Unit 4 – Immunology and Public Health Active Immunisation and Vaccination

Learning Intention: To learn about active immunisation and vaccination Success Criteria: By the end of the lesson I should be able to State that active immunity can be developed by vaccination with antigens from infectious pathogens. State that active immunity leads to immunological memory. State that vaccines can contain inactivated pathogen toxins, dead pathogens, parts of pathogens, weakened pathogens or antigens mixed with an adjuvant. State that antigens are usually mixed with an adjuvant to enhance the immune response. State that an effective clinical trial design should be randomised, double-blind and placebo control. State that group size is important to reduce experimental error and allow for statistical significance. State that herd immunity occurs when a large percentage of a population are immunised. Describe the importance of herd immunity in infectious disease control. State that non-immune individuals are protected due to a lower chance of them coming into contact with infected individuals.

Types of Immunity - note Active immunity- antibodies made by individual in two ways Natural Acquired Active – Antibodies made by individual in response to antigen Artificially Acquired - In response to vaccine. Two Kinds of Passive immunity- Antibodies given to individual Natural - Ingested with milk shortly after birth Acquired – injection of antibodies to combat a disease e.g. rabies

Active Immunity Naturally acquired active immunity occurs when a person is exposed to a live pathogen, develops the disease, becomes immune as a result of the primary immune response. Artificially acquired active immunity can be induced by a vaccine, a substance that contains the antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease. B & T cells are produced and some persist as memory cells. Antibodies are also formed.

Vaccine A vaccine is a preparation which is designed to illicit an immune response. There are 4 main types: - killed - attenuated - sub-unit - toxoid

Killed – the pathogen is destroyed and cannot replicate itself e. g Killed – the pathogen is destroyed and cannot replicate itself e.g. polio Attenuated – the pathogen has been altered so it cannot cause the disease e.g. measles Sub-unit – only the protein coat of the pathogen is used e.g. Hepatitis B Toxoid – the toxins produced by the pathogen are injected e.g. tetanus antigen

In all these cases, the antigen must be intact if an immune response is to be caused. The aim is for B cells to produce antibodies and cause what is known as a primary immune response. As we saw in a previous lesson, memory cells also remain to give a faster secondary immune response if we ever come across the pathogen again.

Clinical Trials A clinical trial is a type of medical research. It aims to find new and improved ways of preventing diagnosing Treating controlling illnesses. People are involved in the trial in a controlled and carefully planned way.

Clinical Trials Clinical trials are designed to answer questions - about a treatment or a procedure. The main questions are usually: Does it work? Is it safe? Does it cause side effects? How does it affect quality of life? Does it work better than existing treatments? What is the best dose to use?

Clinical Trials Vaccines are subjected to clinical trials just like any other pharmaceutical medicine They must be shown to be safe and effective when used in humans

Types of Vaccine Trials Randomisation Everyone taking part in a randomised trial is put into different groups at random. Usually decided by computer. There are usually two groups in a randomised trial. Only one group has the new treatment. The other, called the control group, has the standard treatment or a placebo. The research team can then compare results from the two groups. One reason that trials are randomised is so that the research team can't choose who goes into which group based on what they know about their patients. For example, they might put people who they thought were healthier or more unwell into a particular group. This precaution helps to increase the reliability of the results.

Placebo Controlled Trials A placebo is a dummy treatment. E.g. a pill that looks the same as the drug being tested but just contains sugar. People can sometimes feel better when they have a placebo because they think they are having a real treatment. This is known as the 'placebo effect'. Comparing a group of people taking a new treatment with a group taking a placebo can show if the new treatment is really having an effect. A truly effective drug will show better results than the placebo.

Double Blind Trials In a blinded trial, you won't know whether you are getting the trial treatment, or the standard treatment or placebo. They will both look the same. Trials need to be 'blind' because just knowing that you are getting a new treatment can affect how you respond to, and make the results unreliable. Often the health professionals on the trial who give you your treatment are also 'blinded', meaning they don't know which treatment you are getting either - so they can't be influenced by what they know.

Experimental Error At the end of the trial, results from the two groups, which must be of a suitable size to reduce the magnitude of experimental error are compared to determine whether there are any statistically significant differences between the groups

Mass vaccination Edward Jenner was the first person to develop a vaccine. He noticed that people who had contracted cowpox were more likely to survive the deadly smallpox virus. He injected someone with cowpox and then exposed them to smallpox. This was the first ever vaccine and is named after the latin word for cow – vacca

Clinical trials Watch the following videos and discuss as a class. 5 minute animation about clinical trials which mentions placebo, randomisation and double blinding http://vimeo.com/69337236 Randomised/control trials - simple introduction http://www.ndm.ox.ac.uk/richard-antrobus-universal-flu-vaccine Why scientific trials are necessary – Ben Goldacre on Homeopathy http://www.youtube.com/watch?v=TZiLsFaEzog

More videos Ben Goldacre on Placebo effect http://www.youtube.com/watch?v=wsFTgirKXHk How to run randomised control trials http://www.youtube.com/watch?v=U50VP6E2dYw Randomised control trials – Ben Goldacre http://www.youtube.com/watch?v=RzRs7cPrrfE

Who is Edward Jenner Watch the video http://www.bbc.co.uk/education/clips/z3d9wmn Use the worksheet and questions on Edward Jenner

Mass vaccination Through the use of vaccinations, smallpox is now eradicated around the world. We hope to eradicate more diseases using vaccination programmes.

More on vaccinations Watch the following videos: Bill Gates explains the use of vaccines to eradicate diseases - http://www.youtube.com/watch?v=JZvpF6gaGH4 Universal ‘flu vaccine - http://www.ndm.ox.ac.uk/richard-antrobus-universal-flu-vaccine

Learning Intention: To learn about active immunisation and vaccination Success Criteria: By the end of the lesson I should be able to State that herd immunity threshold depends on the disease, the efficacy of the vaccine and the contact parameters of the population. Explain how public health immunisation programmes establish herd immunity to a number of diseases. State that difficulties in establishing widespread vaccination include malnutrition, poverty and rejection of the vaccine by a percentage of the population. State that some pathogens have evolved mechanisms to evade the immune system. State that these mechanisms impact the effectiveness of vaccination strategies. State that some pathogens (including those causing malaria, trypanosomiasis and influenza) can change their antigens, avoiding the effect of the immunological memory (antigenic variation). State that HIV directly attacks lymphocytes which is the major cause of AIDS. State that tuberculosis (TB) survives within phagocytes and avoids immune detection.

Herd immunity Herd immunity is where most of a population have been immunised against a particular disease and they can offer protection to the few members of the population who haven't had the vaccination. This is because their chance of coming into contact with someone with the disease is minimal. There are many reasons why someone cannot have the vaccination.

Herd immunity threshold This is the percentage of the population who need to be immunised by the vaccine to offer protection for people who are not vaccinated. Disease Transmission Average number of secondary infections resulting from single index case Herd immunity threshold Diptheria Saliva 6 – 7 85% Measles Airborne 12 – 18 83 – 94 % Mumps Airborne droplet 4 – 7 75 – 86 % Whooping cough 12 – 17 92 – 94 % Polio Faecal-oral route 5 – 7 80 – 86 % Rubella 83 – 85 % Smallpox Social contact

Absence of herd immunity Some populations do not have herd immunity and this may be because of very different reasons; In developing countries, malnutrition and poverty prevent mass vaccination programmes In developed countries, adverse publicity about vaccines leads to parents choosing to not have their child vaccinated.

Box 1 shows a community in which no one is immunized and an outbreak occurs. Box 2, some of the population is immunized but not enough to confer herd immunity. Box 3, a critical portion of the population is immunized, protecting most community members.

Video Watch the following video on the effect of adverse publicity on the MMR vaccination http://www.youtube.com/watch?v=jfheO9H8CD4

Herd Immunity The principle of herd immunity applies to control of a variety of contagious diseases, including influenza, measles, mumps, rotavirus, pneumococcal disease.

Evasion Of Specific Immune Response Just as vertebrates have developed many different defences against pathogens, so pathogens have evolved elaborate strategies to evade these defences. One way in which an infectious agent can evade immune surveillance is by altering its antigens; this is particularly important for extracellular pathogens, against which the principal defence is the production of antibodies against their surface structures.

Antigenic Variation Antigenic variation is a change in surface antigens on an infectious organism to help the organism evade the immune systems of potential hosts. Organisms use a variety of tactics for changing the composition of the antigens on their surface. This evolutionary trick allows them to continue growing and spreading in populations, perpetuating their existence.

Antigenic Variation Antigenic variation is of interest for people in charge of developing vaccines and medications to prevent and treat infection.

Antigenic Variation Organisms like viruses, bacteria, and parasites all have an external envelope, with a series of surface proteins. When an organism enters a host for the first time, the immune system does not recognize any of the proteins and may allow the organism to multiply, creating an infection. The immune system will learn that those proteins are dangerous, and when the organism appears in the future, the body will go on the attack. It sees the proteins, recognizes them as a threat, and sends out immune cells to kill the organism.

Antigenic Variation Without antigenic variation, infectious organisms would quickly become extinct. Numbers of vulnerable people in the population would drop and the organisms would not be able to survive. If, however, the organism can change the proteins in future generations, it can adapt and start evading the immune system again.

Antigenic Variation Some organisms experience random mutations, which can occur at any time. Others actually program in antigenic variation. These organisms can switch proteins on and off to present a completely different antigen to the immune system.

Antigenic Variation Antigenic variation can happen through mutation. Some organisms are better at it than others. The influenza viruses are a notorious example; they change so much that people must design a new vaccine every year to inoculate people against the flu. malaria – antigenic variation occurs within a population Trypanosomiasis - Trypanosomes are insect-borne protozoa that replicate in the extracellular tissue spaces of the body and cause sleeping sickness in humans. They select from a range of genes for antigen production

Direct Attack on the Immune System The absence or failure of some component of the immune system results in increased susceptibility to infection. Successful pathogens have often found a way of mounting a direct attack on the immune system

Direct Attack on the Immune System By interfering with the host cell’s phagocytic response the pathogen blocks an essential step in the process E.g. the bacterium that causes TB is an intracellular pathogen as it survives inside phagocytes by stopping the lysosome fusing with the vesicle. The pathogen remains alive inside the phagocyte and avoids detection by the immune system Tuberculosis bacteria (green) within a phagocyte of the immune system

Direct Attack on the Immune System AIDS (acquired immune deficiency syndrome) is a deficiency disease caused by HIV HIV attacks lymphocytes using them for reproduction. Release of new viral particles destroys the lymphocyte. Antibodies are ineffective against the viral particles inside the cells

Questions What must a vaccine contain to be effective? What types of vaccination are there? What immune cells are essential to immunisations? Who gave the first ever vaccination? What is herd immunity? What does the percentage depend on? Give two ways a pathogen can escape the immune response Why do you think some people are HIV negative and not HIV positive? Give one feature a good clinical trial should have and explain why it is needed.

Group work Choose one of the following diseases and create a presentation to present to the class HIV Influenza Malaria Sleeping sickness TB

Things to think about in your presentation What is the disease? How is it caused? How is it spread? What are the symptoms? Where is the disease most common? Any cure? Prevention measures? What outcome will the disease have on a persons lifestyle?