vaccines Flashcards
father of vaccination
edward jenner
- used attenuated strain of cowpox – smallpox vaccine
- cross-reactivity between antibodies generated to cowpox that cross-react to smallpox
challenge = ___
to test the efficacy of the vaccine by infecting individual with the virulent pathogen
purpose of vaccination
- 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)
purpose of vaccination is to generate ___ pathogen-specific T and B cell memory responses
long-lived
broad spectrum vaccines require ___, which means…
multivalency
carries more than one antigen from the pathogen in the vaccine
___ promote immune responses to weakly immunogenic substances
mostly though…
adjuvants
maturation of DC’s
features of effective vaccines
safe
protective, sustained protection
induces neutralizing antibody
induces protective T cells
low cost, few side-effects
list the 4 types of vaccines approved for human use
1- live attenuated
2- killed
3- acellular
4- polysaccharide conjugate
define live attenuated vaccine
attenuated pathogens that exhibit no pathogenicity but induce protective immunity
- ex: influenza virus- flu mist ; BCG- tuberculosis
define killed vaccine
inactivated pathogens that still induce protective immunity
- ex: B. pertussis, polio virus, influenza virus
define acellular vaccine
recombinant proteins, subunits- have certain subunits of pathogen
- ex: Hepatitis B
define polysaccharide conjugate vaccine
linked protein carrier and polysaccharide
- isolate polysaccharides from bacteria, couple with protein carrier- conjugate
- ex: H. Influenzae, S. pneumoniae
pros and cons of live attenuated vaccines
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
name a more targeted approach to live attenuated vaccines
know sequence of the viral genome, focus on genes that cause virulence and mutate/delete them –> immunize patient with attenuated strain
name pros and cons of killed vaccines
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
describe acellular (subunit) vaccination
- nonpathogenic, easily manipulated, stable
- requires adjuvant and knowledge of protective antigens
- requires multiple doses
- multivalency a requirement for broad protection
what is an adjuvant
- 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”
why are adjuvants required in many acellular vaccine formulations
- 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
example of an adjuvant
Alum
- aluminum salts
- induces DC maturation
. the PRR: NLRP3 targets the inflammasome
. low-level inflammation
what is the benefit of polysaccharide-protein conjugate vaccines?
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
describe recombinant vectors
engineered microorganisms that carry genes from infectious agents
- adenovirus- used in HIV vaccine trials
- S. typhimurium
recombinant vectors pros and cons
pros:
- single dose
- induced cell-mediated responses
cons:
- possibility of reversion
- vaccine complications
name 3 types of experimental vaccines
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
challenges for vaccine development
- most vaccines elicit strong antibody responses
. circulating neutralizing antibodies prevents systemic spread of pathogens - but few elicit good CD8+ CTL responses
how does a vaccine become approved for use in humans?
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
