Samenvatting
Summary Gastles Vaccine Adjuvants - Di Pasquale
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Een complete, gedetailleerde, Engelstalige samenvatting over de gastles van professor Di Pasquale in verband met vaccine adjuvants.
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VACCINE TECHNOLOGY: VACCINEADJUVANTS – GUEST LECTURE DI
PASQUALE
ADJUVANT DEFINITION AND HISTORY OF DEVELOPMENT
KEY COMPONENTS OF VACCINES
1. Antigen(s)
a. Specificity of the immune response
2. Intrinsic immune defense triggers – or – adjuvants
a. Intended to enhance & modulate the IR to
vaccine antigen
b. Adjuvants = external immune defense triggers
WHAT IS AN ADJUVANT?
ADJUVANT = Substances that are intended to enhance relevant immune responses and subsequent
clinical efficacy of vaccines
VACCINE ADJUVANT = A component that potentiates the IRs to an antigen and/or modulates it
towards the desired immune responses
So it will enhance + modulate the IR that is elicited by the vaccine-Ag
HISTORICAL POINT OF VIEW
RAMON: chance and necessity (veterinary doctor)
1. Spontaneous abscesses at an injection site increase serum antitoxin titres
2. Attributed to ‘banal germs of the skin’
3. Substances able to induce sterile abscesses also produced enhanced anti-toxin response
a. These were called ‘adjuvants’ ~ ‘to help’
ALUMINIUM SALTS: aluminum precipitation enhances Ab-responses against diphtheria toxoid in
guinea pigs later on also seen in humans!
1
,STRATEGIES TO ADDRESS CHALLENGES IN VACCINE DEVELOPMENT
CHALLENGES:
1. Pathogens or diseases
a. When you want to develop a vaccine, you
look at the pathogen & the disease it causes
(difficult for parasitic diseases like malaria)
b. Big triad: HIV, malaria, TB these are a real
challenge for vaccine development
2. Populations
a. You also look at the populations based on
the characteristics of the pathogen and
disease and the type of Ag we have to
develop, there might be need for an adjuvant
We have population and pathogen challenges
Adjuvants must
o Be compatible with the vaccine’s Ag
o Be tailored one that is targeted to the right population: infants, elderly,…
WHY DO WE NEED ADJUVANTS? – CHALLENGES FOR VACCINES
1. Enhance immune response
a. Because we have challenging populations, with impaired IRs
2. Prolong immune response
a. Because now there are also vaccines that need booster vaccination it would be
better if we could avoid this need!
3. Overcome weak immunogenicity
a. Recombinant antigens with low immunogenicity
4. Induce a high and broad response
a. Because pathogens induce a broad, complex immune response
5. Reduce antigen dose needed
a. Supply problems caused by Ag-shortage are real!
b. Also Ag is difficult + expensive to make adjuvants are often cheaper and easier to
put into the vaccine this way we need less Ag
2
, UNDERSTANDING THE ROLE OF ADJUVANTS
Some antigens need help: why and when?
Not all vaccines need adjuvants, but all of them DO need something immune-triggering
We want to induce adapted immunity, not natural
NATIVE VIRUS
- The more we do with the native virus: the more we touch it/ inactivate it/ refine into purified
proteins the more we lose intrinsic immune-defensive triggers that are needed to activate
an IR = we increase the tolerability (the host wont react that strongly to it, but we want an
IR!) higher tolerability = no local and systemic effect + also less immunogenicity because
the IS must be alerted to action
- In this case an adjuvant can be beneficial!
- Native virus replication = life attenuated : usually don’t use this as adjuvants it still has
all the virological features that activate the IR you loose these features when you
inactivate the virus by purification: lose immunogenicity = increase tolerability
If we add adjuvant, we can increase immunogenicity, while controlling tolerability because
we DON’T want to lose safety!
Adjuvants are used to find balance between the safety & immunogenicity
SELECTING FROM NATURE: RIGHT AG AND WELL CHARACTERIZED ADJUVANTS
- Vaccine Ags alone sometimes too clean to elicit good immunogenicity
- Some selected adjuvants act as substitutes for natural immune-defense signals, enhancing
& directing the IR
o These are present in a pathogen (membrane, lipid part, DNA/RNA,…): these
components are innate-intrinsic antigens: if you don’t have these, then we need to
add something else (adjuvants = as replacement for innate-intrinsic antigens)
Presence of foreign DNA of bacteria/viruses or the presence of lipidic membrane that is ‘not
self’
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