VACCINES

 Edward Jenner (1749–1823), a physician from Gloucestershire in England, is widely regarded as the ‘father of vaccination’ (Milestone 2). However, the origins of vaccination lie further back in time and also further afield. In fact, at the time Jenner reported his famous story about inoculating young James Phipps with cowpox and then demonstrating immunity to smallpox, the procedure of ‘variolation’ (referred to then as ‘inoculation’), by which pus is taken from a smallpox blister and introduced into a scratch in the skin of an uninfected person to confer protection, was already well established.

Variolation had been popularized in Europe by the writer and poet Lady Mary Wortley Montagu, best known for her ‘letters from the Ottoman Empire’. As wife of the British ambassador to Turkey, she had first witnessed variolation in Constantinople in 1717, which she mentioned in her famous ‘letter to a friend’. The following year, her son was variolated in Turkey, and her daughter received variolation in England in 1721. The procedure was initially met with much resistance — so much so that the first experimental variolation in England (including subsequent smallpox challenge) was carried out on condemned prisoners, who were promised freedom if they survived (they did). Nevertheless, the procedure was not without danger and subsequent prominent English variolators devised different techniques (often kept secret) to improve variolation, before it was replaced by the much safer cowpox ‘vaccination’ as described by Jenner.

Two places in particular have been suggested as the original ‘birthplace of inoculation’: India and China. In China, written accounts of the practice of ‘insufflation’ (blowing smallpox material into the nose) date to the mid-1500s. Meanwhile, in India, 18th century accounts of the practice of inoculation (using a needle) trace it back to Bengal, where it had apparently been used for many hundreds of years. There are also claims that inoculation had in fact been practised in India for thousands of years and is described in ancient Sanscrit texts, although this has been contested.

Given the similarities between inoculation as practised in India and in the Ottoman Empire, it may be more likely that variolation, had its roots in India, and it may have emerged in China independently. However, given that the ancient accounts of inoculation in India are contested, it is also possible that the procedure was invented in the Ottoman Empire and spread along the trade routes to Africa and the Middle East to reach India.

Regardless of geographical origin, the story of inoculation eventually led to one of the greatest medical achievements of humankind: the eradication of smallpox in 1980. And of course, it inspired the development of vaccines for many more infectious diseases. (Nature 28/9/2020)

First generation vaccines are whole-organism vaccines – either live and weakened, or killed forms.[170] Live, attenuated vaccines, such as smallpox and polio vaccines, are able to induce killer T-cell (TC or CTL) responses, helper T-cell (TH) responses and antibody immunity. However, attenuated forms of a pathogen can convert to a dangerous form and may cause disease in immunocompromised vaccine recipients (such as those with AIDS). While killed vaccines do not have this risk, they cannot generate specific killer T-cell responses and may not work at all for some diseases.[170]

Second generation vaccines were developed to reduce the risks from live vaccines. These are subunit vaccines, consisting of specific protein antigens (such as tetanus or diphtheria toxoid) or recombinant protein components (such as the hepatitis B surface antigen). They can generate TH and antibody responses, but not killer T cell responses.[citation needed]

RNA vaccines and DNA vaccines are examples of third generation vaccines.[170][171][172] In 2016 a DNA vaccine for the Zika virus began testing at the National Institutes of Health. Separately, Inovio Pharmaceuticals and GeneOne Life Science began tests of a different DNA vaccine against Zika in Miami. Manufacturing the vaccines in volume was unsolved as of 2016.[173] Clinical trials for DNA vaccines to prevent HIV are underway.[174]

 mRNA vaccines such as BNT162b2 were developed in the year 2020 with the help of Operation Warp Speed and massively deployed to combat the COVID-19 pandemic. In 2021, Katalin Karikó and Drew Weissman received Columbia University's Horwitz Prize for their pioneering research in mRNA vaccine technology.[175] (Wikipedia 2024)

 Tuberculosis (TB) is an infection that most often attacks the lungs, but in infants and young children, affects other organs like the brain. A severe case could cause serious complications or death. TB is very difficult to treat when contracted, and treatment is lengthy and not always successful. 

 Hepatitis B virus is a dangerous liver infection that, when caught as an infant, often shows no symptoms for decades. It can develop into cirrhosis and liver cancer later in life 

 Polio is a virus that paralyzes 1 in 200 people who get infected. Among those cases, 5 to 10 per cent die when their breathing muscles are paralyzed. There is no cure for polio once the paralysis sets in – only treatment to alleviate the symptoms 

 Diphtheria infects the throat and tonsils, making it hard for children to breathe and swallow. Severe cases can cause heart, kidney and/or nerve damage. 

 Tetanus causes very painful muscle contractions. It can cause children’s neck and jaw muscles to lock (lockjaw), making it hard for them to open their mouth, swallow (breastfeed) or breathe. Even with treatment, tetanus is often fatal 

 Pertussis (whooping cough) causes coughing spells that can last for weeks. In some cases, it can lead to trouble breathing, pneumonia, and death 

  Haemophilus influenza type b is a bacterium that causes pneumonia, meningitis and other severe infections almost exclusively in children under 5 years old 

 Pneumococcal diseases range from serious diseases such as meningitis and pneumonia to milder but more common infections like sinusitis and ear infections.

Pneumococcal diseases are a common cause of sickness and death worldwide, especially among young children under 2 years old 

 Rotaviruses cause severe diarrhoea and vomiting, which can lead to dehydration, electrolyte imbalance and shock in young children. This can lead to death if treatment, especially fluid replacement, is not immediately started 

 
Measles is a highly contagious disease with symptoms that include fever, runny nose, white spots in the back of the mouth and a rash. Serious cases can cause blindness, brain swelling and death 

 Mumps can cause headache, malaise, fever, and swollen salivary glands. Complications can include meningitis, swollen testicles and deafness 

 Rubella infection in children and adults is usually mild, but in pregnant women it can cause miscarriage, stillbirth, infant death or birth defects. 

 Human Papilloma Virus usually has no symptoms, but some strains can cause cervical cancer – the fourth most common cancer in women. Almost all cases of cervical cancer (99 per cent) are caused by HPV. HPV can also cause genital warts in both men and women, as well as cancer on other parts of the body 

(UNICEF 2024)

Immunisations are safe and effective, although all medication can have unwanted side effects. You may experience minor side effects following vaccination. Most reactions are mild and go away quickly.

Common reactions to vaccination include:

• pain, redness, itching, swelling or burning where the needle was given
• mild fever that doesn’t last long

These are generally mild and usually last for 1–2 days.

Common side effects for each vaccine are also listed on the Vaccines pages. If you have any concerns about potential side effects of vaccines, talk to your doctor or nurse.

In general, most children who have had a reaction to a vaccination can be safely re-vaccinated. Speak to your doctor for further advice. They may refer you to Immunisation specialist services for more testing or precautions before receiving further vaccines.

You can reduce many of the common side effects by:

• drinking extra fluids
• resting
• taking paracetamol
• not overdressing if hot.

For most people, the chance of having a serious side effect from a vaccine is much lower than the chance of serious harm if you caught the disease.

Serious reactions to immunisation are rare. There is a very small risk of a serious allergic reaction to any vaccine. This is why you are advised to stay at the clinic or medical surgery for a period of time following your immunisation.

See your doctor or nurse as soon as possible or go directly to a hospital and inform of recent vaccination if:

• you have a reaction that you consider severe or unexpected
• you are worried about yourself or your child’s condition after vaccination
• you experience any of the below:

A severe allergic reaction which occurs suddenly, usually within 15 minutes, however anaphylaxis can occur within hours of vaccine administration. Early signs of anaphylaxis include: redness and/or itching of the skin, swelling (hives), breathing difficulties, persistent cough, hoarse voice and a sense of distress.

(relates to rotavirus vaccine)

This is an uncommon form of bowel obstruction where one segment of the bowel slides into the next, much like the pieces of a telescope.

There is a very small risk of this occurring in a baby in the first week after receiving the first dose of rotavirus vaccine. There is a smaller risk after the second vaccine dose.

The baby has bouts of crying, looks pale, gets very irritable and pulls the legs up to the abdomen because of pain.

Some young children (especially aged 1–3 years) are more prone to seizures when experiencing a high fever from any source (with an infection or after a vaccine). The seizure usually lasts approximately 20 seconds and very rarely more than 2 minutes.

(relates to shingles vaccine Zostavax®)

Very rarely a generalised chickenpox-like rash following Zostavax® vaccination may occur around 2–4 weeks after vaccination, which may be associated with fever and feeling unwell. This rash may be a sign of a serious reaction to the virus in the vaccine.

(Australian Department of Health and Aged Care 2024)

A virus is a chain of nucleic acids (DNA or RNA) which lives in a host cell, uses parts of the cellular machinery to reproduce, and releases the replicated nucleic acid chains to infect more cells. A virus is often housed in a protein coat or protein envelope, a protective covering which allows the virus to survive between hosts.

A virus can take on a variety of different structures. The smallest virus is only 17 nanometres, barely longer than an average sized protein. The largest virus is nearly a thousand times that size, at 1,500 nanometres. This is really small. A human hair is approximately 20,000 nanometres across. This means that most virus particles are well beyond the capability of a normal light microscope.

The exact structure of a virus is dependent upon which species serves as its host. A virus which replicates in mammalian cells will have a protein coat which enables it to attach to and infiltrate mammalian cells. The shape, structure, and function of these proteins changes depending on the species of virus. 

The viral genome is surrounded by a shield of proteins. The various envelope proteins will enable the virus to interact with the host cell it finds. Part of the protein coat will then open, puncture through the cell membrane, and deposit the viral genome within the cell. The protein coat can then be discarded, as the viral genome will now replicate within the host cell. The replicated virus molecules will be packaged within their own protein coats and be released into the environment to find another host. While many virus particles take a simple shape like the one above, some are much more complicated

  Some virus molecules have no protein coat whatsoever, or have never been identified making on. In some plant virus species, the virus is passed from cell to cell within the plant. When seeds are created within the plant, the virus spreads to the seeds. In this way the virus can live within cells its entire existence, and never need a protein coat to protect it in the environment. Other virus molecules have even larger and more complex protein coats, and specialize on various hosts.

 This is a complicated question. A cell is considered to be living because it contains all the necessary components to replicate its DNA, grow, and divide into new cells. This is the process all life takes, where it is a single-celled organism or a multi-cellular organism. Some people do not consider a virus living because a virus does not contain all of the mechanisms necessary to replicate itself. They would say that a virus, without a host cell, cannot replicate on its own and is therefore not alive.

Yet, by the definition of life laid out before, it seems that when a virus is inside of a host cell it does have all the machinery it needs to survive. The protein coat it exists in outside of a cell is the equivalent of a bacterial spore, a small capsule bacteria form around themselves to survive harsh conditions. Scientists who support a virus being a living organisms note the similarity between a virus in a protein coat and a bacterial spore. Neither organism is active within their protective coat, they only become active when they reach favorable conditions.

In fact, the only reason a virus affects us at all is because it becomes active within our cells. Further, a virus tends to evolve with its host. Most dangerous viruses have just recently jumped to a new species. The biochemistry they evolved to live within the other species is not compatible with the new species, and cell damage and death occur. This causes a number of reactions, depending on which cells were infected. The HIV virus, for instance, attacks immune cells exclusively. This leads to a total loss of immune function in patients. With the virus causing the common cold, the virus attacks respiratory cells and damages them as it does its work.

Yet, not all virus infections will be detrimental to the host. A virus that kills the host will be less successful over time, compared to a virus which doesn’t harm the host. A healthy host increases the number of virus molecules released into the environment, which is the ultimate goal of the virus. In fact, some virus particles may actually benefit the host. A good example is a form of herpes virus, found in mice. This virus, while it is infecting a mouse, provides the mouse with a good defense against the bacteria which carry the plague. While the mechanism is not clear, the virus somehow prevents the bacteria from taking hold in the mouse’s system.

 An adjuvant is an ingredient used in some vaccines that helps create a stronger immune response in people receiving the vaccine. In other words, adjuvants help vaccines work better. Some vaccines that are made from weakened or killed germs contain naturally occurring adjuvants and help the body produce a strong protective immune response. However, most vaccines developed today include just small components of germs, such as their proteins, rather than the entire virus or bacteria. Adjuvants help the body to produce an immune response strong enough to protect the person from the disease he or she is being vaccinated against. Adjuvanted vaccines can cause more local reactions (such as redness, swelling, and pain at the injection site) and more systemic reactions (such as fever, chills and body aches) than non-adjuvanted vaccines.

Aluminium salts, such as aluminium hydroxide, aluminium phosphate, and aluminium potassium sulphate have been used safely in vaccines for more than 70 years. Aluminium salts were initially used in the 1930s, 1940s, and 1950s with diphtheria and tetanus vaccines after it was found they strengthened the body’s immune response to these vaccines.

Newer adjuvants have been developed to target specific components of the body’s immune response, so that protection against disease is stronger and lasts longer.

In all cases, vaccines containing adjuvants are tested for safety and effectiveness in clinical trials before they are licensed for use in the United States, and these vaccines are continuously monitored by CDC and FDA once they are approved.