14 - Vaccine (Steph) Flashcards
what is a vaccine
pharmacological formulation which can stimulate the immune system and include a highly controlled and predictable immune response against a given (usually infectious) disease
purpose of a vaccine
Purpose is usually prophylaxis (= to prevent):
- provide relative or absolute immunity to a given disease for preventing at least
development of clinical signs of disease when exposed to the authentic agent
- should have short or better long-lasting effect, ideally life-long
- without inducing severe side effects or disease associated with agent
minimal components of a vaccine
specific component: antigen (immunogen)
Unspecific components: adjuvant, solvents, preservatives
what is an adjuvant
agent that costimulates the immune system and increases the response to a vaccine, without having any specific antigenic effect in itself (danger signals/damps)
what is the purpose of an adjuvant
accelerate, prolong, and enhance antigen-specific immune responses when used in combination with specific vaccine antigens
what should adjuvant trigger
innate immune system, DCs and T-cells
effects wanted from an adjuvant
- improve delivery adn uptake of Ag by APCs
- depot and slow release
- act as DAMP
-induce inflammation (recruit more APCs)
Types of adjuvant
Neutral liposomes, microspheres, mineral salts, cationic liposomes, ISCOM, water and oil emulsions, PRR Agonists
describe an anamnestic/secondary response (aka when you get a booster vaccine)
- much faster, much more efficient
- at least humoral, ideally
also (memory) T-cell component - amount of antibodies is surrogate marker
- (neutralizing Abs can be key)
ultimate goal of vaccines
Induction of immunological memory,
in form of antigen-specific memory cells
- humoral, plasma cells
- if possible, also effector T-cells, memory T-cells
why is herd immunity of less than 100% efficacy okay
- chain of infection is disrupted
- provides protection for individuals who cannot develop immunity
what is the minimum efficacy needed to achieve herd immunity
> 90% (85-95%)
what is the classical approach to immunization
Primary immunization
a) killed vaccine: 2-3 applications
2 times short (e.g. 0, 4 weeks)
3 rd long (6-12 months)
this is basic/primary immunization
booster every 3-5 (10) years
b) live vaccine, 1 shot might do it…
why do you need boosters
a) no good memory effect
b) agent changes all the time
c) (iatrogenic) non-responders
active vaccine
Killed: inactivated agent/toxin, or recombinant protein, vector vaccine
live: attenuated, replication competent but no major virulence
passive vaccine
application of immunoglobulin/hyper-immunoglobulin
pros of active vaccine
works immediately, also in immunosupressed individuals
cons of passive vaccine
only humoral immunity
only transiently (weeks/months)
side effects low (risk of anaphylaxis)
infection risk (blood products)
do active vaccines work immediately
no, they work after some delay
pros of a killed vaccine
compatibility good/easy to handle
may contain ‘toxic’ compounds (adjuvant!)
cons of killed vaccine
multiple applications needed
only/mainly humoral immunity
pros of a live vaccine
longtime protection (sometimes lifetime)
single application plus (few) booster
humoral and cellular immunity
cons of a live vaccine
danger of failure/infection (they have to replicate, cold chain,
revertants)
what conditions warrant delivery of preformed antibodies
– immune deficiency
– toxin or venom exposure with
immediate threat to life
– exposure to pathogens that can cause
death faster than an effective immune
response can develop (post-exposure,
PEP)
what can delivery of pre-formed antibodies lead to
type 1 or type 3 sensitivity
name some differnt types of vaccine
- live (attenuated)
- inactivated/killed
- toxoid
- subunit/component
- conjugate
- recombinant (vector)
- DNA
- mRNA (very new)
what is a live attenuated vaccine
weakened pathogens
pros of live attenuated vaccine
» retain their ability to replicate, promoting
both humoral and cell-mediated responses
» often do NOT need boosters
cons of live attenuated vaccine
- may mutate back (revert) to pathogenic
form - may have more side-effect complications
- may also require a “cold chain” for
stability during transport
Live attenuated vaccines
what are inactivated or killed vaccines
heated or chemically treated to inactivate
pros of inactivated/killed vaccine
- no reversion to pathogenic form
- often more stable/easy to store and transport
cons of inactivated or killed vaccines
» require booster shots
» don’t replicate in host, so often don’t induce cell-
mediated immunity (humoral mainly/only)
» adjuvants often required
» (potentially dangerous if not all pathogen is
killed/inactivated)
what are marker vaccines used for
only in vetmed, used to differentiate infected from vaccinated animals by using ELISA
what is the problem with marker vaccines
not 100% effective, mixture of vaccinated and infected animals possible; animals that spread the virus should be eliminated
what are subunit/component vaccines
purified macromolecules derived from antigen
– inactivated exotoxins/toxoids
– inactivated capsular polysaccharides
– inactivated surface glycoproteins (or recombinant
protein Ag)
– recombinantly expressed protein
pros of subunit/component vaccines
no reversion to pathogenic form
» often more stable/easy to store and transport
cons ofsubunit/component vaccines
require booster shots
» don’t replicate in host, so often don’t induce cell-
mediated immunity (humoral mainly/only)
» adjuvants often required
» (potentially dangerous if not all pathogen is
killed/inactivated)
what are recombinant vector vaccines
use unrelated vector to deliver part of pathogen (carry another pathogens genes and express them but no replication in host)
cons of recombinant vector vaccines
– Cons:
» some of the attenuated vaccine
problems are still present (especially
stability issues)
pros of recombinant vector vaccines
» some benefits of attenuated vaccines
» fewer risks―not using the actual
pathogen, but something else entirely
DNA vaccine
plasmids carrying pathogen genes injected into muscle tissues
- host cells take up DNA and express it internlly –> provides Ag presentation via MHC class I, stimulating CTL production
pros of DNA vaccine
» induces humoral and cell-mediated
immunity
» very stable and customizable
cons of DNA vaccine
has not worked well so far LOL
mRNA vaccines
synthetic mRNA encoding immunogenic proteins of pathogens, packaged in particles for delivery
How do mRNA vaccines work
Host cells take up mRNA delivered in particles and express it
internally
» provides Ag presentation via MHC class I, stimulating CTL production;
also MHC class II, targeting DCs
» mRNA immunogenicity, instability and inefficiency had to be
overcome
pros of mRNA vacciens
» induces humoral and cell-mediated immunity
» no infection context, can be easily adapted/changed
» very effective, very high response rates
cons of mRNA vaccines
stability issues (mostly overcome)
– duration of immune response likely as dead vaccines
conjugate or multivalent vaccines
some molecules aren’t
strong enough Ag on
their own to stimulate a
good response
(e.g. sugars!; B1 B cells)
* couple them with
something else (protein)
that is immunogenic
vaccination recommendations for cats and dogs
frequency of vaccination depends on lifestyle of the pet, and each individual pet vaccination plan is decided by owners at routine annual examinations
what are canine core vaccines and some exam
core vaccines are recommended for all dogs with unknown vaccination history. They are for diseases that have significant morbidity and mortality (distemper, adenovirus, rabies)
what are canine non-core vaccines
are optional and generally less effective (bortadella, leptospiria borellia)
what is important about feline vaccination guidelines
vaccine associated sarcomas are common so minimze frequency of vaccination in cat
what are some considerations to make if there are pre-existing antibodies when vaccinating
can interfere with vaccinations, in particular with live vaccines
side effects of vaccinations
redness, swelliing, pain injection area, elevated temperature, common cold, muscle pain
rate of unwanted adverse effects of vaccines
1:2,000,000 vaccinations
why was measles not eliminated
- failure to immunize enough
- importation of measles
what are features of an effective vacccine
safe: vaccine itself must not cause illness or death
protective: vaccine must protect against illness resulting from exposure to live pathogen
Gives sustained protection: protection must last for several years
Induces neutralizing antibody: some pathogens infect cells that cant be replaced, neutralizing AB is essential to prevent infection of these cells
induces protective t-cells:
Practical considerations: low cost
