What is immunisation?

Immunisation is the process whereby an individual’s immune system GLOSSARY immune systemThe cells, tissues and organs that assist the body to resist infection and disease by producing antibodies and/or altered cells that inhibit the multiplication of the infectious agent and provide resistance to disease. becomes protected against an infection. The purpose of immunisation is to prevent people from acquiring infectious diseases and to protect them against the associated short and longer-term complications of the disease. 

Vaccine refers to the material used for immunisation, while vaccination refers to the act of giving a vaccine to a person. Vaccines work by stimulating the body’s defence mechanisms against an infection. These defence mechanisms are collectively referred to as the immune system. Vaccines mimic and sometimes improve on the body’s protective response, helping the immune system detect and destroy the infection when it is encountered in the future without development of significant symptoms or complications. 

The immune system

To understand immunisation, we need first to understand the way in which the human body naturally protects itself against disease. 

Diseases come in many forms: some of the most lethal are caused by infectious pathogens such as bacteria GLOSSARY bacteriaA single-celled, microscopic organism without a distinct nucleus. , viruses GLOSSARY virusesViruses are submicroscopic infectious agents consisting of a nucleic acid (DNA or RNA) molecule surrounded by a protein coat. Viruses cannot replicate outside a living cell.  and parasites. Once they have invaded the body, they begin to attack and multiply. To combat infection by these pathogens, the body's immune system can marshal two main lines of defence—innate or natural immunity GLOSSARY natural immunityImmunity that is present in an individual at birth prior to exposure to a pathogen or antigen which provide an initial response against infection. , and acquired immunity GLOSSARY acquired immunityAcquired immunity results from the development of antibodies in response to an antigen, as from exposure to an infectious disease or through vaccination. .

These two lines of defence have different characteristics: 

• natural immunity has a more rapid response than acquired immunity;
• natural immunity responds in the same way to all infections by pathogens; acquired immunity responds in a specific way to each different infection;
• acquired immunity has a ‘memory’ of previous infections. There is some evidence that innate immunity can also have memory;
• natural immunity has the same level of response to each new infection; acquired immunity shows a much greater response to subsequent infections by identical microorganisms. 

Vaccination is a form of innate and acquired immunity. 

Often made up of killed or modified microbes, certain parts of microbes or even microbial DNA, vaccines trick the immune system into believing that an infection has occurred. The immune system then jumps in to action, attacking the (actually harmless) vaccine and thus preparing itself for any future invasions of the type of microbe contained within the vaccine. 

Immunisation is designed to block specific infection. This means that we need to have a separate vaccine for each infection. At present there are six major vaccine-preventable diseases—pertussis, childhood tuberculosis, tetanus, polio, measles and diphtheria. The capacity of the immune system to respond independently to each infection also explains why the system cannot be overloaded or damaged by giving the full range of currently available vaccines, or by having multiple antigens in one vaccine preparation. 

• Acquired immunity: the body's second line of defence

  The two potent weapons of acquired immunity are the antibody and the T-cell. They operate at different levels: antibodies at the molecular level and T-cells at the cellular level. 

  Antibodies 

  Antibodies are protein molecules that move freely in the bloodstream. They are manufactured by white blood cells in response to the presence of molecules on the surface of the disease-causing microorganism. These molecules are known as antigens. A particular antibody will combine best with the antigen that caused the production of that antibody: thus, the antibody is said to be specific for its antigen. Antibodies react chemically with these antigens in such a way that the microorganism or toxin is neutralised and destroyed before a cell is infected. 

  T-cells 

  At the cellular level, the body manufactures what are known as cytotoxic T lymphocytes—T-cells. These white blood cells recognise certain antigens produced by microorganisms and kill cells that harbour them. 

  If an invading microorganism evades the antibodies and infects a cell, the T-cells will recognise the infected cell and kill it. Thus the two weapons of acquired immunity, the antibody and the T-cell, complement each other. 

  Thanks for the memory 

  Once an infection has been overcome, antibodies and T-cells remain in the body, often for years and sometimes for life, acting as a kind of ‘memory’. If the microorganism attacks again, these antibodies ‘remember’ it. They combine with the antigens on the surface of the microorganism and immobilise it so it is no longer able to damage cells in the body. If, despite the efforts of the antibodies, some cells in the body become infected, the memory T-cells are mobilised rapidly to kill the infected cells. Thus, the body has acquired immunity against that particular disease. 

  Active immunisation 

  Vaccination works by introducing harmless versions of a disease-causing microorganism or certain antigens of it to the immune systems of uninfected individuals. It induces the same or better protective response than thenatural infection, causing the immune system to produce antibodies and, when required, T-cells specific to the microorganism.The body is thus equipped with the right armory should infection by the real microorganism occur. The vaccines used in vaccination are of several types: 

  • live, attenuated microorganisms;
  • killed microorganisms; and
  • only one, or a few, antigens of the microorganisms, such as a toxin (toxic molecule) which is first rendered safe (detoxified). This type is called a subunit vaccine and is a type of acellular GLOSSARY acellularA vaccine containing two or more antigens but no whole cells. vaccine. 

  Passive immunisation 

  Protection against some infections may be achieved by passive immunisation. With this type of immunisation, antibodies produced in one person are introduced into another. These antibodies are injected into the host shortly before the expected exposure to a disease-causing microorganism. The antibodies are obtained from the blood plasma of people who have had the disease (or have been immunised against it). Injection of the antibodies confers immediate protection against infection for a short time (weeks). It may also be effective if given shortly after such exposure; for example, after being bitten by a snake or rabid dog. 

Benefits and risks

Who benefits from immunisation?

Individuals, communities and whole populations can benefit from immunisation. 

An effective vaccine protects an individual against a specific infectious pathogen and its associated various complications. In the short term, the efficacy of a vaccine is measured by its capacity to reduce the overall frequency of new infections, and to reduce major complications, such as serious tissue damage and death. 

All vaccines currently in use in Australia confer high levels of protection that are sufficient to prevent disease in the great majority of vaccinated individuals, and in the wider community. For example, the pertussis vaccine prevents disease in 85 per cent of recipients, while the measles vaccine prevents disease in 95 per cent of recipients. The remaining individuals may not be fully protected and remain at least partially susceptible to infection. This may be due to genetic factors, or to the presence of other medical conditions that impair the capacity of the vaccine recipient to mount a protective immune response. 

Thus, in a given population, no vaccine will be 100 per cent effective: if a disease is prevalent in a community, some people who have been vaccinated may still contract it. 

Recent studies have indicated that the new acellular whooping cough vaccine, while giving fewer side-effects, may be slightly less effective than the traditional vaccine made from a killed, whole microorganism. 

An important feature of immunisation is that it brings benefits not only for the individual who receives the vaccine, but also for the entire population through a phenomenon called herd immunity. 

Herd immunity GLOSSARY Herd immunityA form of immunity that occurs when the vaccination of a significant portion of a population (or herd) provides a measure of protection for individuals who have not developed immunity. occurs when a significant proportion of individuals within a population are protected against a disease through immunisation. This situation offers indirect protection to people who are not vaccinated, or who were but whose immune systems did not respond to the vaccine, by making it less likely they will come into contact with someone who is carrying the pathogen. 

In the case of a highly infectious disease such as measles, more than 95 per cent of the population must be vaccinated to achieve sufficient herd immunity to prevent transmission if the disease recurs. 

An additional benefit of vaccination is economic. Cost-effectiveness of community immunisation programs is determined by measuring the benefits—in terms of cost and quality of life—that result from preventing illness, disability and death, and comparing them with the costs of vaccine production and delivery to the population. A striking example is the benefits of the polio vaccination. In the first six years after the introduction of the vaccine, it was calculated that more than 150,000 cases of paralytic polio and more than 12,500 deaths were prevented worldwide. This represented a saving of more than US$30 billion annually in 1999 dollars.  

Vaccination around the world

The World Health Organization (WHO) estimates that 2 to 3 million deaths from measles, tetanus, diphtheria and pertussis (whooping cough) are prevented every year due to vaccination. 

Global coverage and of these diseases has risen significantly since 1974, when the WHO Expanded Programme on Immunisation began. Within forty years, some diseases, such as polio, have been all but eradicated, while deaths from measles—a major child killer—have declined by 71 per cent worldwide.  
 

Despite these impressive figures, there is still work to do. Of the 21.8 million children around the world who are not fully immunised, 75 per cent of them live in just 15 countries.

In Australia, immunisation rates are high. Data from December 2014 shows that more than 92 per cent of five-year-olds are fully immunised. 

What are the risks?

Vaccination is not completely risk-free. Like other medications, there can occasionally be side-effects, but the vaccines currently used in Australia provide benefits that greatly outweigh the risks. Before vaccines are made available, clinical trials with increasing numbers of participants are required to study safety. After vaccines have been introduced in to the community, safety monitoring continues.

The vast majority of side-effects that follow vaccination are minor and short-lived. The most common side effects for all vaccine types are ‘local’ reactions at the injection site, such as redness or swelling. More general ‘systemic’ reactions can include mild fever or tiredness. These reactions are outward signs that the vaccine is interacting with the immune system to generate a protective response. The nature of these reactions varies, depending on the type of vaccine given. 

Serious side effects from vaccines are extremely rare. Potentially serious side effects, such as transient febrile seizures, have been reported after vaccination. However, such severe side effects occur much less often with the vaccine than they would if a person caught the infection itself. For example, about 3 in every 10,000 children who receive the MMR (Measles, Mumps, Rubella) vaccine develop a fever high enough to cause short-term seizures. In contrast, the risk of such a fever is more than 30 times greater among children who develop the disease—affecting about 100 in 10,000 children.

The frequency of side effects associated with some earlier vaccine preparations (no longer in use in developed countries such as Australia) was higher than with the current generation of vaccines. It is important to note that some alleged links between administration of certain vaccines and onset of diseases such as autism and autoimmune diseases have proven to be false.  

Vaccine safety has been examined in great detail in recent years by expert committees such as those convened by the US Institute of Medicine. Their findings show that the risks of side-effects are generally extraordinarily low. 

• A controversial history: opposition to vaccination in the past

  The practice of vaccination has always had its share of controversy. In 1806 John Birch, Surgeon Extraordinary to the Prince of Wales and Surgeon to St Thomas’s Hospital in London, wrote a paper entitled Serious reasons for uniformly opposing the practice of vaccination. He predicted that ‘we shall soon see what yet remains of popular opinion favourable to the cause of [smallpox] vaccination, vanish into thin air’. Instead the disease itself has vanished. 
  A hundred years later, in 1913, Britain’s National Anti-Vaccination League published a booklet entitled Is vaccination a disastrous delusion? The booklet condemned the practice as ‘a monstrous and indefensible outrage upon the common sense and sacred personal rights of every human being, and especially every Englishman’. 

  Current opposition to vaccination 

  The issue of vaccination is still controversial. Many developed countries have small groups of people who are anti-vaccination and often highly vocal. Some are parents with a child who has had an illness in the weeks following vaccination, especially with the traditional whooping cough vaccine made from a killed, whole microorganism. The illness may have been caused by the vaccine, or it may have been a coincidence. 

  Though some may be highly educated, very few in the anti-vaccine lobby have expertise in infectious diseases and immunology. It is entirely appropriate for parents to be concerned about the risks of vaccination, but they must be given the full facts. 

  The Australian Academy of Science has recently addressed contradictory information in the public domain by publishing The Science of Immunisation: Questions and Answers. It was prepared by a Working Group and Oversight Committee made up of Academy Fellows and other Australian scientists with internationally recognised expertise in immunology. 

  Major medical bodies support vaccination 

  All the major medical bodies, including the World Health Organization and national medical associations, have been very strong supporters of vaccination. Some countries such as the USA have formed National Vaccine Advisory Committees, and in the USA unvaccinated schoolchildren are not accepted in schools (with rare exceptions). Particularly in many developing countries, there are national immunisation days when millions of infants and young children are immunised. 

  The case for carrying out vaccination programs is strengthened by the increasing amount of solid evidence that they work, as exemplified by the smallpox, polio and measles eradication campaigns. The recent outbreaks of whooping cough and measles in Australia show that this country will lose its reputation for high standards of public health unless vaccination coverage is rapidly increased. 

What vaccines are made of

Vaccines generally contain two major types of ingredients: antigens and adjuvants. Antigens are designed to activate adaptive immune responses which include antibodies and/or T-cells against a specific pathogen or its toxin. Adjuvants amplify immune responses more generally, especially innate immunity which is important for the induction of adaptive immunity. 

Some vaccines comprise the killed whole pathogen (virus or bacteria) that the vaccine is designed to protect against. The virus is grown in the laboratory and killed by heat and/or chemicals to render it non-infectious. The injectable poliomyelitis vaccine is an example of this type of vaccine. 

Other vaccines contain only components of the pathogen as their antigens. These components can be prepared by purifying them from the whole bacterium or virus, or by genetically engineering them. Engineered vaccines include the hepatitis B virus vaccine and the human papillomavirus vaccine. 

Another group of vaccines is based on the toxin produced by the pathogen that causes the disease symptoms. The toxin is chemically treated to make it in to a harmless toxoid. The antibodies produced against this toxoid are still able to neutralise the toxin, and to prevent the disease from developing. Examples of this type include the tetanus and diphtheria vaccines. 

Some vaccines do contain an infectious micro-organism. These are called live vaccines. These micro-organisms are an attenuated (less pathogenic) form of the pathogen that the vaccine aims to protect against. Examples include the injectable MMR vaccine, the oral polio vaccine and the chickenpox vaccine. Alternatively, a live vaccine may contain a naturally occurring organism that is closely related to the pathogen, but does not cause disease in healthy humans. An example is the BCG vaccine against tuberculosis and leprosy. 

• The basics of making a vaccine

  Edward Jenner used the first vaccine 200 years ago. He injected people with cowpox, a mild disease, so they were protected against smallpox, a much more serious disease (Box 1). Since then, this practice of deliberately infecting people with a mild disease to provide protection against a more serious form of the disease has become commonplace. 

  To make vaccines that produce the mild form of a disease, the disease-causing agent (the pathogen) must first be isolated and then treated so that it stimulates an immune response in the body but does not cause the disease. 

  Obtaining the pathogen 

  Conventional methods of producing vaccines involve growing large quantities of the pathogen. Viruses, for example, are cultivated by infecting cells grown in tissue culture, while many bacteria can be grown on agar gels. The pathogen is then concentrated, purified and treated to inactivate its capacity to cause disease. 

  Inactivating the pathogen 

  The pathogen can be inactivated using one of several techniques: 

  • It can be weakened by ageing it or altering its growth conditions (such as by depriving it of an essential nutrient). This technique produces a live, attenuated (weakened) vaccine. The vaccines for measles, mumps, and rubella are prepared in this way. Because this vaccine is actually a living microbe, it multiplies within your body and therefore causes a strong stimulation of the immune system.
  • It can be killed with formalin or by exposure to a high temperature. This method produces a killed vaccine. The vaccine for typhoid is prepared in this way. Because killed vaccines don’t multiply in your body, you require a number of injections to produce a high enough level of immunisation to protect fully against the disease.
  • Parts of the pathogen (antigens) that stimulate an immune response can be separated from the pathogen and used as a vaccine. This produces a subunit vaccine. The Haemophilus influenza type b and the new whooping cough vaccine are prepared in this way. These vaccines are examples of ‘acellular’ vaccines because they don’t contain whole cells of the pathogen. 

  Adjuvants 

  Most killed vaccines do not work unless an adjuvant is added. Adjuvants strengthen the immune response in some way. Most adjuvants currently used are compounds containing aluminium. 

  New vaccines 

  Medical researchers continue to pursue new methods of producing vaccines, particularly using biotechnology and genetic engineering techniques. These techniques can eliminate the need to produce large quantities of the microorganism in order to make a vaccine. 

Eradicating disease

It is incredibly difficult to eradicate a disease… but not impossible. Global vaccination programs resulted in the successful eradication of small pox in 1980. 

• Smallpox: the eradication of a disease

  Just over 200 years ago an English physician, Edward Jenner, noticed that milkmaids rarely caught smallpox. He reasoned that this was because they had previously caught a similar but relatively harmless disease, cowpox. Few people infected with cowpox subsequently caught smallpox. Jenner tested his reasoning by infecting a young boy with cowpox then exposing him to smallpox. The boy did not develop smallpox, so Jenner repeated the process with others—this was the first use of vaccination. (The word ‘vaccination’ comes from Jenner's use of cowpox; the Latin word vacca means cow.) 

  Smallpox has been eradicated 

  In recent years, smallpox vaccine made from a similar virus, the vaccinia virus, has been used worldwide and smallpox has been eliminated altogether. The last naturally-occuring occurrence of the disease was in 1977, in Somalia. The last reported death due to smallpox occurred in 1978, when a British laboratory worker died as a result of accidental exposure to the live smallpox virus kept at a research institution. The World Health Organization declared smallpox eradicated in 1980. 

  Stores of smallpox 

  Since smallpox has been eradicated as a disease, the only sources of the virus are stored in a couple of high-containment laboratories. A specialist committee of the World Health Organization (WHO) suggested destroying these stores of the virus in 1986. However, a project to look at the DNA of the virus forstalled the destruction of the stores. 

  Now scientists are voicing arguments for and against the elimination of the virus. The most compelling argument for the destruction of the smallpox stores is the potential for terrorists to use the virus for biological warfare. Those against the destruction of the stores want the virus samples to be maintained for study. 
  The late Australian scientist Professor Frank Fenner, who was chairman of the WHO committee involved in the decision, maintained that the responsible action is to destroy the virus. (Even if the virus is destroyed, doses of the smallpox vaccine will be kept.) 

  In 2002 WHO voted to stop the destruction of remaining smallpox virus supplies. Stock of the virus will be used for research into new treatments and vaccine, and the live virus is held under very strict biosafety regulations at only two laboratories in the world - the Centers for Disease Control and Prevention in the USA, and the State Research Center of Virology and Biotechnology in the Russian Federation. The WHO is still considering the issues surrounding the destruction of the virus stock. 

  Was Jenner unethical? 

  Some people think that Jenner was wrong to try deliberately to infect a young boy with smallpox. At first glance, it seems as if Jenner callously used a small child as a human ‘guineapig’. 

  What Jenner did was actually not new; he carried out a practice called variolation, which was common in his time. Variolation worked this way. When a person was fit and healthy, they could be infected deliberately with smallpox because they would then have a better chance of surviving. It is quite likely that the ‘variolus matter’ (pus) was taken from people who were fairly healthy themselves, so the virus they used would probably be a weakened strain. 

  Certainly the method worked, and it was very popular. However, variolation was risky because people in contact with the variolated person could catch smallpox and a few variolated people got such a severe case of smallpox that they died. So while variolation was a fair bet, vaccination was a much safer bet. 

  What Jenner did was to treat the small boy with cowpox first, and then to variolate him in the normal way. When the boy did not develop smallpox, he knew he had found a method that was safer than variolation. At no time, then, did Jenner act in an unethical way.

In 1988, the World Health Organization, in partnership with UNICEF and the Rotary Foundation began a public health campaign to eliminate all cases of poliomyelitis (polio). Following intensive immunisation programs, cases dropped from hundreds of thousands to only 291 in 2012—a massive reduction of over 99 per cent. However, eliminating that final 1 per cent has been incredibly difficult. Post 2012 polio has begun to re-emerge in some areas. Conditions in countries such as Syria, Pakistan and Cameroon have allowed the disease to gain a foothold once more, and it has spread quickly to Afghanistan, Iraq and Equatorial Guinea. This re-emergence highlights the importance of consistent vaccination programs and continuous monitoring to keep the disease in-check. 

Future challenges 

Vaccine researchers are now working to develop vaccines against acquired immune deficiency syndrome (AIDS), malaria and tuberculosis, which collectively cause more than five million deaths worldwide per year. These infections have so far eluded conventional vaccine development as they require both require a T cell as well as antibody response, but recent trials into human immunodeficiency virus (HIV) and malaria are proving promising. New technologies and innovative methods for clinical trials are constantly emerging too. This collective research is helping vaccine researchers to better address the needs in a 21st century world that is characterised by increased human life expectancy, emerging infections and poverty in low-income countries.

Conclusion

While there are some rare complications that can result from vaccination, a far greater risk will arise if the immunisation rate against these diseases begin to fall. It is only when immunisation rates are high that Australian children—and the wider community—will be protected against polio, diphtheria, whooping cough or tetanus, diseases that only a few decades ago were greatly feared. We have already had a taste of low immunisation levels with the 2010/2011 outbreak of whooping cough. We need a shot in the arm—or maybe several—if we’re to halt such diseases in their tracks.