VACCINE TECHNOLOGY: ATTENUATED
VACCINES
1: LIVE VACCINES
- Live vaccines = consist of viruses/bacteria that replicate to a limited degree in the host
o Resembling that of the natural microorganism
o Eliciting an IR similar to that elicited by the natural infection = GOOD!
- Attenuation: disease-causing capacity reduced by biological/technical manipulations
o Attenuation needs to be balanced!
Overattenuated: no longer infectious enough to function as vaccine, no IR
will be induced
Underattenuated: retaining pathogenicity even to a limited extend (chance
of disease)
o Sometimes attenuation does not work if the pathogen is already causing a weak
IR!
- Live vaccines usually elicit:
o Humoral immunity Abs
o Cellular immunity cytotoxic T-lymphocytes (CTLs)
o = strong!!
- Some live vaccines are close to ideal in their capability to elicit life-long protection, in just 1-2
doses, with minimal reactogenicity
- Live vaccines may be feasible in cases in which the natural infection/disease confers life-
long protection in the host
o So if life-long protection is possible after natural infection, it is possible to make live
vaccines: when a natural infection does not give good protection by itself no
suitable for making attenuated vaccines!
IMPORTANT TABLE: EXAM!
Live vaccines
MMR vaccines = Live-attenuated
vaccines that protect against
measles, mumps, rubella, (MMRV:
and varicella (chickenpox), only for
children who are 12 months
through 12 years of age).
Inactivated vaccines
1
, For live vaccines, safety is uncertain before large-scale use that is why post-market
surveillance is that important!
Nucleic acid-based vaccines
2: ATTENUATED VACCINES
2.1: WHEN IS DEVELOPING A LIVE, ATTENUATED VACCINE A GOOD OPTION?
- Strategic choice of developing live – inactivated – or nucleic-acid-based vaccine should take
into account:
o Pathogenesis – epidemiology – immunobiology of the target infection or disease
o Technical feasibility of alternative vaccine designs
- Epidemiology = target population for the vaccine
o Age + state of health of this population can favor certain designs as more appropriate
to elicit protective immunity
o A vaccine intended for healthy subjects (especially infants): minimizing acute
reactogenicity is CRITICALLY IMPORTANT as is minimizing the risk for chronic
autoimmune disease development in genetically susceptible subjects
The people are healthy, we want to keep it that way!
Don’t give live attenuated to an immunocompromised person!
2.2: WHEN IS LIVE-ATTENUATED VACCINE NOT A GOOD OPTION?
Live vaccines: not technically feasible for most vaccines currently under development
balance between over- and underattenuation is delicate and, for some viruses/bacteria,
technically unachievable right now
o Because a live vaccine can replicate is possible to revert to more natural,
pathogenic state
o Some live vaccines can be transmitted from a vaccinated to non-immunized person
Serious if the recipient has an immune deficiency! Live vaccines = not safe to
be used in immune deficient people
Allows for higher risk of reversal to virulence and cause of disease
- MAJOR ISSUE = SAFETY: adverse effects that happen in 1/10 000 people only becomes visible
in post-marketing surveillance!
2
VACCINES
1: LIVE VACCINES
- Live vaccines = consist of viruses/bacteria that replicate to a limited degree in the host
o Resembling that of the natural microorganism
o Eliciting an IR similar to that elicited by the natural infection = GOOD!
- Attenuation: disease-causing capacity reduced by biological/technical manipulations
o Attenuation needs to be balanced!
Overattenuated: no longer infectious enough to function as vaccine, no IR
will be induced
Underattenuated: retaining pathogenicity even to a limited extend (chance
of disease)
o Sometimes attenuation does not work if the pathogen is already causing a weak
IR!
- Live vaccines usually elicit:
o Humoral immunity Abs
o Cellular immunity cytotoxic T-lymphocytes (CTLs)
o = strong!!
- Some live vaccines are close to ideal in their capability to elicit life-long protection, in just 1-2
doses, with minimal reactogenicity
- Live vaccines may be feasible in cases in which the natural infection/disease confers life-
long protection in the host
o So if life-long protection is possible after natural infection, it is possible to make live
vaccines: when a natural infection does not give good protection by itself no
suitable for making attenuated vaccines!
IMPORTANT TABLE: EXAM!
Live vaccines
MMR vaccines = Live-attenuated
vaccines that protect against
measles, mumps, rubella, (MMRV:
and varicella (chickenpox), only for
children who are 12 months
through 12 years of age).
Inactivated vaccines
1
, For live vaccines, safety is uncertain before large-scale use that is why post-market
surveillance is that important!
Nucleic acid-based vaccines
2: ATTENUATED VACCINES
2.1: WHEN IS DEVELOPING A LIVE, ATTENUATED VACCINE A GOOD OPTION?
- Strategic choice of developing live – inactivated – or nucleic-acid-based vaccine should take
into account:
o Pathogenesis – epidemiology – immunobiology of the target infection or disease
o Technical feasibility of alternative vaccine designs
- Epidemiology = target population for the vaccine
o Age + state of health of this population can favor certain designs as more appropriate
to elicit protective immunity
o A vaccine intended for healthy subjects (especially infants): minimizing acute
reactogenicity is CRITICALLY IMPORTANT as is minimizing the risk for chronic
autoimmune disease development in genetically susceptible subjects
The people are healthy, we want to keep it that way!
Don’t give live attenuated to an immunocompromised person!
2.2: WHEN IS LIVE-ATTENUATED VACCINE NOT A GOOD OPTION?
Live vaccines: not technically feasible for most vaccines currently under development
balance between over- and underattenuation is delicate and, for some viruses/bacteria,
technically unachievable right now
o Because a live vaccine can replicate is possible to revert to more natural,
pathogenic state
o Some live vaccines can be transmitted from a vaccinated to non-immunized person
Serious if the recipient has an immune deficiency! Live vaccines = not safe to
be used in immune deficient people
Allows for higher risk of reversal to virulence and cause of disease
- MAJOR ISSUE = SAFETY: adverse effects that happen in 1/10 000 people only becomes visible
in post-marketing surveillance!
2
