vaccines

Question 1

father of vaccination

Answer 1

edward jenner
- used attenuated strain of cowpox – smallpox vaccine
- cross-reactivity between antibodies generated to cowpox that cross-react to smallpox

Question 2

challenge = ___

Answer 2

to test the efficacy of the vaccine by infecting individual with the virulent pathogen

Question 3

purpose of vaccination

Answer 3

• to induce the generation of long-lived memory T and B cells that protect against subsequent infection, without inducing disease
• herd immunity (provides protection to most susceptible members of a population)

Question 4

purpose of vaccination is to generate ___ pathogen-specific T and B cell memory responses

Answer 4

long-lived

Question 5

broad spectrum vaccines require ___, which means…

Answer 5

multivalency
carries more than one antigen from the pathogen in the vaccine

Question 6

___ promote immune responses to weakly immunogenic substances
mostly though…

Answer 6

adjuvants
maturation of DC’s

Question 7

features of effective vaccines

Answer 7

safe
protective, sustained protection
induces neutralizing antibody
induces protective T cells
low cost, few side-effects

Question 8

list the 4 types of vaccines approved for human use

Answer 8

1- live attenuated
2- killed
3- acellular
4- polysaccharide conjugate

Question 9

define live attenuated vaccine

Answer 9

attenuated pathogens that exhibit no pathogenicity but induce protective immunity
- ex: influenza virus- flu mist ; BCG- tuberculosis

Question 10

define killed vaccine

Answer 10

inactivated pathogens that still induce protective immunity
- ex: B. pertussis, polio virus, influenza virus

Question 11

define acellular vaccine

Answer 11

recombinant proteins, subunits- have certain subunits of pathogen
- ex: Hepatitis B

Question 12

define polysaccharide conjugate vaccine

Answer 12

linked protein carrier and polysaccharide
- isolate polysaccharides from bacteria, couple with protein carrier- conjugate
- ex: H. Influenzae, S. pneumoniae

Question 13

pros and cons of live attenuated vaccines

Answer 13

pros:
- strong immune response generating pathogen-specific T and B cells
- long-lived immunity
- single dose required

cons:
- danger of reversion to virulence
- rare reactions
- cannot be used in immunocompromised individual
- may not be stable under all storage conditions
- expensive

Question 14

name a more targeted approach to live attenuated vaccines

Answer 14

know sequence of the viral genome, focus on genes that cause virulence and mutate/delete them –> immunize patient with attenuated strain

Question 15

name pros and cons of killed vaccines

Answer 15

pros:
- safe and stable - not possible of reversion

cons:
- multiple doses required
- short lived protection
- limited CD8+ T cell activation
- generally less effective at eliciting protective immunity

Question 16

describe acellular (subunit) vaccination

Answer 16

• nonpathogenic, easily manipulated, stable
• requires adjuvant and knowledge of protective antigens
• requires multiple doses
• multivalency a requirement for broad protection

Question 17

what is an adjuvant

Answer 17

• agents added to vaccine formulations that enhance the immunogenicity of antigens in vivo
• 2 types: immunopotentiators and delivery systems
  . immunopotentiators often trigger TLR
  . delivery systems serve to prolong the duration of antigen exposure, “antigen depot”

Question 18

why are adjuvants required in many acellular vaccine formulations

Answer 18

• b/c stimulation of the adaptive immune system without linked activation of the innate response tends to elicit limited immunity
• b/c recombinant proteins may not fold correctly to induce pathogen-specific antibody responses
• b/c antigen administered without adjuvant may cause autoimmunity

Question 19

example of an adjuvant

Answer 19

Alum
- aluminum salts
- induces DC maturation
. the PRR: NLRP3 targets the inflammasome
. low-level inflammation

Question 20

what is the benefit of polysaccharide-protein conjugate vaccines?

Answer 20

conjugate vaccines rely on linked recognition
- B cell binds polysaccharide epitope linked to tetanus toxoid protein
- antigen internalized and processed
- peptides from protein component presented to T cell
- activated B cell produces antibody against polysaccharide antigen on the surface of the bacterium

Question 21

describe recombinant vectors

Answer 21

engineered microorganisms that carry genes from infectious agents
- adenovirus- used in HIV vaccine trials
- S. typhimurium

Question 22

recombinant vectors pros and cons

Answer 22

pros:
- single dose
- induced cell-mediated responses

cons:
- possibility of reversion
- vaccine complications

Question 23

name 3 types of experimental vaccines

Answer 23

1- cell-based: been used with cancers, grow patients DC’s in culture, load with antigens of choice, re-administer to patient - prime T cells to recognize tumor antigens

2- DNA: encodes protein antigens

3- viral or bacterial vectors: microorganisms that carry heterologous antigens

Question 24

challenges for vaccine development

Answer 24

• most vaccines elicit strong antibody responses
  . circulating neutralizing antibodies prevents systemic spread of pathogens
• but few elicit good CD8+ CTL responses

Question 25

how does a vaccine become approved for use in humans?

Answer 25

pre-clinical phase - in animals
phase 1 - safety testing, side effects measured in people
phase 2- more people given, “proof of concept phase”
phase 3- large scale administration, safe to FDA