the pathogen in a number of ways. When a new pathogen enters the body, a primary immune response would happen. Depending on the severity of a disease, the time between the primary immune response and first contracting it may be fatal. Vaccinations prevent this from happening as they contain a weakened or dead microorganism. A vaccine increases protection towards a particular disease. They normally contain an agent which is similar to the pathogen which causes said disease. Although it is weakened, it still contains the same antigen. Therefore it will not be as harmful and it will still trigger a primary immune response. If a vaccinated person comes into contact with the real pathogen, antibodies would be produced much quicker and in a greater quantity, therefore destroying the pathogen before it can reproduce in mass.

The Development Of Vaccinations

The Development of Vaccines can be traced back through the history of various diseases that threatened mankind and how they were controlled via Vaccinations.

The first evidence of Smallpox dates all the way back to the Egyptian Dynasty. It is believed that Pharaoh Ramses V died due to smallpox as there were skin lesions found over his mummified body. Smallpox is caused by the Variola virus. This comes in two different forms the Variola Major Virus and the Variola Minor Virus. In the major strand, the epidemiologist René Najera said, “Your body would ache, you’d have high fever, a sore throat, headaches and difficulty breathing.” There would also be a fierce breakout of a rash, which causes severe irritation. The minor strand emulates much less severe symptoms and rashes.

There is an interesting story behind the development of Smallpox Vaccine. In 1774, a farmer by the name Benjamin Jesty noticed that the milkmaids were immune to smallpox. Instead, they were infected with cowpox. Cowpox is a disease fairly similar to smallpox, but it is significantly less severe. He scratched off and inoculated the cowpox pus into his wife and children. He noticed that they never contracted smallpox. It wasn’t until 1796 when his idea of inoculating people with cowpox became publicly known. Edward Jenner, who was a physician and a scientist at the time also noticed that milkmaids who contracted smallpox never had smallpox symptoms. In order to test this, he variolated these milkmaids. Variolation is the inoculation of the variola virus. These milkmaids showed no smallpox symptoms at all. To further test this, Jenner brought a milkmaid called Sarah Nelmes and his gardener’s son called James Phipps together. The significance of this is that Nelmes had cowpox sores. Jenner took material from Nelmes’ sores and inoculated Phipps with it. Soon after this, Jenner exposed Phipps to smallpox multiple times but he never contracted the disease. As a result of this, Jesty and Jenner’s hypothesis about inoculation was proven to be correct. In order to make his research and results publicly known, he published what he found. This spread all over Europe and it eventually got to King Charles IV of spain. Due to his influence, the King spread the findings throughout the world. In order to protect people from Smallpox, the physician

Alexander von Humboldt conducted an expedition to South America in 1803. Smallpox eventually got eradicated from the world in 1979. It is estimated that 300 million people died due to smallpox. This is how the world’s first ever vaccination was developed.

Although the Smallpox vaccination was the first one that was ever seen, the first Laboratory Developed Vaccine was made in 1879. Louis Pasteur developed the vaccine for Chicken Cholera. He discovered the building blocks to most modern day vaccinations attenuation. He was studying the progression of death through Cholera in chickens by injecting them with the full strength bacteria. Before he took a break, his assistant forgot to inject a chicken. A month or so later, the assistant injected one with this old, weakened bacteria and the chicken survived without showing severe symptoms. Pasteur injected the same chicken with fresh bacteria and it didn’t even show any signs of Cholera. Due to an accident, the process of attenuation was discovered. Pasteur is now known as ‘the Father of Immunology.’

Polio

With each threatening disease, scientists use new techniques to develop vaccinations. The next milestone is the Polio Vaccination and how the disease was conquered. Polio is an extremely contagious disease which attacks the central nervous system. It is transmitted through coughing, sneezing and specifically food and drink which is contaminated with faeces. There are 2 kinds of Polio - Paralytic and Non Paralytic. Only 1% of cases are Paralytic polio. Within this 1%, there are 3 different kinds of paralysis - Spinal, Bulbar and Bulbospinal.

Spinal polio is the most common with it taking 79% of paralytic polio cases. This happens when motor neurons in the spinal cord get destroyed. The motor neurons function is to connect muscles and organs together. They pass information through electrical impulses from the spinal cord to skeletal muscles. Upon infection of these neurons, they become inflamed and a group of motor neuron cell bodies (ganglia) get damaged or even killed. When this happens, Wallerian degeneration occurs. This is when the motor neuron’s axon detaches from the cell body. This severely weakens muscles as the nerves are now dead. Also, muscles will not get information as electrical impulses. As a result of this they become useless and therefore paralysed. This typically happens asymmetrically to the limbs, especially the legs.

Bulbar polio is the least common, with it taking 2% of all paralytic polio cases. It is much more severe than spinal polio as motor neurons in the bulbar part of the brain get destroyed. This part of the brain controls speech and most importantly swallowing. The point of swallowing is to stop foreign materials (food, liquids) from entering the oesophagus and therefore the lungs. With swallowing being harmed, saliva would be inhaled into the lungs at a much larger rate. When fluids build up in the lungs, it is similar to the effects of drowning. Also, due to these motor neurons in the brain being damaged, less electrical impulses would be travelling from the brain, therefore less coughing. Coughing is the body’s natural way to clear the airways. The bulbar part of the brain also controls the respiratory system. Most deaths from paralytic polio occur due to respiratory arrest. This happens from irregular respiratory rates. Irregular respiratory rates are when respiration is not happening enough for the body. This would also decrease the effects of gas exchange. If gas exchange completely stops for 5 minutes, vital organs will not get oxygen, therefore they would fail, leading to death. If gas exchange stops for even 3 minutes, it will lead to brain injury.

Bulbospinal polio takes up 19% of all paralytic polio cases. This entails both complications of spinal and bulbar polio. The spinal cord is split up into 3 sections cervical (upper), thoracic (middle) and lumbar (lower). Bulbospinal polio affects the cervical vertebrae. The phrenic nerve is attached to this vertebrae. This nerve travels down to the diaphragm, which is vital for breathing and gas exchange. Inspiration (breathing in) happens when the external intercostal muscles contract, therefore expanding the rib cage and making it move upwards. The diaphragm muscle contracts and moves downwards. Due to this movement, the thoracic cavity expands, therefore the thoracic volume increases. Due to pressure and volume being inversely proportional, the pressure inside the lungs decreases. This would make the air flow into the lungs along the pressure gradient. Due to the cervical vertebrae getting damaged, so would the phrenic nerve, therefore the patient would have to live off a ventilator for the rest of their life. The damaging of the phrenic nerve also affects gas exchange as it would eventually stop happening. Diaphragm paralysis means no inflation of the lungs. Ventilation moves air. If this cannot happen, carbon dioxide and oxygen concentrations in alveoli would reach equilibrium with the blood, therefore no net gas exchange. As a result of this, the only way of surviving is life on a ventilator.

Non paralytic polio entails flu like symptoms. 95% of the cases are asymptomatic. There is a 3-6 day incubation period for this.

The Polio Vaccination

There are 2 kinds of polio vaccinations: Formalin-inactivated Salk polio virus (IPV) and the Sabin Oral polio vaccine (OPV). The IPV was developed in 1952. It provides 90% immunity to all 3 strands of the virus. It was made by culturing all 3 strands in monkey kidney cells. Formaldehyde was used to inactivate and purify the vaccination. Formaldehyde is an organic anti toxin. An inactivated virus is when it gets cultured and killed so it cannot produce diseases. This vaccination is given in 5 different doses: At 8, 12 and 16 weeks old. After these, the person will get their next two at 3 years 4 months and 14 years of age.

The OPV was developed in 1961. It is taken orally. The way it was developed was from attenuation. An attenuated vaccination is when live viral particles are weakened enough to still trigger an immune response. They are made by culturing the virus in non optimal conditions. In the case of the OPV, Sabin used rat and mice cells to grow and attenuate the virus. The OPV provides longer lasting immunity because it triggers humoral and cell mediated immunity. Humoral immunity is when a phagocyte engulfs an extracellular pathogen. Extracellular pathogens do not invade our cells so it reproduces off bodily fluids. Phagocytosis would present antigen presenting cells (APCs) to T helper cells. These T helper cells release cytokines which stimulate B cells, which divide into B effector cells. When this happens, these B effector cells differentiate into plasma cells which secrete antibodies. Antibodies would therefore neutralise the pathogen. Cell mediated immunity is when the pathogen is displayed on the cell’s surface. T cells with specific antigen receptors would bind to it and activate the antigen. They divide by mitosis, therefore producing genetically identical daughter cells which differentiate into T helper cells or cytotoxic T cells. The function of cytotoxic T cells is to directly kill infected cells. This happens upon binding to a cell which has been infected by a virus. A cytokine called perforin forms pores in an infected cell’s cell membrane. Granzymes, enzymes that destroy proteins, get released and enter the cell via endocytosis. These granzymes start apoptosis, which lead to the fragmentation of the nucleus and cytoplasm, therefore killing the infected cell. This cytotoxic T cell is set free to kill other infected cells.

The OPV is not the regulation vaccine for polio anymore. It is only used in places which still have large issues with polio. These places tend to be LICs which have issues with sterility, therefore risking contamination with needles. It is also used as it protects the intestines much more than IPVs. This is significant as the intestines are the primary source of entry for polio. Until 1987, the OPV was primarily used to eradicate polio throughout the world. In 1987 they reformed the IPV and made it much more effective. It is now commonly used in the UK and the USA. With the help of these 2 vaccinations, this terrible disease made Europe, USA, China and Australia all polio free by 2002.

Measles, Mumps and Rubella

Another milestone in Vaccinations is control of 3 infectious diseases Measles, Mumps and Rubella. Rubella is a contagious disease which is spread by person to person interactions. It causes a red rash, mild fever and tender lymph nodes. Lymph nodes play an important role in fighting infection as they produce and store lymphocytes. The rubella virus is much more fatal upon pregnant women, especially if they’re in their first trimester. The virus would be transmitted through the bloodstream of the mother into the foetus. The virus could cause birth defects or be fatal in the worst case scenario. The common defects for children are deafness, cataracts, and heart problems. The complications are: Glaucoma, brain damage and chronically inflamed lungs. Glaucoma is when the optic nerve is damaged. The optic nerve transmits information as electrical impulses to the brain which gives us vision. If this is damaged then vision would irreversibly be lost. Brain damage happens when the brain cells get infected. This could lead to a brain haemorrhage, the bleeding of the brain. If there is less oxygenated blood in the brain, there would be a larger build up of pressure therefore killing brain cells. Chronically inflamed lungs would mean less gas exchange and respiration would happen. After someone contracts rubella, they are most likely to be permanently immune to it, however after women contract and recover, they typically get arthritis in their fingers and joints.

Measles is a highly contagious viral disease which entailed multiple epidemics before 1963. Scientists estimate that 2.6 million people died per year directly due to it. The measles virus is part of the paramyxovirus family. This means that it is an RNA virus which is transmitted very easily. The symptoms are: acute respiratory problems, high fevers and a rash around the respiratory tract. The measles virus infects the respiratory tract first, and then it spreads to the rest of the body. The complications are: measles keratitis, encephalitis and pneumonia. Measles keratitis is when the cornea becomes inflamed. If the patient stays in an illuminated area, the retina would be damaged. The retina’s function is to send light as electrical impulses to the brain which produce the image that was seen. If this tissue gets damaged, there would be no impulses to the brain, therefore no vision. Encephalitis is when a viral infection causes inflammation of the brain. There are 2 types of encephalitis: Primary and secondary. Primary encephalitis is when the brain is directly infected. Secondary encephalitis occurs after the immune system has an incorrect reaction to infected cells in the body. The immune system would attack healthy, non infected cells in the brain. Pneumonia is the inflammation of the alveoli in the lungs. Purulent drainage would fill up the lungs and therefore cause the drowning sensation and violent coughing. In pregnancy, if the mother contracts measles, there will not be any congenital anomalies. However, both the mother and child would be more susceptible towards the complications described above.

Mumps is a Homosapien exclusive disease which causes inflammation of the salivary glands. This disease is much less severe in comparison to measles and rubella. It typically only causes discomfort. ⅓ of the cases are asymptomatic. Some very uncommon complications are the inflammation of the reproductive systems. In males, the testicles become inflamed, which could lead to sterility. For females, the ovaries become inflamed, however this does not affect the ova at all. In the worst case scenario, mumps can cause meningitis. This happens when the 3 meninges membranes get inflamed. The meninges membranes are situated around the spinal cord and the brain. Due to this, septicaemia happens. This is when an immune response is so strong that it causes damage to your own organs. This poisons the blood therefore making it potentially fatal.

The MMR Vaccination

The MMR vaccination was made in 1971 by Maurice Hilleman. It contains 3 vaccines: Measles, Mumps and Rubella. The measles vaccine was released in 1963 by John Enders. He attenuated the virus by culturing it in cells which were not human cells. In this case he used embryonated chicken eggs. Due to this, the virus would have adapted to chicken cells and become weaker in human cells. This process took 3 years to work out, but when he finally injected it into a monkey, it produced a lot of antibodies. The significance of this is that there were no symptoms of measles at all. In order to check whether this was an anomalous result, they tested many monkeys. There were consistently no symptoms. In Enders’ team there was 1 physician by the name of Samuel L. Katz. Katz injected himself and Enders. The same thing happened with the monkeys no symptoms but many antibodies produced. In 1968 Hilleman developed an even more attenuated virus which he used in his MMR vaccination.

The mumps vaccine was released in 1967. Hilleman used a very similar method to Katz and Enders for this vaccination. He attained the virus from his daughter, Jeryl-Lynn’s throat as she had mumps at that time. Hence, the Jeryl-Lynn strain is used in mumps vaccinations to this day.

Hilleman also produced a Rubella vaccination, by using animal cells to attenuate the virus again. However, in the MMR vaccination he used Alan Plotkin’s vaccination as it was attenuated within human cells. Plotkin had 3 main goals: to make a particular strand of the Rubella virus weak (RA 27/3), to test whether the nasal vaccination would provide immunity for adults and children, and whether the vaccination gave arthritis to women.

In order to complete goal 1, he cultured the virus with foetal cells. These cells would now be infected with the virus. He also did sub cultivation. This is when any part of cells into which a cultivation is divided when the concentration of cells hinders the growth. The part of the cell taken out was put into a new, sterile environment which has all the nutrients that a cell would need in order to divide. These cells keep dividing by mitosis, so all the cells produced would be genetically identical daughter cells which contained the virus. This makes the new cells much less specialised than the older ones, meaning they have been successfully attenuated. However, Plotkin was unsure whether the attenuated virus would still infect people in close proximity to people who were vaccinated. In order to find this out, his team chose large families with many children all of different ages. His team measured each person’s antibody count, recorded it and then vaccinated one of the children. The results showed that the vaccinated child had a large increase in antibodies, however he did not have any symptoms. His family’s antibody count barely varied from its baseline levels, meaning that the vaccination did not affect people in close proximity of the child. They did the same with the nasal vaccine in 1969 which gave the exact same result. He expanded his experiment to 123 families (123 children vaccinated), which also gave the same results, meaning that the vaccination consistently worked. For the 3rd and final goal, Plotkin injected 10 nurses and nasally sprayed 12 nurses. None of the nurses complained about arthritis pains. He expanded his research to 50 nurses, which showed the same result again. Due to these consistent results, it was clear that the vaccination was safe for pregnant women. Hilleman’s vaccination gave women arthritis pains, therefore giving more of a reason to use Plotkin’s vaccination.

The MMR vaccination is a combination vaccine. It contains samples from all 3 vaccinations. This makes it more efficient and easy to distribute. There have been little to know side effects reported, the worst being a mild fever or a small rash. It is recommended by the NHS for children to have 2 doses of this the first being at 1 years of age and the second one being at 3 years and 4 months of age. The MMR vaccination gives 99% immunity to measles and rubella, with mumps’ immunity being at 88%. For women, the vaccination must be taken at least 1 month before becoming pregnant as, even though the rubella virus is severely weakened, it can still lead to birth defects or even miscarriages.

COVID-19

In 2019, the world came to a stand still by another pandemic COVID-19. This challenged scientists around the world to make new vaccinations in a short span of time. The world witnessed many new and old techniques of Vaccine development for COVID-19. COVID-19 is a highly contagious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It can be transmitted through coughing and sneezing. The symptoms are a high fever, persistent cough, fatigue and a loss of taste and smell. The complications are: Pneumonia, Acute Respiratory Distress Syndrome and fainting.

Acute respiratory distress syndrome occurs when there is a severe shortness, and rapid shallow breathing. This provides a build up of carbon dioxide in the bloodstream. If there is less oxygenated blood, less oxygen would travel to the vital organs. This could cause organ failure, which is potentially fatal.

Regardless of the severity of COVID-19, the muscles around the heart will be damaged, increasing the probability of heart failure. Another complication that COVID-19 creates is problems in the lungs. The type of pneumonia that is contracted causes severe damage to the Alveoli. The Alveoli is where the oxygenated blood and deoxygenated blood gets exchanged. This damage would decrease the total surface area drastically, therefore decreasing the rates of gas exchange.

The last long term complication of Covid-19 is its effect on the brain. COVID-19 can cause strokes and Guillain-Barre syndrome. This affects the nerves and causes numbness, resulting in an increase of probability to get Parkinson’s syndrome. This results in loss of nerve cells in the Substantia Nigra, which causes stiffness and shaking.

Although scientists are unsure how Alzheimer’s happens, it is believed that there is an increased risk of it occurring due to contracting Covid-19. As age increases, a patient with Alzheimer’s would tend to forget things that recently happened. The virus increases the ability of the blood cells to clot. Most of these clots happen in single cell thick capillaries. The single cell is called an endothelial cell. It is also permeable as the capillaries function is to exchange water, glucose, oxygen and amino acids. With clotting this would happen less frequently. However, scientists believe that these complications take a long time to affect the body. They also believe that this is a major reason for the damage to the heart’s muscle.

The COVID-19 Vaccination

In the UK, the COVID-19 vaccination has been developed in different ways by different pharmaceutical companies. The 2 general techniques used were: RNA vaccinations and Adenovirus Vector Vaccines.

The RNA vaccinations work by using an mRNA (messenger RNA) sequence. mRNA is formed via the process of transcri ption. DNA is double stranded. This double helix gets unzipped by an enzyme called DNA helicase as it breaks the hydrogen bonds between the complementary base pairings. Another enzyme called RNA polymerase attaches to the DNA strand. The RNA nucleotides bind to the DNA’s nucleotides, also due to complementary base pairings. This forms a strand of mRNA. This mRNA code would have a specific antigen coded for it. The immune system would react to this antigen as it is common between the mRNA strand and the real virus strand. Therefore it produces antibodies and memory cells for the real virus, which would be actively ready and used in an immune response if the real virus infects you. Cells are always making proteins. RNA vaccinations take advantage of this as the DNA strand is the template for protein synthesis. First, it must make mRNA, which has a specific antigen coded onto it. When this mRNA strand enters human cells, it is used as genetic information, therefore it produces antigens. The immune system would react to this antigen. There are 3 kinds of RNA vaccinations which are typically used: non replicating mRNA, in vivo self replicating mRNA and in vivo dendritic cell non replicating mRNA. In non replicating mRNA vaccinations, the mRNA is directly injected into the body for the cells to produce antigens. In vivo self replicating mRNA vaccinations is when there are multiple mRNA strands from the same DNA template being injected. This means that there would be more antigens produced from cells from a smaller amount of vaccination used. This is significant as it increases immunity and it is much more cost efficient. In vivo dendritic cell non replicating mRNA vaccinations, the dendritic cells are used. These are antigen presenting cells, meaning they are immune to infection by the virus. They present antigens on the cell’s surface. Other APCs get into contact with these, which produces a humoral immunity response. Cells would be taken out of the bloodstream and then infected with the RNA vaccination. This gets re-injected into the body, therefore producing an immune response.These take much less time to produce as they can be made in bulk. This is very important in the current climate as it is unknown whether there will be a large, unexpected outbreak of COVID-19. They are also the most effective and much safer in comparison to the others as there is no direct viral infection causing agent used in the vaccinations. Due to these reasons, Pfizer and Moderna use these methods in producing their COVID-19 vaccinations.

SARS-CoV-2 is an adenovirus, meaning it is very large and easy to genetically modify. Therefore cell division can be stopped through a genetic modification. For COVID-19 vaccinations, Oxford/Astrazeneca used this method. They genetically modified a chimpanzee adenovirus so it does not replicate. This was to make it enter our cells, but not use human cells as host cells as replication would not be possible. They added a coronavirus gene to the chimpanzee’s adenovirus DNA. This destroys the spike proteins on the coronavirus, which is significant as the spike proteins are used to penetrate human cell’s cell membrane in order for the virus to access and use it as a host cell.

In conclusion, the purpose of vaccinations is to protect human beings from harmful diseases by achieving herd immunity. Herd immunity occurs when the majority of the population is immune to an infectious disease, therefore producing indirect protection to people who are not immune to said disease. If 90% of the population is immune to a viral infection, then in theory every 9/10 people would be at no/low risk as they already have antibodies which are active to fight off potential infections. There is no set percentage of the population which needs to be immunised for herd immunity to work. However, depending on the level of contagiousness, the higher the percentage must be. In the context to COVID-19, as of 20th April 2021, below twenty percent of the population has had both doses of the vaccination in the UK. The majority of this is people older than fifty five years of age and people who are at higher levels of risk towards COVID-19. Although only a low percentage of the population has been fully vaccinated, 49.7% of people have had one dose. According to the NHS guidelines, upon having the first dose, the person must wait twelve weeks for the second one. As a result of this, in twelve weeks 70% of the population would be fully vaccinated. Within these twelve weeks, even more people would be getting their first dose. This cycle would keep continuing until herd immunity is achieved. Overall, before COVID-19, vaccinations save 2-3 million lives per year, making them a stapled component of the medical world.