Vaccines Flashcards
(147 cards)
1
Q
Aims and LO Lecture 1
A
Aims
- Background on vaccines
- Vaccine development
- How do vaccines work?
- Developing immunological memory
- Vaccination programs and pandemics
- Types of vaccine
- Uses of vaccines
LO
- Describe the difference between passive and active immunity.
- Explain how vaccines work and the development of immunological memory.
- Discuss the different types of vaccines and their clinical applications.
2
Q
Brief history of vaccines, do not need to learn for exam but good to be aware
A
Thucydides Athens 430 B.C.
- Proposed the notion that an affected individual might pass on a disease to another individual who is not yet affected.
- Recognized that resistance was specific i.e. survivors of the Plague were resistant to further attacks of the Plague, but not to other diseases.
Smallpox inoculation in China and India 1500s
- Involved grinding up smallpox scabs and blowing into the nostril.
- Or scratching matter from a smallpox sore into the skin (scarification)
Edward Jenner 1790s
- Observed that milkmaids who had contracted cowpox were immune to the more severe smallpox.
- Inoculated an 8-year-old boy with fluid from a cowpox pustule.
- Six weeks later he intentionally infected boy with smallpox. As he predicted the boy was now immune.
Louis Pasteur 1880s
- Developed vaccine for cholera in chickens – first attenuated vaccine.
- Coined the term vaccine from Latin word vacca meaning cow.
- 1885 administered first vaccine to a human, a young boy bitten by a rabid dog.
3
Q
What are vaccines?
A
- Generally, contain either parts of microbes or whole microbes that have been killed or weakened so that they don’t cause disease.
- Take advantage of the body’s ability to learn how to eliminate disease causing pathogens that attack it and develop a memory for future exposures.
- The concept of vaccinations has been around for a long time.
4
Q
Cases of certain diseases before and after vaccines
A
5
Q
How are vaccines developed what do they keep in mind/ knowledge?
A
- Increased knowledge of key features for T and B-cell epitope recognition enables better vaccine design.
- Optimise for maximum activation of both humoral and cellular immunity.
- Use of adjuvants to help maximise antigen presentation and most productive immune pathways.
6
Q
During vaccine development, what do they look for in the discovery and exploratory/ preclinical stage?
A
7
Q
Tell me what the ideal vaccine would be…
A
- Give life-long immunity
- Be broadly protective against all variants of an organism
- Prevent disease transmission
- Induce effective immunity rapidly
- Be effective in all vaccinated subjects, including infants and elderly
- Transmit maternal protection to the foetus
- Requires few (ideally one) immunisations to induce protection
- Would not be administered by injection
- Be affordable worldwide, stable (no requirement for cold storage), and safe
8
Q
What is immunisation and what two types of immunity are there?
A
Immunisation is the process of eliciting a state of protective immunity against a disease-causing pathogen.
There is Passive and active immunity
9
Q
What is passive immunity acquired through?
Tell me its role in the immune response
A
10
Q
What is active immunity acquired through?
Tell me its role in the immune response
A
11
Q
Tell me the flow chain of events for immunisation with passive and active immunity
A
12
Q
When may passive immunity be used?
A
- Babies born with congenital immune deficiencies.
- Unvaccinated individuals exposed to botulism, tetanus, diphtheria, hepatitis, measles and rabies.
- Antiserum provides antidote against poisonous venom.
- Exposure to pathogen that can cause death faster than an immune response can develop
13
Q
Does passive immunity have a memory response?
A
Passive immunity has no memory response – it does not activate own immune response.
14
Q
What are the possible risks of passive immunity?
A
- Host immune system can mount an anti-isotype response if antibody from another species – systemic anaphylaxis.
- Activation of complement immune complexes through IgM or IgG – type III hypersensitivity reactions (abnormal immune response mediated by immune complex of antibody-antigen)
15
Q
Give an example of a disease that passive immunity has been used to treat and tell me about some treatment developments in this area
A
Ebola
- Zmapp is composed of 3 human monoclonal antibodies
- More antibodies been produced since Zmapp that work equally well
16
Q
Current research: COVID-19 antibodies
A
17
Q
how can active immunity be triggered?
A
- Active immunity can be triggered by either natural infection or artificial exposure to some form of pathogen e.g., a vaccine.
- The immune system plays an active role by inducing proliferation of T- and B-cells.
18
Q
What is the primary goal of vaccination?
A
Primary goal of vaccination is to offer long term protection by inducing a memory response.
19
Q
What is the principle of a vaccination?
A
The principle of vaccination is to mimic an infection in such a way to activate host immune responseand induce a long-lasting immunological memory.
20
Q
Tell me about innate immunity and the types of cells involved in this response
A
Innate
- Non-antigen specific.
- General immediate response.
- No immunological memory.
- NK cells, mast cells, eosinophils, basophils and phagocytic cell (macrophages, neutrophils, DCs)
21
Q
Tell me about adaptive immunity and the types of cells involved in this response
A
Adaptive
- Specific to antigen.
- Lag time from exposure to response.
- Immunological memory after exposure.
- T cells and B cells
22
Q
Innate Vs adaptive immune system
A
23
Q
The generation of immune response against a pathogen by vaccination follows several distinct steps, tell me about these steps
A
- Uptake of vaccine (consisting of either the entire pathogen or antigenic components) by phagocytes- innate immune system
- Activation and migration of professional antigen-presenting cells from infected tissue to peripheral lymphoid organs.
- Antigen presentation to T cells and B cells
- Activation of T and B cells
- Long-lasting protection against pathogen through development of memory cells.
24
Q
T-cell activation- recap
A
25
What T cells are more easily activated... Memory T cells or Naïve T cells?
Memory T-cells are more easily activated than naïve cells and are responsible for secondary responses.
26
Tell me about the four types of memory cell, their difference in location, circulation and function...
**1. Stem cell memory T cells** - found in secondary lymphoid organs, give rise to central memory T cells.
**2. Central memory T cells** – reside in secondary lymphoid organs.
**3. Effector memory T cells** – circulate among tissues.
**4. Resident memory T-cells** – settle in peripheral tissue for long term, first cells to respond to re-infection.
NB. Regulation of memory T-cell development and response remain a very active area of research.
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B-cell activation- recap
28
Tell me the role of memory B-cells in the immune response and how they lead to the generation of matured memory B-cells
* **Memory B-cells** have longevity and show a rapid and robust response to antigen re-exposure.
* In primary response, **naïve follicular B cells** are activated in presence of antigen specific **T follicular helper cells (TFH)** with in secondary lymphoid organs.
* B cell clonal expansion and differentiation produces **plasma cells** (produce protective antibodies) and **dormant memory cells**.
* **Affinity maturation** occurs within germinal centres through **somatic hypermutatio**n and **selection by TFH cells.**
* Generation of **affinity matured memory B-cells.**
29
What is immunological memory?
Immunological memory is the ability of the immune system to respond with greater vigour upon re-encounter with the same pathogen.
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Tell me about memory cells role in the secondary response
Memory cells confer **immediate protection** and generate **secondary responses** that are more **rapid** and of a higher **magnitude** than primary response.
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The primary goal of vaccination is to...?
A. activate the innate immune system
B. Is to transfer active ready-made antibodies
C. Offer long term protection by inducing a memory response
D. Provide immediate protection where exposure to pathogen has an immediate threat to life
C. Offer long term protection by inducing a memory response
32
The principle of vaccination is to mimic an infection in such a way to activate host immune response and induce a long lasting immunological memort, this involves...?
A. innate immune cells
B. Adaptive immune cells
C. Both innate and adaptive immune cells
D. Passive immunity
B. Adaptive immune cells
33
What might be some of the barriers to widespread vaccine coverage?
* Cost
* Transport
* Storage
* Anti-vaxxers
* Beliefs
* distribution
34
Why are vaccination programs so important?
They play an important role in reducing deaths from infectious disease, especially in children
35
What does the UK and US recommend about the number of adult and children to be vaccinated in vaccination programmes?
The US recommends 10 vaccines for children from birth to age 6.
The UK recommends 13 vaccines for children from birth to age 4.
36
Some vaccines require boosters, tell me about some examples
* Persistence of circulating maternal antibodies e.g., DTaP and MMR vaccine.
* To ensure adequate immune response e.g., polio vaccine.
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Vaccinations are not 100% effective, tell me some reasons for this
* Incomplete uptake of boosters.
* Small percentage may not respond.
* Immune deficiency.
* Poor uptake of vaccines due to health scares e.g., MMR and the (unfounded!) link to autism
38
What is Measles and what is it caused by?
Measles is a **respiratory system** **infection** caused by a **paramyxovirus** – aerosol transmission (highly contagious).
39
What does the introduction of the measles vaccine correlate to?
A decline in the disease
40
Tell me the difference in fatality rate between developed and developing countries with measles
Measles fatality rate in developed countries is 0.3% cases, in countries with poor healthcare/ nutrition this can rise to 28%.
41
Tell me about the MMR autism controversy
* 1998 The Lancet publishes a paper by Wakefield et al. proposing a link between the MMR vaccine and autism (was fully retracted in 2010 stating it was fraudulent and there’s no link between MMR and autism, but a decrease of MMR vaccine is still seen due to the media)
* Uptake of MMR \<70% in some areas 5 years post Lancet publication.
1998 – 56 cases of measles in England and wales.
2006 – first death seen for over a decade.
2008 – 1315 confirmed cases.
2012 – 2032 confirmed cases.
2019 – 810 confirmed cases.
42
What is **Herd immunity?**
immunity developed by a group of vaccinated individuals
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How does herd immunity work?
* Immunised majority allows few unimmunised in community (due to immature/compromised immune systems) to be protected from disease.
* When percentages of immunised individuals \>95%, this can potentially stop the infection completely
(this vary can slightly differ between different diseases. E.g., corona, heard immunity is thought to be between 80-90% but figures and proof still needs to be done to support this)
44
Tell me some impediments to achieving herd immunity
* Concerns regarding adverse side effects
* Costs of vaccines
45
Tell me some immunisations of the following groups...
* girls ages 12 to 13
* adults
* travelers
* works exposed to biological agents in work environment
**Girls aged 12 to 13.**
* HPV virus (cervical cancer)
**Adult immunisations.**
* Influenza
* Pneumococcal
* COVID-19
* **Travelers.**
* Depends on site of travel
**Workers exposed to biological agents in work environment.**
* Anthrax
* Smallpox
* Hepatitis B
46
What are the barriers to widespread coverage in the developed world?
**Developed world**
* Access and cost issues among certain populations
* Language barriers
* Failure to obtain booster shots or complete series
* Fears concerning vaccination
* Underestimation of disease risk
47
Tell me the barriers to widespread coverage in developing countries
**Developing countries**
Logistical issues:
* Storage requirements
* Poor infrastructure
* Lack of roads
Personnel issues: shortage of health care workers.
Conflict e.g., war in Syria.
48
Vaccines without vials, fridges or needles?
49
What is a pandemic?
Worldwide spread of a new disease
50
When does a pandemic occur?
Tell me about it
* Happens when a bacterium or virus becomes capable of spreading rapidly.
* As these are novel, humans may have little or no immunity against them.
* Increased travel and mobility have increased likelihood of new diseases spreading.
* Antibiotic resistance increases the risk of future pandemics.
51
Tell me about the coronavirus antigens
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Coronavirus spike protein
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COVID-19 vaccines
54
Tell me some general facts about the Influenza virus
55
What are the main influenza antigens?
* Haemagglutinin (HA)
* Neuraminidase (NA)
56
Tell me about **Haemagglutinin (HA)**
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Tell me about **Neuraminidase (NA)**
58
What are the types of influenza virus?
And what is each?
A, B and C
A and B are related to seasonal epidemics
C is just mild symptoms
59
Tell me about **Influenza A**: any subtypes, proteins, strains
**Influenza A –**
subtypes (H#N#)
Based on viral surface proteins
* hemagglutinin (H) Types H1-H18
* neuraminidase (N) Type N1-N11
Different strains seen
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Tell me about **Influenza B**: any subtypes, proteins, strains
**Influenza B –**
no subtypes
Lineages
* Yamagata
* Victoria
Different strains may be seen
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What is the internationally accepted naming convention for influenza viruses?
Type/Geog. Origin/strain #/Year isolated (H#N#)
62
What are the two mechanisms to generate variations in influenza?
* Antigenic drift
* Antigenic shift
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Whats **Antigenic drift**?
**Antigenic drift –** accumulation of point mutations eventually yields a variant protein no longer recognised by antibody to the original antigen
(e.g., seasonal flu which is why they are offered a new vaccine annually)
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Whats **Antigenic shift**?
**Antigenic shift –** reassortment of an entire ssRNA between human and animal virions infecting the same cell.
The surface proteins on the new influenza subtype are so different that human antibodies no longer recognise them and thus have no immunity.
65
Tell me some examples of some pandemics and some general facts about them
**Avian flu**
* 2006 Bird flu outbreak: H5N1.
: Millions of poultry killed.
: Showed poor transfer to humans.
: 248 humans killed worldwide.
* Still come cases due to antigenic drift
* In the UK
2013 - H7N9
2014 - H5N6
2016 - H5N8
**Swine flu**
* 2009 swine flu outbreak
* H1N1 (new strain).
* Passes with ease between humans affecting healthy young adults.
* Killed more than 18,500 people globally between April 2009 – August 2010 (confirmed in lab).
* Estimates suggest a much higher figure ~300,000, with majority of deaths in Africa and Southeast Asia. 457 deaths in the UK.
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When a set of vaccines were developed to protect against H1N1/09 Virus what did they contain?
Contained either inactivated or live attenuated vaccine.
67
Tell me about the potential for a universal flu vaccine
* Current strategy involves the WHO and other health organizations making a decision about which hemagglutinin (HA) and neuraminidase (NA) viral surface antigens to include in the vaccine design.
* Effectiveness of conventional flu vaccines varies tremendously from year to year, depending on how well that vaccine matches the strain and lineage of influenza viruses that emerge.
* A vaccine that offers universal protection against all flu strains has remained the Holy Grail for the field.
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**Summary II**
* Immunisation is the process of eliciting a state of protective immunity against a disease-causing pathogen – **Passive or Active.**
* The principle of vaccination is to mimic an infection in such a way to **activate host immune response** and **induce a long-lasting immunological memory** – involves both **innate** AND **adaptive** immune cells.
* **Herd immunity** - Immunity developed by group of vaccinated individuals.
* Two mechanisms generate variations in viral diseases:
: **Antigenic drift** – seasonal flu
: **Antigenic shift** – pandemics
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**LO III**
* **Describe the difference between passive and active immunity.**
* **Explain how vaccines work and the development of immunological memory.**
* **Discuss the different types of vaccines and their clinical applications**
70
What must a vaccine design look like?
i.e. what must a vaccine be and what must it be able to produce?
Vaccines must be **safe, effective** in preventing infection, and should be **achievable** in target population.
A vaccine that produces a **primary response** may not work as a vaccine unless it also induces a **memory response.**
71
With vaccines, the branch of immune response activated is crucial for what?
Vaccine success
72
Tell me the following about **influenza virus**
Its incubation period
When memory cells can be activated
What an effective vaccine must have
What type of immunity is it an example of
**Influenza virus**
* Short incubation period (1-2 days).
* Disease already underway before memory cells can be activated.
* Effective vaccine must maintain high levels of neutralising serum antibodies.
* Those at risk immunised each year.
* Example of **sterilizing immunity**
73
Tell me the following about **polio virus**
* Incubation period
* When memory cells are activated and what happens after that
* Which ages tend to be immunised with this vaccine
**Polio Virus**
* Longer incubation period (3 days).
* Sufficient time for memory B cells to respond to produce serum antibody titre for viral clearance.
* Memory cells differentiate into plasma cells and release high levels of antibody to defend host.
* Immunised at 1yr, 3yr and 14yr.
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Tell me about **Correlates of immune protection**
“correlates of immune protection” which lineage of immune response do we need to activate to overcome a pathogenic threat
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Common vaccine types currently it use
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State 7 vaccine types
1. Live attenuated
2. Inactivated or killed
3. Toxoid
4. Subunit
5. Conjugate
6. Recombinant vector
7. DNA
77
What are **Live attenuated vaccines** and give some examples
**Attenuated** micro-organisms have lost their ability to cause significant disease.
**Retain capacity** for **slow and transient growth** within inoculated host.
**Examples:** Oral polio vaccine, MMR vaccine, and Tuberculosis vaccine (bacilli Calmette-Guerin (BCG)).
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How is **attenuation achieved**?
* **Natural attenuation –** vaccinia virus (cow pox) inoculation used by Jenner.
* **Serial passage** and selection of mutants with reduced virulence or toxicity.
- Usually selected for preferential growth in non-human cells
* **Chemical mutagenesis** e.g. treating salmonella typhi with nitrosguanidine produced a mutant strain lacking some enzymes responsible for virulence.
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What are the advantages of **Liver attenuated** vaccines?
* Live vaccines can replicate in host similar to pathogenic counterparts.
* Provides a larger and more sustained dose of antigen.
* Results in increased immunogenicity and more efficient production of highly efficient memory cells.
* Give long-lasting humoral and cell mediated immunity
* Fewer and lower doses are required.
80
What are the disadvantages of **Liver attenuated vaccines**?
* Live vaccines require refrigerated storage.
* May develop symptoms of natural disease e.g. 48 cases in 75 million for measles vaccine – post vaccine encephalitis.
* Immunisation of immune-deficient children with live vaccines can lead to serious complications.
* Reversion to virulent form e.g. 1 in 2.4 million for Sabine polio vaccine.
81
Tell me about the **sabin polio vaccine**
* Given orally.
* Induces IgA response along with IgM and IgG.
* Consists of three attenuated serotypes of polio virus.
* Gives protective immunity to all three strains.
* Requires boosters, a total of three doses.
82
Tell me the following about the sabin polio vaccine...
* The Wt progenitor strain genome is made up of ... ntds
* The Sabin vaccine is different by ... ntds
* The reversion to virulent form can occur in .... and this causes ...
83
What is a technique now used as a safer way to make live attenuatedvaccines?
**Recombinant DNA technology**
84
Tell me the process to how live attenuated vaccines are made?
* Gene required for virulence is isolated.
* Virulent gene is either mutated or deleted from viral genome.
* Mutations are engineered so that reversion to virulent form is virtually impossible.
* E.g. development of vaccine against malaria – deletion of key genes p52 and p36 prevents productive infection in the liver
85
How are inactivated or killed vaccines made?
Provide some examples of vaccines made this way?
Whole organisms are inactivated or killed using either **chemical reagents** (e.g. formaldehyde, glutaraldehyde) or **heat.**
**Examples:** Pertussis (whooping cough), cholera, typhoid fever, inactivated polio vaccines (Salk), influenza and zika.
86
Are the pathogens in the 'inactivated or killed' vaccines still able to replicate? What are they critically important for?
Pathogen is **incapable of replication**, but **still allows immune response.**
Critically **important to maintain structure of key epitopes** on surface antigens during inactivation.
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What are the advantages of inactivated or killed vaccines?
* Inactivated vaccines tend to be safer than live vaccines.
* They are more stable and don’t require refrigeration – easier storage and transportation.
* Some may be freeze-dried.
* Commonly used against both viral and bacterial diseases.
88
What are the disadvantages of inactivated or killed vaccines?
* Failure to inactivate pathogen e.g. first batches of Salk polio vaccine.
* Exposure of virulent pathogen to those making the vaccine.
* Need to be administered by injection.
* Produce a weaker immune response than live vaccines – generally requires boosters to illicit immune response.
* Generally only induce humoral immunity and NOT cell-mediated responses as organisms don’t replicate in host.
89
What are **subunit vaccines**?
* Subunit vaccines consist of a **specific purified macromolecule** from pathogen.
* Presents an antigen to the immune system without introducing viral particles.
90
What are the three main strategies for subunit vaccines?
Provide examples...
Three main strategies are:
1. **toxoids**
2. **isolated capsular polysaccharides**
3. **purified key recombinant protein antigens.**
**Examples:** Hepatitis B, Streptococcus pneumonia, diphtheria and tetanus.
91
The bacterial pathogens which cause **diphtheria** and **tetanus** produce what and what are these?
Bacterial pathogens causing diphtheria and tetanus produce **exotoxins.**
**Exotoxins** are toxins secreted by bacteria that can damage host and account for symptoms of disease
(NB. Toxoid vaccine)
92
Tell me about **Toxoid vaccines?**
Provide examples
**Toxoids:** Exotoxin is purified and then inactivated chemically with formaldehyde to eliminate toxicity whilst maintaining immunogenicity.
**Examples:** Diphtheria and Tetanus toxins.
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What do anti-toxoid antibodies do?
Anti-toxoid antibodies bind to and neutralise effect of exotoxin.
94
In the **bacteral capsular polysaccharide vaccines**, what does some pathogenic bacteria rely on?
Some pathogenic bacteria rely on the **anti-phagocytic properties** of their **hydrophilic polysaccharide capsule**
95
With bacterial capsular polysaccharide vaccines, what can you coat the capsule with and what does this increase?
Provide an example for this type of vaccine?
Coating capsule with **antibodies and/or complement** increases ability of macrophages and neutrophils to phagocytose these pathogens.
**Examples:** Current vaccine for **Streptococcus pneumoniae** consists of 13 antigenically distinct polysaccharides
96
What does the **Neisseria meningitidis vaccine** consist of?
Neisseria meningitidis vaccine, cause of bacterial meningitis, consists of **purified capsular polysaccharides**
97
Provide some advantages for subunit vaccines?
* Subunit vaccines don’t expose host to whole pathogen.
* They are relatively easy to produce and are stable.
* Generally safer and better tolerated than whole organism vaccines.
* Can be given safely to immuno-suppressed people.
98
Provide some disadvantages for subunit vaccines
* Generally requires strong adjuvants which can often induce a tissue reaction.
* Duration of immunity is generally shorter than live vaccines.
* They often need to be linked to carriers to enhance immunogenicity.
* Several doses must be given for proper life-long immunity.
* Induce little cell-mediated immunity.
99
What is an **adjuvant**?
Adjuvants: any material that can increase the humoral and cellular immune response against an antigen.
100
Inactivated, subunit or recombinant vaccines tend to have what type of immunogenic ability?
Poor immunogenic ability
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What do adjuvants do to immunogenicity of vaccines and what side effects does it have?
Adjuvants used to **augment and modulate immunogenicity of vaccines** without causing adverse effects.
102
What immune response do adjuvants stimulate? What do they act on and what does this lead to?
Adjuvants stimulate the **innate immune system** directly by acting on dendritic cells, macrophages, and neutrophils – leads to activation of adaptive immune system.
103
Tell me some characteristic properties of adjvant vaccines?
104
Adjuvants stimulate the immune system by sevel mechanisms, tell me what these mechanisms are and a bit about them?
Adjuvants stimulate the immune system by several mechanisms:
1. **A depot effect** (slow release of antigen which is supposed to provide continual stimulation to the immune system which is expected to amplify and sustain the immune response)
2. **Attraction and stimulation of antigen presenting cells**
3. **Inflammasome activation** (Inflammasome activation is known to trigger cleavage, activation and secretion of pro-inflammatory IL-1β and IL-18, which then recruit different types of effector cells and coordinate the innate immune response)
4. **Improve delivery of the antigen**
105
Name an adjuvent that was initially used in vaccines in 1930s-1950s and what it was used for?
* **Aluminum salts (Alum):** aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate.
* used safely in vaccines for more than 70 years.
* initially used in the 1930s, 1940s, and 1950s with **diphtheria and tetanus vaccines.**
106
Why have newer adjuvants been developed?
* Newer adjuvants have been developed to target specific immune components.
* provides stronger and longer lasting protection against disease.
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What are some side effects that adjuvant vaccines can cause?
* Local reactions such as redness, swelling, and pain at the injection site.
* Systemic reactions such as fever, chills and body aches.
108
Examples of adjuvant vaccine components, description and the vaccine products they were approved for
109
What is the problem and solution to **conjugate vaccines**?
* **Problem:** Some vaccines are poorly immunogenic i.e. produce a weak immune response.
* **Solution:** fuse a highly immunogenic protein to the weak vaccine.
* **E.g.** Haemophilus influenza type b (Hib) vaccine
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What is Hib (Haemophilus influenza type b) a major cause of?
What does the conjugate consist of?
What is activated?
What does it NOT induce?
* bacterial meningitis
* Conjugate consists of **type b capsular polysaccharide** linked to tetanus toxoid (highly immunogenic).
* Activates **THelper cells and memory B-cells.**
* Does NOT induce **memory T cells specific for pathogen.**
111
What does **Multivalent subunit vaccines** induce?
Tell me about it?
Tell me about the **solution** to multivalant subunit vaccines?
What is shown?
* To induce both a **humoral and cytotoxic T lymphocyte mediated response**, vaccine must be delivered intracellularly.
- peptide processing
- presentation by MHC class I
* **Solution:** incorporate antigens into lipid vesicles.
- Liposomes: proteins incorporated into bilayer with hydrophilic residues exposed.
- Immunostimulating complexes (ISCOM); antigenic proteins inside phospholipid monolayer.
* Show increased immunogenicity and fuse with plasma membrane to deliver antigens intracellularly.
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What are some new vaccines being developed?
What are experimental vaccines being developed?
**New vaccines**
* Recombinant viral vector vaccines.
* Nucleic acid vaccines
**Experimental vaccines**
* Therapeutic vaccines-cancer
113
Why is the **Recombinant viral vector vaccine** being developed?
Maintain the advantages of live attenuated vaccines while avoid the major disadvantage of reversion.
114
Tell me about the recombinat viral vector vaccines
* **Antigen encoding genes** of virulent pathogens expressed in safe attenuated viruses or bacteria.
* Carrier organism acts as a vector for pathogenic antigen.
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Name a recombinant viral vaccine that has been developed?
**Vaccinia virus widely** employed as a **vector** for new vaccines.
116
Tell me about the Vaccinia virus vaccine
* Can be engineered to carry several dozen foreign genes.
* Administered simply by scratching the skin causing a localised infection.
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More information regarding the Vaccinia vaccine...
118
The AstraZeneca/ Oxford University ChAdOx1 nCoV-19 vaccine
119
Another example of a recombinant vector vaccine...
Whats the Vaccine vector and the antigen?
* **rVSV-ZEBOV vaccine** used in West African Ebola outbreak (first one to be approved for use in 2020)
* **Vaccine vector:** vesicular stomatitis virus.
* **Antigen:** Ebola virus surface protein.
120
What do **Nucleic acid vaccines** involve the administration of?
Give examples for this
Nucleic acid vaccines involve administration of **genetic material encoding the desired antigen.**
1. **plasmid DNA**
2. **messenger RNA**
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How are most DNA vaccines administered?
Via Intramuscular injection or gene gun
122
Why are most DNA vaccines administered the way they are?
* muscle avidly takes up DNA.
* relatively low turnover rate of muscle cells prevents dispersion in dividing cells
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In nucleic acid vaccines, what are the **encoded antigens** expressed by?
Host cell
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What is the immune response in nucleic acid vaccines against?
Against the expressed antigen
125
Are many DNA vaccines under development?
Yeah
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What are the disadvantages of a gene gun for nucleic acid vaccines?
Gene gun: Expensive and developing countries may not be able to have it. generally, only good for therapeutic purposes
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Clinical trials for nucleic acid vaccines
128
Give some examples of some nucleic acid vaccines already in use
**Examples include:** Hepatitis B, malaria, HIV, Influenza, Zika, Dengue fever, Herpes and cancer, and Coronavirus.
129
Tell me about DNA vaccines
Plasmid DNA is maintained for long period **episomally** (extra chromasomally, float about in cell when delivered and helps facilitate immune response)
* Facilitates memory response.
Antigen is expressed by **muscle and dendritic cells at point of injection**.
130
DNA vaccines can take one of two routes when injected, tell me about the routes
131
With DNA vaccines, what does antigen expression engage?
The **B-cell receptor** to stimulate the humoral response
132
With DNA vaccines, expressing in dendritic cells is important for what?
Expression in dendritic cells important for antigen presentation by **MHC I and MHC II** for **cytotoxic T lymphocyte response.**
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What do DNA vaccines consist of?
DNA vaccines consist of **bacterial plasmids** into which specific sequences are incorporated.
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What is gene expression in DNA vaccines commonly driven by? What does this ensure?
Gene expression is commonly driven by the **cytomegalovirus immediate early promoter** and its adjacent **intron A sequence.**
ensures high transcription **efficiency.**
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Tell me some other element of DNA vaccines?
Other elements include a transcription termination signal and a prokaryotic antibiotic resistance gene.
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Parameters for optimising DNA vaccine design
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Tell me how DNA vaccines stimulate the innate immune system...
**Stimulation of innate immunity**
* Bacterial DNA stimulates the innate immune system.
* **DNA** acts as a **pathogen-associated molecular pattern** to stimulate cells through
* **Toll-like receptors** (TLRs).
* TLRs have an important role in the recognition of microbial components.
* **Hypomethylated CpG** dinucleotide that is common in bacterial DNA binds to **TLR9**.
* Stimulation of a range of TLR9-expressing cells, including B cells and dendritic cells.
- leads to a cascade of activation, proliferation and differentiation of natural killer cells, T cells and monocytes/macrophages.
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What are DNA vaccines being developed to treat?
Cancer
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Tell me some advantages and disadvantages of DNA vaccines
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Tell me some advantages of mRNA vaccines as opposed to DNA
* mRNA vaccines appear to perform better
* Does not need to enter nucleus since exerts function in cytoplasmic compartment as here it’s made into the protein
* Safer – no possibility of integration into host genome.
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Tell me a disadvantage of mRNA vaccines
* Stability – requires storage at -80 °C or -20°C
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Tell me how mRNA vaccines work
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Why is the mRNA vaccine packaged?
Give some examples of this packagin
Protect RNA from extracellular degradation which increases stability and also aids entry into host cell.
Examples of how to package mRNA molecules:
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What is a therapeutic vaccine?
Vaccines can also be used to treat already established diseases – therapeutic vaccines.
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Tell me about cancer vaccines (therapeutic vaccine)
* Generating active immunity against cancer antigens would promote immunological memory that would continuously detect and remove any emergent cancer cells (at the moment the treatments are passive and this means that the cancer could develop again at a later stage)
* Difficult to develop as cancer originates from ‘self’.
* Potential antigens are usually only weak antigens.
* Need to identify antigens that effectively only expressed by cancer cells.
* The key to bypassing immune tolerance and activating high levels of anti-tumour antibody or cytotoxic T cells lies in inducing CD4+ T-cell help.
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Cancer vaccines e.g., breast cancer vaccines
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**Summary IV**
* **Vaccines need to be affordable, stable, safe and induce immunological memory.**
* **Immunity achieved passively via preformed antibody - transient.**
* **Active immunity via infection or vaccination.**
* **Types of vaccines currently in use: live/attenuated, inactivated/killed or purified macromolecules (Toxoid, subunit, conjugate), recombinant vector vaccines and DNA vaccines**
* **Other vaccines in development include recombinant vectors and DNA vaccines.**
* **Vaccines can be used therapeutically as well as prophylactically.**
