WEEK 10: VACCINATIONS Flashcards
(117 cards)
1
Q
The first major barrier to infectious agents is…..
A
Skin
2
Q
Apart from skin, the next main barrier to infectious agents is ….
A
- Chemical barriers e.g. lysozyme in tears (targets peptidogylcans)
3
Q
The final way to control infectious agents is _____ which is composed of three main types of cell:
- _____
- ____
- _____
A
- Immune system
1. Leukocytes
2. DCs –> APCs
3. Adaptive cells
4
Q
What does Th1 promote?
A
- Macrophage activity
5
Q
What dos Th2 help with?
A
- Isotpye switching of Igs
6
Q
What does Th17 help with?
A
- Recruiting cells to the infection site
7
Q
Which Th cell is good for EXTRACELLULAR pathogens?
A
- Th17
8
Q
Which Th cell is good for INTRACDELLULAR pathogens?
A
- Th1
9
Q
What does it mean mean if the R0 is HIGH in terms of vaccine coverage to achieve control/eradication?
A
- Vaccine coverage (and efficacy) must be HIGH to achieve control eradication
10
Q
Which two diseases have high R0s?
A
- Measles and Pertussis (both 92-95%)
11
Q
What does herd immunity only apply for?
A
- Diseases that are spread from human-human (e.g. polio, measles)
12
Q
What does herd immunity reduce?
A
- The available pathogen reservoir for further infection
13
Q
In HIV does the reverse transcriptase have a proofreading function?
A
- NO
14
Q
Does HIV-1 undergo extremely rapid rates of mutation?
A
- YES
15
Q
Does the HIV-1 virus generate incredible diversity in the population AND within the individual?
A
- YES
16
Q
What is the most abundant antigen on the HIV virus surface?
A
- Env –> mutates at incredibly high rate
17
Q
In the HIV virus, do certain sites on Env have to be conserved to enable the virus binding and entry into the cells?
A
- YES
- CD4 binding site is conserved
18
Q
Can HIV be treated by passive immunisation?
A
- YES
- Make antibodies for the CD4 binding site that neutralise array of HIV-1 viruses
19
Q
In the HIV-1 virus vaccination, what can we use as the antigen?
A
- The CD4 binding site alone as the antigen (focus the immune response on the CD4 binding site)
20
Q
What was the smallpox vaccination based on?
A
- That milkmaids has nice skin and didn’t get smallpox BUT did get cowpox –> vacca–> cow in latin
21
Q
When was vaccination formally tested by Edward Jenner in?
A
- 1796
22
Q
What did Edward Jenner do in terms of Smallpox?
A
- took cowpox from milkmaid
- Inoculated arm of kid
- Kid was protected from variolation and smallpox
23
Q
For pertussis is the acellular vaccine a subunit vaccine or a inactivated vaccine?
A
Subunit vaccine
24
Q
Is the whole cell pertussis vaccine a subiunit vaccine or an inactivated vaccine?
A
Inactivated vaccine
25
What type of vaccine is DTaP and which vaccine class does it belong to?
- Toxoid vaccine
| - Part of the subunit vaccine class
26
Do live attenuated vaccines need additional adjuvants?
- NO
| - Because they are live, whole viruses or bacteria they INTRINSICALLY contain or generate a number of 'danger' signals
27
What is the format of live attenuated vaccines?
Models"real infection" with replciation, multiple antigens, and adjuvant signals
28
What are the pros of live attenuated vaccines?
- Induces strong, lifelong immunity for antibody and T cells (vaccina)
29
What are the cons of live attenuated vaccines?
- Can cause more severe side-effects (vaccina)
- Can cause disease in immunocompromised people (BCG-TB vaccine)
- Chance of reversion of virulence (tOPV-polio vaccine)
30
What is the format of the killed and inactivated vaccine?
Multiple antigens and adjuvant sigals
31
What are the pros of killed inactivated viruses?
- Can induce strong, long lasting immunity
32
What are the cons of killed inactivated viruses?
- Reliant on effective inactivation (historical accidents)
| - Can be more reactogenic (DTwP)
33
What is the format of subunit vaccines?
- Reduced selection of antigens and adjuvant signals
34
What are the pros of subunit vaccines?
- Very safe
| - Can induce antibody immunity
35
What are the cons of subunit vaccines?
- Not good for T cell immunity
- Immunity may wane or be less effective at preventing infection
- Requires multiple shots (DTaP)
36
What are needle free vaccines?
- Thousands of microscopic projections dry coated with live or subunit vaccines
- Applied to skin and penetrate to where immune cells reside
- NO refrigeration!
- Effective in animal trial
37
What does immunological memory require? (3 things)
- Innate immune responses
- Antigen uptake and presentation to trigger
- Adaptive immune responses (B and T cells)
38
What does vaccination and immunological memory INCREASE?
-Increases the NUMBER of memory B or T cells that recognise a specific antigen (on specific pathogen)
39
What does vaccination and immunological memory DECREASE?
-Amount of signal needed to activate antigen-specific memory B and T cells
40
what is passive immunity and give examples? (when is it given, what is it, what duration does it have?)
- Transfer of Ig from an immune --> non-immune individual/organism
- Ideally given BEFORE infection (otherwise won’t develop memory)
- IMMEDIATE onset of protection
- LIMITED DURATION (months, Ig turnover)
e. g. Maternal antibodies (Placenta IgM or colostrum in breast milk, also treatment for HIV-1)
41
What is active immunity and give example? (duration, when is it given, what is it?)
- Generated by the host
- Induction of a specific, protective immune response by EXPOSURE to antigen (i.e. vaccination)
- Must be give WELL IN ADVANCE of infection
- Protective immune response takes WEEKS to develop
- PROTRACTED DURATION (years, eventual turnover of memory B and T cells)
e. g. Vaccination, microbial infection
42
What is passive immunity good for?
- Toxins--> snake bite, tetanus, rabies, gas gangrene
- Outbreaks where antibody can provide protection to survivors BUT vaccines are not developed
- E.g. Performed during Ebola outbreaks
- Transfer serum from survivors (containing Ig) to individuals exposed to virus
43
What is active immunty good for? (with examples)
- Inducing WIDESPREAD immunity in the community to HIGHLY transmissible diseases
- Influenza, measles, HPV (Human Papolloma Virus)
44
What is the main aim of vaccination?
- Erdadication of disease from population
45
What are the three smaller aims of vaccination?
- Prevention of infection --> "efficacy" of the vaccine
- Reduce the infection load/severity (vaccinated people less likely to need hospitalisation)
- Reduce infection transmission (fewer people are infected at the population level)
46
What two things does herd immuntiy do?
- Limits the availability of the pathogen to infect and spread within a population
- Protects those who can’t be vaccinated (“community immunity”)
47
Do vaccines work well on old people?
-NO
48
What is the proper definition of herd immunity?
-Indirect protection from infection provided by the collective level of immunity within a population
49
What is herd immunity good for? (2 things)
- Decreasing transmission and burden of a disease
- Protecting individuals who are more vulnerable to infection (neonates, elderly, pregnant) or can’t be vaccinated (immunocompromised-cancer or Chron’s
50
What do transmission dynamics depend on?
- How infectious the pathogen is (R0)
- Frequency of
o Infected individuals (reservoir)
o Vaccinated individuals who develop protective immunity
o Vaccinated individuals who don’t develop protective immunity (vaccine efficacy)
o Individuals who can’t be vaccinated and unvaccinated individuals (vaccine coverage)
51
What does it mean if R0 is high?
Vaccine coverage and efficacy must be HIGH to achieve control/eradication
52
What are two factors that influence herd immunity?
- Environmental (i.e. crowded versus not crowded)
| - Infectivity of disease, rate of spread
53
What is the R0 for measles and what does this mean?
- 12-18
| - This means that it is VERY infectious
54
Is the MMR vaccine (measles) very efficacious?
- YES
| - 97% with 2 doses
55
For measles, what does the vaccine coverage have to be for outbreaks NOT to occur?
- 92-95%
| - Otherwise outbreaks will occur like in 1990
56
In terms of the measles outbreaks, what had a significant effect on controlling the outbreaks?
- Public health drives to increase vaccine coverage
| - This controlled outbreaks in 1993 and 2015
57
Can travel cause measles to spread from country-country?
- YES
58
Is it good to have a vacination strategy that is global?
- YES!
| - Because travel can spread infectious diseases
59
What are the two components to a vaccine?
- Adjuvant and Antigen
60
What is an adjuvant?
Compound that triggers innate immunity --> “The Danger Signal” --> triggers immunogenicity
61
What is an antigen?
Component of the virus that is immunogenic --> the ID tag
62
With vaccines, what are two important considerations when designing one?
- The ROUTE of infection and the TROPISM (ability of the pathogen to infect a given area) of the pathogen
63
What are the criteria for selecting a suitable antigen that is abundantly expressed and accessible to protective immune mechanisms?
- Expressed on the pathogen surface or secreted in toxin if antibody-mediated immunity provides protection
- Expressed on the surface of infected cells if T cell-mediated immunity provides protection
64
What are the criteria for selecting a suitable antigen that does not vary?
- Some pathogens can mutate antigens if immune responses are directed against those antigens (HIV, influenza, etc)
- Some pathogens change antigens during their natural life cycle (malaria, TB)
- Choose antigen which is ESSENTIAL TO CRITICAL LIFE STAGES OF THE PATHOGEN
65
What is the HIV immunogen problem?
- That HIV virus changes rapidly so it is hard to design vaccines against it
66
What must be conserved to allow the HIV virus to bind?
- Env-->Cd4 binding site
67
What is an example of passive immunity in the treatment of HIV?
- We can make Igs for the CD4 binding site--> neutralises a diverse array of HIV viruses
68
Where is the word adjuvant derived from?
- The latin word "adjuvare" --> to help
| - Adjuvant is anything that augments the body's immune response to an antigen
69
What does an adjuvant SPECIFICALLY do?
- Increases the MAGNITUDE of the ADAPTIVE IMMUNE RESPONSE
| - Shapes the TYPE of adaptive immune response (e.g. Antibody isotype, CD4+ T cells, CD8T cells)
70
What are two main ways that adjuvants augment the immune response?
1) Trigger innate immunity
| 2) Promote uptake of antigen by DCs
71
What are the specifics that occur in triggering innate immunity (adjuvants)?
- PRRs bind to PAMPs (viral or bacterial products OR cellular stress and damage (DAMPs)
- Can use PAMPs or INDUCE these DAMPs to act as vaccine adjuvant
- Each PAMP/DAMP elicits different set of INNATE cytokines which acts on B and T cells to skew immune system in different directions i.e. IL-12 + IFN-gamma = IgG2a antibody, Th1 CD4 T cells and CD8 T cells
72
Which PAMP or DAMP is Alum (adjuvant) associated wiht, which PRRs are targeted, and what type of immune response results?
- Cell stress (cell death/stress)
- Inflammasome PRRs targeted
- Antibody response occurs
73
Which PAMP/DAMP is MPL (Monophosphoryl Lipid A) associated with, which PRRs does it target, and which type of immune response does this result in?
- LPS (PAMP)
- PRR targeted is TLR-4
- Also results in antibody response
74
What is SPECIFICALLY involved in promoting antigen uptake?
INNATE CYTOKINES:
-Promotes the migration of DCs to vaccine site
Activate DCs which can increase their:
-Uptake of antigen
-Migration to the lymph node
-Expression of costimulatory molecules
Can also DIRECTLY promote the uptake of antigen by DCs:
-Make the antigen into a particle (Promotes phagocytosis)
-Promote the degradation of antigen in DCs
75
How can you directly promote antigen uptake by DCs in terms of adjuvants?
- Make the antigen into a particle (Promotes phagocytosis)
| - Promote the degradation of antigen in DCs
76
What are the adjuvants that promote antigen uptake whilst triggering innate immunity?
- Liposomes
- QuilA
(Also Alum and the HepB virus surface antigen)
77
What are the qualaities, mechanism, and type of immune response associated with liposomes (adjuvant trigering antigen uptake) ? (respectively)
- Small particles
- Antigen is loaded onto or into liposomes
- Antibody AND T cell response generated
78
What are the qualaities, mechanism, and type of immune response associated with QuilA (adjuvant trigering antigen uptake) ? (respectively)
- Forms pores in endosome membrane
- Antigen is released from endosomes into cytosol to promote degradation
- Antibody and T cell response (Th1 and Th17)
79
Can combining adjuvants result in an effect that is bigger than each of them individually?
- YES!
| - E.g. Malaria and Shingles combines Liposomes, MPL and QuilA
80
What will the optimal vaccine have in terms of safety?
- Minimal or acceptable side effects
81
What will the optimal vaccine have in terms of immunological mechanisms?
- Induce a protective immune response
- High vaccine efficacy rates
- Durable protection (stable immune memory)
82
What will the optimal vaccine have in terms of logistics?
- Single dose (difficult to ensure repeat doses)
- Stable (must be able to be stored and shipped preferably without “cold chain”)
- Non-invasive administration (oral, inhaled, etc.--> but not always possible because of tropism)
- Low cost (e.g. the measles vaccine is US $1)
83
What are the different phases for testing of vaccines?
Phase I: Safety
Phase II: Immunogenicity (and Safety)
Phase III: Immunogenicity, feasibility (and Safety)
Phase IV: Post approval monitoring (i.e. Safety)
84
What occurs in phase I Safety?
- Small, very controlled study to determine if any adverse events are observed
- May collect preliminary immunogenicity data
85
What occurs in phase II: Immunogenicity (and Safety) for vaccine design?
-Small study to test if the vaccine can protect from infection in a target population (at risk of infection)
86
What occurs in phase IV: Post approval monitoring (i.e. Safety) for vaccine design ?
-Monitor adverse events in vaccinated population and the strain of circulating pathogen (does it mutate?)-->longitudinal study
87
What occurs in phase III: Immunogenicity, feasibility (and Safety) for vaccine design?
-Large study to validate that vaccine has protective effect in general population
88
What are 4 types of vaccine side effects?
- Swelling at vaccine site, fever, muscle aches, fatigue:
- Anaphylaxis:
- Seizures in children:
- Guillian-Barre Syndrome:
89
What are the three classes of vaccines?
- Live attenuated vaccines
- Killed inactivated vaccines
- Subunit vaccines
90
What do live attenuated vaccines do? (also what are two examples of them)
- Uses the pathogen or a closely related organism
- Organism is the ATTENUATED --> passage through the cell culture or use of genetic techniques to induce mutations that REMOVE VIRULENCE but RETAIN IMMUNOGENICITY
- e.g. Smallpox, Polio
91
What do killed inactivated vaccines do and what are two examples of viruses?
- Uses chemical (formalin or phenol treatment) or heat inactivation to kill pathogen, which is then used in the vaccine, sometimes with an additional adjuvant
- e.g. Polio (as well), Pertusis
92
What do subunit vaccines do and what is an example of a virus?
- Uses selected purified antigens in COMBO. With selected adjuvants to TRIGGER INNATE immunity, promote antigen uptake and induce the appropriate adaptive response
e. g. Pertusis
93
In terms of smallpox, what is variolation and was this effective?
Dead puscle skin was ground up and inhaled …..BUT 1-2% died --> Can have a “skin inoculation” (cut skin and apply material) or “Nasal insnufflation” (Sniff material up nose)
94
When was smallpox eradicated?
-December 1979 (only human disease to be completely eradicated)
95
Why was Smallpox successfully eradicated?
- Stable, cheap and VERY EFFICACIOUS (90-97%)
- Reservoir was limited--> Only infects humans (no animals), Infection died or resolved infection (no chronic infection), Infection was EASILY recognised (isolate the infected), Only 2 viral variants (Variola major and variola minor), Intensive, co-ordinated, global surveillance-ring vaccination.
96
Can the live vaccine cause SEVERE SIDE EFFECTS and can it be given to the immunocompromised?
- YES!
| - Also can’t be given to immunocompromised
97
What are the examples of the live vaccines?
- Polio and smallpox
98
What are the examples of the inactivated vaccines?
- Also Polio and Pertussis
99
What are the examples of the Subunit vaccines?
- Pertussis
100
What is polio? (poliomyelitis) (mode of transmission, symptoms, mortality rate)
- Highly infectious viral infection caused by 3 strains (1,2,3)
- Fecal-oral transmission and invades nervous system
- Can cause RAPID paralysis
- 5-10% mortality rate
101
What is the trivalent oral polio vaccine (tOPV)? (who was it developed by and when, what type of vaccine is it, what is it effective at inducing, what is route of admission, what is bad about it)
- Developed by Albert Sabin (1963)
- Live attenuated vaccine (3 strains)
- VERY EFFECTIVE at inducing immunity
- Easy to administer (oral)
- But it can-->Revert to virulent virus
- Cause vaccine-induced paralysis
102
What is information about the trivalent INACTIVATED polio vaccine? (who developed it, what inactivates it, what is route of admission)
- Developed by Jonas Salk (1955)
- Inactivated vaccine (3 strains)
- Virus is FORMALIN inactivated
- Not as effective at inducing immunity (bc. virus is inactive and can’t replicate)
- Have to INJECT the vaccine
103
What is the cutter indicident (1955)?
- In relation to the polio vaccine for the inactivated virus
- Cutter labs did NOT effectively inactivate the polio virus
- 56 paralysed and 5 dead
- Turned into an epidemic
- This incident made it clear that VACCINE SAFETY MUST BE PROMINENT!!!!
104
What is information about pertussis?
- Very infectious
- Respiratory infection caused by Bordatella pertussis
- Bacteria colonises the host and produces a toxin --> cough
- Severe in small children and FATAL in infants (0.8%)
105
What is the DTwP vaccine? (older vaccine)
- Formulated with diphtheria and tetanus toxin
- Inactivated vaccine
- Treat bacteria with formalin--> inactivates the bacteria and toxin
- Adjuvanted with alum--> Good at inducing Ig responses
- ISSUES WITH REACTOGENICITY--> High rate of fevers and seizures
106
What is the 'new' DTaP vaccine?
- New vaccine known as the “acellular” vaccine (DTaP)
- Contains 3-5 purified pertussis antigens including inactivated toxin
- Has ALUM adjuvant
- Much less reactogenic BUT immunity is LESS EFFECTIVE and WANES quickly so adolescent boost (TdaP) was added
107
What are the different types of subunit vaccines?
- Acellular vaccines
- Recombinant vaccines
- toxoid vaccines
108
What is involved in acellular vaccines? (subunit vaccines)
- Culture your pathogen and purify out required antigens
| - But if your pathogen is difficult and dangerous to grow seek out other vaccine types
109
What is invovled in the recombinant vaccine? (subunit vaccines)
- Identify antigen of interest
- Clone the gene coding that antigen into expression system that grows, produces protein at high rate (i.e. yeast)
- Purify the protein antigen
110
What is involved in toxoid vaccines (subunit vaccine class)?
- Aim is to induce antibody that NEUTRAISES toxin made by the pathogen that causes disease (before it causes disease) NOT necessarily the pathogen itself
- Purify and inactivate toxins to use as antigens
- i.e. Diphtheria, tetanus and pertussis (DTaP vaccine)
111
What does the polysaccharide only vaccine do and what are some down sides about it cmpared to the conjugate polysaccharide to immunogenic protein?
- Bacterial capsules made of polysaccharide are targets for antibody
- But polysaccharide is NOT immunogenic for T cells
- Polysaccharide only vaccines LACK CD4T cell help for B cell responses and immunity is WEAK and SHORT LIVED
112
What is good about the Conjugate polysaccharide to immunogenic protein (i.e.toxoid) and what are examples of diseases where this vaccine has been applied?
- CD4 T cell response to protein provides “help” for the B cell response to the polysaccharide
- i.e. Meningococcal or Haemophillus influenzae B vaccines
113
What are the 3 aims of vaccines in the future?
1. Safety--> Maintain MINIMAL side effects
2. Immunological--> Increase POTENCY, increase the MAGNITUDE of the immune response, TAILOR the type of immune response
3. Logistical --> Make vaccines EASIER to administer and make them CHEAPER to administer
114
What are viral vector vaccines?
-Take the harmful pathogen--> Identify gene for target antigen
-Take minimally pathogenic virus --> Remove genetic material associated with virulence --> insert target antigen
It infects the cells like a vector virus--> not virulent and expresses the target antigen
115
What is information about the Ebola virus?
- Viral hemorrhagic fever (symptoms caused by loss of epithelial integrity, vascular walls become leaky)
- 2014-16 epidemic in Liberia and other places
- Needed vaccine that had antibody and T cell immunity directed against Ebola GLYCOPROTEIN (GP)
116
What is information about the Recombinant VSV (Vesicular stomatitis virus) vector vaccine?
- VSV is the causative agent of foot and mouth disease
- If you remove the VSV GP gene:
- Viral vector can NOT replicate effectively
- Insert the Ebola GP gene:
- Viral vector induces ROBUST immunity to Ebola
117
What did the ring vaccination study prove in terms of Ebola?
- That the Ebola vaccine was 100% effective
| - But not accurate efficacy rate
