Vaccines Flashcards

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1
Q

what is variolation?

A

Variolation: Pus taken from a smallpox blister and introduced via a scratch to an uninfected person to confer protection.
- Practiced in Africa and Asia for centuries before first reports in Europe

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2
Q

how was variolation popularised in Europe?

A
  • Variolation in Europe was popularised by Lady Mary Wortley Montagu in the early 1720s, after she witnessed the practice in Turkey.
  • Tested on prisoners who were given freedom in return – some of the first clinical trials
  • Lady Mary’s children were inoculated and also members of the royal family
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3
Q

who is Onesimus and what did he do?

A
  • Onesimus, an enslaved African, introduced the principles of smallpox inoculation (practiced in sub-Saharan Africa) to his master, Rev Cotton Mather.
  • Promotion of inoculation saved many lives during an outbreak in Boston in 1721 (6 out of 280 inoculated died; 844 out of 5,889 non-inoculated).
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4
Q

what did Edward Jenner do in 1796?

A

Developed the principles of vaccination:
- infected a boy with cowpox, then infected the boy with smallpox, and the boy didn’t get smallpox
Found that infection with cowpox provides protective immunity without risk of significant disease

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5
Q

why did Jenner’s cowpox inoculation against smallpox work?

A
  • Cowpox virus and smallpox virus share antigens
  • Cowpox virus stimulates an immune response that cross-reacts with smallpox antigens – protection against human disease
  • Vaccination primes adaptive immune response to particular antigens so first infection produces a secondary response
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6
Q

what is the main goal of vaccination?

A

generation of long-lasting and protective immunity

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7
Q

what are the 2 key aims of vaccination to generate immunity?

A

Aim 1: Eradicate disease e.g. smallpox (which caused 400 million deaths in 20th century) officially eliminated in 1979

Aim 2: reduce incidence/transmission of disease

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8
Q

what factors favour global eradication of infectious diseases?

A
  1. disease is limited to human - no reinvasion by microbe from animal host
  2. no long-term carrier state - no reinvasion
  3. few unrecognised clinical cases - surveillance of incidence is possible
  4. one or few serotypes - a single vaccine is adequate
  5. vaccines for smallpox are stable, cheap and effective - programme can be worldwide and is cost effective, so likely to be undertaken
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9
Q

what is the impact of vaccination?

A

Great reduction in many diseases since vaccination introduced
- e.g. Measles vaccine (MMR) saved 17M lives since 2000

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10
Q

why is herd immunity important?

A
  • For infections spread by person-to-person contact, risk of disease to an unvaccinated person dramatically reduced if 80 – 95% population vaccinated.
  • Herd immunity only for disease spread by person-to-person contact e.g. tetanus
  • % population that need to be vaccinated depend on how transmissible infection is e.g. higher for measles and Covid
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11
Q

how do vaccines confer protection?

A

via the induction of antibodies:
- Vaccine is injected into muscle and taken up by dendritic cells
- Vaccine is transferred to nearest draining lymph node to activate T cells (CD4 and CD8)
- B cells will differentiate to plasma and memory cells to generate an immune response
- Memory is generated

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12
Q

what is neutralising antibody?

A

Antibodies that coat a pathogen can stop the pathogen sticking to host cells - this is called neutralising immunity as you don’t get an infection at all

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13
Q

what are the key features of effective vaccines?

A
  • Safe – vaccine must not itself cause illness or death
  • Protective – vaccine must protect against illness resulting from exposure to live pathogen
  • Gives sustained protection – protection must last for several years
  • Induces neutralising antibody – some pathogens infect cells that cannot be replaced (e.g. Polio virus infecting neurons), so neutralising antibody is essential to prevent such infection
    -Stop the infection occuring in the first place and prevents cellular damage
  • Induces protective T cells – some pathogens, mainly intracellular, are more effectively dealt with via cell-mediated responses
  • Practical considerations – low cost per dose, biological stability, ease of administration, few side effects
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14
Q

what are the 3 main types of vaccine?

A
  1. Attenuated pathogen - Virulence reduced so causes mild infection
    - Living – can replicate to an extent
  2. Killed pathogen – Unable to replicate, fixed with formaldehyde
    - Non-living
  3. Subunit – Molecular component(s) of pathogen
    - Non-living
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15
Q

what are the features of living vaccines?

A
  • Preparation – attenuation (not always possible)
  • Administration – may be natural e.g. oral - single dose
  • Mimics real infection e.g. Polio vaccine
  • Adjuvant – not required
  • Safety – may revert to virulence – some danger
  • Unsuitable for immunocompromised
  • Requires cold storage – not good in tropical countries
  • Cost = low
  • Duration of immunity = years
  • Full immune response: IgG, IgA, cell mediated (cytotoxic T cells for viral infection)
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16
Q

what is an adjuvant?

A

Adjuvant is an ingredient added to vaccines to enhance immune response by inducing inflammation
- e.g. aluminium salts, lipids, MatrixM (saponin)

17
Q

what are the features of non-living vaccines?

A
  • Preparation – inactivation of pathogen
  • Administration – injection, multiple doses
  • Adjuvant is required to enhance immune response
  • Safety – needs safe inactivation
  • Suitable for the immunocompromised
    -Can be used in tropical climates – cold storage not needed
  • High cost
  • Shorter duration of immunity
  • Immune response is limited: IgG, less induction of cytotoxic T cells
18
Q

why are attenuated live vaccines generally more effective?

A

Generally more effective – “real” infection at appropriate body site, induces appropriate immune response to the pathogen
- Mimics a real immune response

19
Q

what are the methods of pathogen attenuation in live vaccines?

A
  1. Serial passage through cell culture in vitro (viruses) e.g. polio Sabin oral vaccine – stops making virulence factors
  2. Serial passage in vitro (bacteria) e.g. BCG against Mycobacterium tuberculosis – stops making virulence factors
  3. Adaptation to low temperatures (viruses) – less effective to make virulence factors in warm human body climate
  4. Genetic manipulation e.g. Vibrio cholerae missing A toxin subunit – can no longer make toxins
20
Q

what are killed vaccines? what are its advantages/disadvantages?

A
  • Inactivated (e.g. by chemical treatment or heat) so unable to replicate e.g. polio Salk vaccine
  • “Safer”, but some side-effects possible
21
Q

what are subunit vaccines? what are its advantages/disadvantages?

A

vaccine consists of key protein from pathogen
- safer, fewer side-effects
- but require adjuvants, multiple injections, immunity may be shorter-lived

22
Q

what are the types of subunit vaccines? give examples

A
  1. Toxoid – chemically inactivated toxin e.g. diphtheria, tetanus
    - Toxin taken and inactivated
  2. Recombinant protein e.g. Hepatitis B antigen (expressed in yeast), Novavax (modified SARS-CoV-2 spike protein, expressed in baculovirus)
    - Can clone proteins from pathogens in the lab
    - Don’t have to purify from pathogen (easier, safer) less risk contamination
  3. Subcellular fractions – e.g. polysaccharide capsules of pneumococci – not as good at activating T cells so cannot make B memory cells
  4. Conjugate vaccines – polysaccharide linked to carrier protein (stimulates B and T cell immunity) e.g. N. meningitides C vaccine
  5. Peptide vaccines designed to stimulate cytotoxic T cells e.g. Human Papilloma Virus (HPV)
23
Q

what are recombinant vector vaccines? give example

A

genetically engineered viruses are used as vectors to express the pathogen’s antigen in host cells
- Use live attenuated virus/bacterium as a “vector” to express antigens from another pathogen e.g. vaccinia + Hep B. Latest HIV vaccines being developed also of this type
- E.g. AstraZeneca SARS-CoV-2 vaccine: Chimp adenovirus with SARS-CoV-2 “spike” protein gene

24
Q

what are DNA/RNA vaccines? give examples:

A

Use DNA or RNA to transiently express pathogen antigen in host cells
- DNA can be directly injected into muscle
- mRNA has to be enclosed in a lipid bilayer coat to be taken up by cells

Pfizer/BioNTech and Moderna SARS-CoV-2 vaccines: RNA encoding virus spike protein.
New mRNA vaccine for Respiratory Syncytial Virus (RSV): RSV fusion protein

25
Q

what is the advantage of recombinant vector vaccines and DNA/RNA vaccines?

A

Both recombinant vector vaccines and DNA/RNA vaccines generate immune responses similar to natural infection

26
Q

what scientific barriers/limitations are there to vaccines?

A
  • Complex life-cycle of pathogen
  • T cell immunity needed
  • High mutation rates
  • Many types of pathogen: pathogen has lots of serotypes/variants; mutates quickly. Infection doesn’t results in an effective immune response in some people.
  • storage: measles vaccine is effective, but heat sensitive so can’t be used in tropical countries
27
Q

what social barriers/limitations are there to vaccines?

A
  • Expense, lack of appropriate medical infrastructure, patient compliance
  • Personal/religious objections
  • “Fake news”
  • Decline in MMR uptake following discredited link to autism (Wakefield et al. (1998)). 140,000 deaths worldwide in 2018, outbreaks in USA etc. (> 1200 cases in 2019).
  • Conspiracy theories - objections to polio vaccine in Pakistan, SARS-CoV-2 in US, UK etc.
  • 140,000 deaths from measles in 2018. Vaccination rates not increased in last decade
28
Q

are vaccines effective?

A

yes, they are the most effective form of medical technology we have