Vaccines

Describe features of the history of vaccination (1)

If a person was presented to an infection in a controlled way, their immune system could be primed, small dose of disease without getting the disease (well recorded, but success recorded in 1796)

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Describe features of the history of vaccination (2)

1796 - Edward Jenner demonstrated that inoculation with cowpox virus produced protection from infection with smallpox (similar viruses). Exposed people milking cows to smallpox (but were vaccinated)

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Describe features of the history of vaccination (3)

Successfully demonstrated that exposing a person to a small amount of cowpox would prevent smallpox (found in observations). But there was a lack of knowledge about immunology and microbiology

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Describe features of the history of vaccination (4)

1806s-1890s - Louis Pasteur produced vaccines against chickenpox, cholera, diphtheria, anthrax and rabies. Proved that micro-organisms were responsible for disease, was not spontaneous (germ theory, Koch’s postulate)

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Describe features of the history of vaccination (5)

Post Second World War - successful live viral vaccines developed using cell culture techniques. Understood viruses more, pandemics, live viral vaccines. Cell culture – viruses need cells to grow/replicate, propagation of viruses

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Describe features of the history of vaccination (6)

Fertilised chick eggs were also used for the propagation of viruses

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Describe features of the history of vaccination (7)

Present and future - new technologies constantly developing, recombinant protein vaccines, DNA and conjugate vaccines. Antibody recognises antigen – sequence of amino acids, used of recombinant technology

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Describe features for the importance of immunisation (1)

WHO - the two public health interventions with the greatest impact are clean water and vaccination. Vaccination is the most effective medical intervention in the world. Vaccinations prevent disease form happening

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Describe features for the importance of immunisation (2)

Humans are still infected with micro-organisms (still have colonisation) but that micro-organism doesn't go on to cause disease. Prevents emergence of disease by priming the immune system in advance

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What are the aims of the immunisation programme?

Need to decide overall aim - to protect those at highest risk (selective immunisation strategy) or to eradicate, eliminate or contain disease (mass immunisation strategy)

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Describe features of selective vaccination (1)

Vaccine doesn't need to be given to all, only to those at increased risk of disease. Travel e.g. Japanese B encephalitis. Occupational risk e.g. anthrax (exposure to asbestos)

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Describe features of selective vaccination (2)

High risk groups e.g. hepatitis B vaccine for neonates born to Hep B +ve mothers. Outbreak control e.g. hepatitis A (water borne) vaccine. Rabies vaccine not 100% effective (but always take the vaccine), yellow fever (spread by mosquitoes)

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Describe features of mass vaccination (1)

Either - eradication (disease and its causal agent have been removed worldwide e.g. smallpox - only found in lab cultures, only affects humans, remove reservoir of infection)

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Describe features of mass vaccination (2)

Elimination (disease has disappeared from one WHO region but remains elsewhere e.g. polio, in regions where vaccinations are difficult to achieve/deliver, could be due to formulation, conditions, difficult to maintain conditions of proteins)

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Describe features of mass vaccination (3)

Containment (the point at which the disease no longer constitutes a significant public health problem e.g. H.influenzae)

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What is the consequence of receiving a fraction of a vaccine?

People might not develop immunity (may fail)

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Describe features of herd immunity (1)

Only applies to diseases which are passed from person to person. For each disease there is a certain level of immunity in the population which protects the whole population because the disease stops spreading in the community

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Describe features of herd immunity (2)

A disease can eradicated even if some people remain susceptible. Herd immunity provides indirect protection of unvaccinated as well as vaccinated individuals

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Describe features of herd immunity (3)

Able to control humans (e.g. isolate infected people from general population)

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Describe features of herd immunity (4)

Not for vector borne diseases, diseases passed through inanimate objects (cannot be controlled)

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Describe features of herd immunity (5)

Only a certain number of people in the population need to be vaccinated to prevent emergence of disease in the population (changes depends on type of disease, some need 80% vaccinated, others may need 95% vaccinated)

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Give examples of vaccines for preventable diseases

Diphtheria, neonatal tetanus, pertussis, meningococcal C disease, paralytic polio, H.influenza B meningitis, pneumococcal infection, measles, mumps, rubella, varicella, HPV, hepatitis, influenza, TB

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Why are children the targets for vaccinations? (1)

Immune system is not fully developed (more likely to develop disease if they are infected)

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Why are children the targets for vaccinations? (2)

Present children with antigen whilst they are in B/T-cell development, more likely to develop memory cells (they are exposed to antigens prior to exposure to antigens in the environment)

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Give examples of vaccines which are given to people later in life

Vaccines in later life e.g. HPV vaccine (12-13 year old girls, potential for males to be vaccinated, STI), TB vaccination, hepatitis. TB – used to be one of the leading causes of death in world/UK (airborne)

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Why is the BCG vaccine no longer compulsory?

Disease is not prevalent in community, vaccination didn’t work well in community, still had a 10% chance of being infected despite being vaccinated. US – never had a compulsory vaccination programme for BCG

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What were the issues with the BCG vaccine?

BCG vaccination was developed in Japan – works well in South-East Asia (successfully development/tested in South East Asia, not tested on other ethnicities, genetic differences)

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State features of the flu vaccines

Annual, viruses change. Flu – generalised term for condition of the disease, many virulents cause disease, prevalent at different rates, antigenic variation occurs on protein coat of viruses, change to evade immune system

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How can we make vaccines better?

Explore genetic variation (people respond to vaccinations in different ways)

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What are the aims for an ideal vaccine? (1)

To produce the same immune protection which usually follows natural infection but without causing disease. To generate long-lasting immunity. To interrupt spread of infection

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What are the aims for an ideal vaccine? (2)

Exposure to antigen, elicit immune response which is protective when exposed to full organism, will not cause disease, want immunity to be long lasting (e.g. tetanus – one vaccine, hepatitis C – three vaccines), stop spread of infection

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What are the aims for an ideal vaccine? (3)

If infected, you can fight off organism but don’t pass it onto someone else

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Summarise the features of the immune response to an ideal vaccine (1)

Vaccine is taken up by APCs. Activates both T and B cells to give memory cells. Generates Th and Tc cells to several epitopes. Antigen persists to continue to recruit B memory cells and produce high affinity antibody

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Summarise the features of the immune response to an ideal vaccine (2)

Want cellular expansion of as many immune cells as possible. Vaccine made up of different epitopes. Antigen will interact with antigen receptor (B cells, T cells, APC). Want polycellular proliferation – more than one antibody produced

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Summarise the features of the immune response to an ideal vaccine (3)

Clonal selection theory. Results in polyclonal serum rather than monoclonal serum. Polyclonal antibodies aimed at micro-organisms.

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Summarise the features of the immune response to an ideal vaccine (4)

Cell proliferation and cell differentiation (plasma cells – produce antibodies, or memory cells - which stay in secondary lymphoid tissue).

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Summarise the features of the immune response to an ideal vaccine (5)

Primary antibody response formed (takes a long time for antibody to be produced, not many B cells, wait for sufficient B cells to proliferate in order to produce enough antibodies to detect antigens)

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Summarise the features of the immune response to an ideal vaccine (6)

Lay as many memory cells down as possible – secondary response when exposed to micro-organisms. Use of T cells

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State features of the primary and secondary immune responses

Primary immune response develops in the weeks following first exposure to an antigen (mainly IgM antibody). Secondary immune response is faster and more powerful (predominantly IgG antibody)

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What are the types of vaccines? (1)

Passive immunisation (antitoxins and immunoglobulins which provide immediate source of antibody)

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What are the types of vaccines? (2)

Active immunisation (live vaccines - attenuated/weakened organism which replicates in host, killed/inactivated/subunit vaccines - killed micro-organisms, inactivated toxins and other subunits)

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What are the types of vaccines? (3)

Passive immunisation – give the pre-formed antibody (e.g. tetanus), response will be fast, bind to protein toxin

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What are the types of vaccines? (4)

Active immunisation – actively promoting immune system to respond, two ways: live vaccine (weakened organism, alive enough to replicate, severely compromised using techniques culturing, chemicals etc), killed/inactivated/subunit vaccine

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What are the types of vaccines? (5)

As long as we preserve antigen which produces the immune response, bad side – may denature proteins and produce new antigens, use methods to remove cell wall/membrane, antigens found on the surface of organisms, recognised by the immune system

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Describe features of passive immunity (1)

Immunoglobulins are concentrated antibody preparations (given IM/IV) which provide immediate short-term protection against disease. Given to individuals who are at high risk of experiencing severe disease

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Describe features of passive immunity (2)

Or for developing serious complications from the disease. Provides immediate protection but this is short lasting (only a few weeks or months). They don't stimulate the immune system to produce any antibodies

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Describe features of live vaccines (1)

Attenuated strains which replicate in host (virus/bacterium has been weakened to reduce virulence so it can't cause disease in healthy people). Act like natural infections. Live vaccines are the closest to actual infection

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Describe features of live vaccines (2)

Elicit good, strong, long-lasting immune response e.g. yellow fever (live vaccine). Live vaccine not given to those who are immunocompromised (even an attenuated strain is not given – high risk group)

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What are the advantages of live vaccines?

Single dose often sufficient to induce long-lasting immunity. Strong immune response evoked. Local and systemic immunity produced

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What are the disadvantages of live vaccines?

Potential to revert to virulence. Contraindicated in immunosuppressed patients. Interference by viruses or vaccines and passive antibody. Poor stability. Potential for contamination

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Describe features of inactivated vaccines (1)

Either - suspensions of whole intake killed organisms (e.g. whole cell pertussis, influenza, rabies, Hepatitis A). Or acellular and sub-unit vaccines - contains one or a few components of organisms important in protection

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Describe features of inactivated vaccines (2)

E.g. acellular pertussis vaccine contains between 2-5 components of the whole cell pertussis bacteria. E.g. diphtheria toxoid. E.g. Hib polysaccharide

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What are the advantages of inactivated vaccines?

Stable, constituents clearly defined. Unable to cause the infection

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What are the disadvantages of inactivated vaccines? (1)

Need several doses. Local reactions common. Adjuvant needed (keeps vaccine at injection site, activates APCs). Shorter lasting immunity

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What are the disadvantages of inactivated vaccines? (2)

Not as effective as live vaccine (may only generate monoclonal response, required several doses to achieve enough memory cells/immune response). Whole intact kill organisms or sub-unit vaccines (antigens)

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What is the purpose of adjuvants in vaccines?

Keeps vaccine at injected site (allows more antigen to be focused/concentrated in one area, more likely for APC to come into contact with antigen, adjuvant itself also produces an immune response, activates APCs). Freund's adjuvants (mixture of oils)

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What is conjugation? (1)

The process of attaching the polysaccharide antigen to a protein carrier (e.g. diphtheria or tetanus) that the infant's immune system already recognises in order to provoke an immune response

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What is conjugation? (2)

Adding polysaccharide to peptide is a way of stimulating APCs (act as linkers to antigen)

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Describe features of combination vaccines

Makes it easier to give several vaccines to one time. Reduces both number of clinical visits and number of injections needed.

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Before combination vaccines are licensed, studies are carried out to ensure what?

That the immune response to any of the combined antigen is just as good as the response to the individual vaccines. Rates of adverse reactions are the same as they would be if the vaccines were administered separately

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Describe features of the vaccine composition (1)

Adjuvants (enhance immune response to vaccine e.g. aluminium salts). Preservatives (prevent bacterial/fungal contamination of vaccine e.g. thiomersal)

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Describe features of the vaccine composition (2)

Additives (stabilise vaccine from adverse conditions e.g. freeze-drying, heat, maintains vaccine's potency e.g. gelatine - need alternatives, not accepted by everyone)

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Describe features of the vaccine composition (3)

Residuals from manufacturing process (inactivating agents, antibiotics - prevent bacterial contamination during manufacturing process, egg proteins - some vaccine viruses are grown in chick embryo cells, yeast proteins)

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Describe features of the vaccine composition (4)

E.g. formaldehyde, neomycin, streptomycin, polymyxin B, influenza, yellow fever, hepatitis B vaccine

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Describe features of the vaccine composition (5)

Difficult to use heat sterilisation – would denature the vaccine. Difficult to use filters – large protein size. Adjuvants (effective, lack of knowledge about mechanism))

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Give examples of vaccines in the UK vaccination schedule

Diphtheria, tetanus, pertussis, polio, Hib, MenC, rotavirus, MenC, pneumococcal disease, MMR, HPV, shingles (various formulations - IV, liquids, nasal spray)

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What is a primary vaccine failure?

An individual fails to make an adequate immune response to the initial vaccination (e.g. 10% of measles and mumps vaccine recipients)

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What is a secondary vaccine failure?

An individual makes an adequate immune response initially but then immunity wanes over time (feature of most inactivated vaccines, need boosters)

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Give examples of common local reactions following immunisation

Pain, swelling, redness at injection site. Small nodules may form at injection site

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Give examples of common general reactions following immunisation

Fever, irritability, malaise, fatigue, headache, nausea, vomiting, diarrhoea, loss of appetite

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Describe features of the risk of reactions vs risk of disease (1)

Convulsions (rate after natural disease - 1 in 200, rate after receiving MMR vaccine - 1 in 1000). Idiopathic thrombocytopenia purpura (rate after natural disease - 1 in 3000, rate after receiving MMR vaccine - 1 in 22,300)

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Describe features of the risk of reactions vs risk of disease (2)

Sub-acute sclerosing pan-encephalitis (rate after natural disease - 1 in 25,000, rate after receiving MMR vaccine - 0). Death (rate after natural disease - 1 in 5000, rate after receiving MMR vaccine - 0).

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Describe features of the risk of reactions vs risk of disease (3)

MMR vaccine – risk of autism when used in combination (proved wrong)

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Summarise features of how we vaccinate

Natural infectious agent. Live attenuated organism. Killed organism (adjuvant). Protective antigen (adjuvant, carrier, peptide synthesis, gene cloning, anti-idiotype)

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Summarise features of why we vaccinate (1)

Control of infectious diseases through vaccination requires an understanding of the natural history and biology of the infection and the immune response. For most infections we cannot protect all children effectively without herd immunity.

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Summarise features of why we vaccinate (2)

Many queries can be answered by reference to basic principles about the mode of action of inactivated and/or live vaccines

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How would you know if a patient required a booster vaccination?

Blood test. Measure antibody level to determine if a patient requires a booster vaccine

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Vaccines

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