Vaccines and Vaccination Flashcards
(50 cards)
1
Q
What is immunity?
A
- state of protection from a particular infectious disease
2
Q
What is immunization?
A
- process of producing a state of immunity in a subject
- deliberate induction of an immune response by exposing an individual to a specific antigen
- often called vaccination when used to induce a protective immune response to a microbial pathogen
3
Q
What is vaccination?
A
- deliberate induction of adaptive immunity to a pathogen by injecting dead/ attenuated (nonpathogenic) live form of pathogen or its antigens (vaccine)
- intentional administration of a harmless/ less harmful form of pathogen to induce a specific adaptive immune response that protects the individual against later exposure to the pathogen
4
Q
What is a vaccine?
A
- preparation of immunogenic material used to induce immunity against pathogenic organisms
5
Q
How can immunity be achieved?
A
- Passive Immunity > natural passive/ artificial passive
> recipient not making own antibodies so temporary - Active Immunity > natural active/ artificial active
> make own antibodies
6
Q
What are the 4 ways immunity can be achieved?
A
- Natural Passive > maternal placenta/ breast-feeding
- Artificial Passive > transfer of preformed antibodies (antiserum)
- Natural Active > infection/ recovery
- Artificial Active > immunization (vaccines)
7
Q
What is passive immunization?
A
- delivery of preformed antibody
- occurs naturally > maternal IgG crosses placenta to fetus/ IgA in breast milk
- can be achieved by injecting recipient with preformed antibodies (antiserum) from other immune individuals
8
Q
What is antiserum?
A
- fluid component of clotted blood from an immune individual
- contains antibodies against antigen used for immunization
9
Q
What conditions warrant the use of passive immunization?
A
- immune deficiency > individual can not make antibodies
- toxin/ venom exposure with immediate threat to life > not enough time to make antibodies
- exposure to pathogens that cause death faster than an effective immune response can develop
- protect travelers/ healthcare workers who experience exposure to pathogens they lack immunity for
10
Q
What are the risks associated with injection of preformed antibody?
(artificial passive immunity/ passive immunization)
A
- immune response to antibody > if Ab made in another species
> anti-isotype response
> has serious complications - immune response to antibody > if human gammaglobulin used
> anti-allotype response
> much less serious than anti-isotype response
11
Q
What is an anti-isotype response?
A
- immune response to injection of preformed antibody > antibody made in another species > serious complications
- production of IgE against horse-specific determinants
> IgE-horse antibody immune complexes induce mast cell degranulation > systemic anaphylaxis - production of IgG/ IgM antibodies specific for foreign antibody
12
Q
What has been a major impediment to monoclonal antibody therapy in humans?
A
- antibodies made by immunizing nonhuman species
- humans can develop antibody response against nonhuman antibodies
- leads to allergic reactions/ anaphylaxis
13
Q
How can antibodies be engineered to reduce their immunogenicity in humans?
A
Humanization
- process of making antibodies that are not recognized as foreign by immune system
14
Q
What are the suffix naming conventions to identify the type of antibody?
A
- omab > murine monoclonal antibodies (fully mouse)
- ximab > chimeric antibodies > entire variable region spliced into human constant regions
- zumab > humanized antibodies > murine hypervariable regions spliced into human antibody
- umab > derived entirely from human sequences (fully human)
15
Q
What was the first vaccine developed?
A
- Edward Jenner > inoculated with cowpox to prevent smallpox
16
Q
What is a primary vs secondary response?
A
- primary response > first encounter with antigen
> initial lag phase/ Ab levels plateau - secondary response > second exposure to same antigen
> very rapid/ intense antibody secretion (memory)
17
Q
What are some features of effective vaccines?
A
- must induce long-lasting protection while being safe/ inexpensive
18
Q
What are the 4 phases of vaccine clinical trials in humans?
A
Phase I > assess human safety > monitor small number of volunteers for adverse side effects
Phase II > effectiveness against pathogen is evaluated > test for measurable immune responses to immunogen > many vaccines fail at this stage
Phase III > expanded volunteer populations > natural evidence of protection against “real thing” is desired outcome
Phase IV > after marketing/ distribution > long-term impacts/ monitor safety and effectiveness (after vaccination)
19
Q
What is herd immunity/ how does it work?
A
- population scale immunity
- as a critical mass of people acquire immunity (either through vaccination/ recovery from infection) > they can serve as buffers for rest
- works by decreasing the # of individuals that can harbor/ spread the infectious agent > reduces chances that susceptible individuals will become infected (indirect protection)
20
Q
How many people must be vaccinated to prevent virus spread?
A
1-1/R0
R0- # of new infections generated by first infectious individual in a completely susceptible population
21
Q
What is the effective reproductive number?
A
RE- reflects # of new infected individuals per 1 infectious individual
- defined by product of R0/ proportion of population that is susceptible
22
Q
What is the herd immunity threshold?
A
- fraction of the population that is susceptible when RE falls below 1 and the # of infectious individuals peaks
23
Q
What are 8 different types of vaccines?
A
- live attenuated
- inactivated/ killed
- toxoid (inactivated exotoxin)
- subunit
- conjugate
- recombinant vector
- DNA vaccines
- RNA vaccines
24
Q
How are live attenuated vaccines made?
A
- microorganisms are attenuated (disabled) > lose ability to cause significant disease but retain capacity for slow/ transient growth within an inoculated host
- attenuation can be achieved by growing bacterium/ virus for prolonged periods under abnormal culture conditions
25
What are some pros/ cons of live attenuated vaccines?
Pros- more efficient production of highly effective memory cells > due to capacity for growth > prolongs exposure to epitopes on attenuated organisms
- promote both humoral/ cell-mediated response
Cons- may mutate/ revert to more virulent form > disease risk
- can be associated with complications like in natural disease
- may require cold chain for stability during transport
26
What is an example of a naturally attenuated agent?
- Vaccinia virus (cowpox) > unable to cause disease in host, while able to immunize against smallpox
27
How are viruses traditionally attenuated?
- by selecting for growth in nonhuman cells
- virus is isolated from patient/ grown in cultured human cells
- virus adapted to growth in different species > until grows only poorly in human cells (due to mutations)
- attenuated virus grows poorly in human host > produces immunity but not disease > can be used as vaccine
28
How can live-attenuated viruses be made safer?
- recombinant DNA technology
- identify gene in virus required for virulence but not growth/ immunogenicity > multiply mutate/ delete gene > create avirulent/ nonpathogenic virus that can be used as vaccine
29
What is the current approach/ ideal approach to vaccination against influenza?
- current approach > killed virus vaccine > reformulated annually based on prevalent virus strains
- ideal approach > attenuated live organism that matched prevalent virus strain
30
What is the problem with the killed virus current approach to vaccination against influenza?
- Antigenic shift- Influenza escapes original immune response (changes every year)
- Heterosubtypic immunity- weak protection from previous infections of different subtypes seen in adults but not children
31
What is an example of a live attenuated vaccine?
OPV- used for decades worldwide
- colonizes intestine > induces IgA/ IgM/ IgG production
- original form consists of 3 attenuated strains of poliovirus
- requires boosters (unlike other attenuated viruses) since 3 strains interfere with each other's replication
- first immunization > 1 strain predominates > induces immunity to strain
- second immunization > immunity by previous immunization limits growth of previously predominant strain > enables one of remaining 2 strains to colonize/ induce immunity
- third immunization > immunity to all 3 strains achieved
32
How are inactivated/ killed vaccines made?
- pathogen incapable of replication but still induces an immune response
- heated/ chemically treated to inactivate
> heat inactivation causes protein denaturation > alters epitopes
> chemical inactivation is more successful
33
What are some pros/ cons of inactivated/ killed vaccines?
Pros- no reversion to pathogenic form
- often more stable > ease of storage/ transport
Cons- often require booster shots
- less effective in inducing cell-mediated immunity (predominantly humoral)
- potentially dangerous if not all pathogen inactivated/ killed
34
What are subunit vaccines/ what are the 3 most common applications?
- use specific purified macromolecules derived from pathogen
> inactivated pathogen exotoxins (toxoids)
> isolated capsular polysaccharides/ surface glycoproteins
> purified key recombinant protein antigens
35
What is a limitation of subunit vaccines?
- especially in polysaccharide vaccines
- inability to activate TH cells
- activate B cells in T-independent manner > little class switching/ no affinity maturation/ little memory cell development
- can be avoided by conjugating polysaccharide antigen to protein carrier > TH response against both protein/ polysaccharide
36
What are toxoid vaccines?
- inactivated exotoxins induce anti-toxoid antibodies > bind to toxin/ neutralize its effects
37
What is the rationale for subunit vaccines consisting of capsular polysaccharides?
- antiphagocytic properties of polysaccharide capsules contributes to virulence of some bacteria
- vaccinations with capsular polysaccharides induce formation of opsonizing antibodies > enhance phagocytosis
38
How is DNA recombinant technology used in designing subunit vaccines?
- used to produce purified toxins
- used to produce surface viral/ bacterial/ protozoal antigens
- ex) Hepatitis B vaccine > clone gene for HBsAg > express in yeast cells > grow recombinant cells > allow HBsAg to accumulate/ harvest from yeast cells > release recombinant HBsAg
39
What are recombinant vector vaccines?
- genes that encode antigens of pathogens are introduced > attenuated viruses/ bacteria
- attenuated organism serves as vector > replicating within vaccinated host/ expressing gene it carries from pathogen
- ex)- foreign gene into vaccinia virus vector
40
What are some pros/ cons of recombinant vector vaccines?
Pros- prolong immunogen delivery/ encourage cell-mediated responses
- do not revert to pathogenic forms like live attenuated vaccines
Cons- stability issues
41
What are DNA vaccines?
- plasmid DNA injected directly into muscle of recipient
- DNA integrates > host chromosomal DNA
- aims to deliver DNA plasmid to APCs near injection area
42
How can immune responses to DNA vaccines be enhanced?
- booster shot with protein antigen > DNA prime/ protein boost strategy
- include supplementary DNA sequences in vector > genetic adjuvants
43
What are some pros/ cons of DNA vaccines?
Pros- induce both humoral/ cell-mediated immunity
- prolonged expression of antigen > enhances memory
- no refrigeration needed
- same plasmid vector can be engineered to insert DNA encoding a variety of proteins > simultaneous manufacture of DNA vaccines for different pathogens
Cons- still no DNA vaccines available
- usefulness to protect against infection disease is unknown
44
What is the major drawback of RNA vaccines?
- need to be stored at very low temperatures from production to time of use (relative instability) > increases cost of delivery
45
What are 2 ways vaccine immunogenicity can be improved?
- adding a conjugate (immunogenic protein)
- adding a multivalent compound (phospholipid > ISCOM/ liposome > to get intracellular)
46
What is an example of a conjugate used to improve vaccine immunogenicity?
- Hib vaccine- conjugate of bacterial surface polysaccharide (non-immunogenic)/ tetanus toxoid protein (highly immunogenic)
- boots B cell response > anti-polysaccharide antibodies
47
What is an example of a multivalent used to improve vaccine immunogenicity?
- incorporate membrane proteins from pathogens > ISCOMs/ liposomes > can deliver agents inside cells so mimic endogenous antigens > cell-mediated immunity
- serve as adjuvants
48
What is an adjuvant?
- any substance that enhances immune response to antigen to which it is mixed
49
Why is route of vaccination an important determinant of success?
- ideal vaccination induces host defences at point of entry of infectious agent > stimulation of mucosal immunity is important goal
- most vaccines given by injection > many disadvantages
50
What is an example of the impact route of vaccination has on success?
- intranasal vaccine against influenza > mucosal antibodies > more effective than systemic to control upper respiratory tract infection
- systemic antibodies from injection > more effective to control lower respiratory tract disease > major cause of mortality
