L19 vaccines Flashcards
Immunisation?
Immunisation: “process whereby a person is made immune or resistant to an infectious
disease, typically by the administration of a vaccine”
(World Health Organization, WHO)
(Process of conferring increased resistance or decreased susceptibility to infection)
A procedure designed to increase concentrations of antibodies (b cells)
and/or effector T cells which are protective against infectious agents
(and cancer)
Can be performed before exposure to infection organisms
= immunoprophylaxis or prophylactic vaccination
(designed to prevent disease from developing in healthy individuals) given before exposure e.g: infant vaccinations
Or during an active infection (or cancer) = therapeutic vaccination
(designed to treat an existing infection or cancer by strengthening
the body’s natural anti-microbial/viral or anti-tumour immune response)
Fundamental principle of vaccination:
To administer a killed or attenuated (reduced in potency) form of an
infectious pathogen (bacteria, virus) or a component of a microbe which
does not cause disease but elicits an immune response that provides
protection against infection or exposure to the live, pathogenic microbe
(establishing immunity without causing disease or adverse toxicity -
successful vaccination).
Requirements for an effective vaccine?
safe and cost-effective
The success of vaccination
Vaccines are most effective if the infectious agent does not:
* establish latency
* does not undergo antigenic variation
* and does not interfere with the host immune response
* It is difficult to effectively vaccinate against microbes such as
HIV, which establishes latent infection and is highly variable.
* Vaccines are also most effective against infections that are
limited to human hosts and do not have animal reservoirs
Most vaccines in use today work by inducing humoral immunity
Antibodies prevent infections by neutralising and clearing microbes before they
establish themselves in the host - prevent reinfection.
The best vaccines are those that stimulate the development of long-lived
plasma cells that produce high-affinity antibodies as well as memory B cells -
humoral immune responses induced by the germinal centre GC reaction which
requires help provided by antigen-specific CD4+ T follicular helper cells
How do vaccines work?
- Vaccine is phagocytosed by
an APCs (DCs) - DCs – play a key role in
activating T cells which
become helper T cells - Activated helper T cells go
on to activate B cells - These activated B cells then
divide into 2 types of immune
cell types – - antibody-producing plasma
cells - and most importantly
memory B cells - Linked to secondary immune
response (the body mounts a
quicker, more robust attack
on the pathogen)
Two mechanisms by which immunisation can be achieved?
- Active immunisation - can be achieved through natural infection by a
pathogen or it can be acquired artificially through vaccines
e.g. antibodies produced in response to an infection (natural measles
virus) or antibodies produced in response to a vaccine (live, attenuated or
toxoid)
* Individuals make their own antibodies – induction of an adaptive immune
response* - Passive immunisation - individuals gain protective antibodies
from another individual who has produced them e.g: from mother through breast feeding.
Passive immunisation?
Occurs naturally by transfer of maternal antibodies (Abs) (IgG) across the placenta
or in breast milk
Abs (IgG and IgA) present in breast milk or across the placenta.
Protection against: diptheria, mumps, measles etc for first 6 months of life
Protective immunity can be conferred by the administration of specific
antibodies collected from actively immune individuals (humans or animals)
VariZIG (Varicella Zoster Immune Globulin (Human)) is a sterile
lyophilised preparation of purified human immunoglobulin G (IgG)
containing antibodies to varicella zoster virus, VZV (chickenpox). It
provides passive immunisation for non-immune individuals exposed to VZV,
reducing the severity of varicella infections
- Injection with preformed specific antibodies
Protection against: Hepatitis A, rabies, tetanus - Injection with antitoxin (antibodies) can be live-saving
Protection against: botulism, snake / spider bite (poisonous)
Passive immunisation protection for patient is short-lived because the immunisation
does not induce active immunological memory and only lasts
as long as the injected antibody persists in the body
Active immunisation?
Naturally following exposure to an infection
Medically via vaccination - “artificial infection”
- Live attenuated or killed organisms
(bacteria or viruses)
- subunit (antigen) vaccines
- conjugate vaccines
- synthetic vaccines
- viral vectors
- DNA and RNA vaccines
Elicit/induce active protective immunity
and immunological memory
*vaccine approaches
Live, attenuated or inactivated/killed
bacterial and viral vaccines?
Effective vaccines are composed of intact microbes that are treated in such
a way that they are attenuated OR killed, so they no longer cause disease,
while retaining their immunogenicity
Advantage of attenuated microbial vaccines is that they elicit all the innate and
adaptive immune responses (both humoral and T cell mediated)
However, the inactivated (killed) bacterial vaccines generally induce limited
protection and are effective for only short periods
Live, attenuated viral vaccines are usually more effective e.g. polio, measles,
and yellow fever.
Early approach for producing attenuated viruses was repeated passage in cell
culture
More recently, temperature-sensitive and gene deletion mutants have been
generated
Viral vaccines often induce long-lasting specific immunity, so immunisation of
children is sufficient for lifelong protection
So good cus they activate innate and adaptive-memory b and t cells produced. The innactibated killed are not as potent, limited protection, do not have long lasting effects.
Learn examples of pathogens associated with vacines
Attenuated: formed in lab through repeat passage in cell culture.
In live-attenuated
vaccines, like the
measles, mumps, and
rubella shot, weakened
viruses incorporate their
genetic instructions into
host cells, causing the
body to churn out viral
copies that elicit
antibody and CD4 and
CD8 T cell response
problems with attentuated viral or bacterial vaccines?
The major concern with attenuated viral or bacterial vaccines is safety
The live-attenuated oral polio vaccine has nearly eradicated the disease, but in
rare cases the virus in the vaccine is reactivated and itself causes serious polio
Success of worldwide vaccination is creating the unusual problem that the
vaccine-induced disease, although rare, could become more frequent than the
naturally acquired disease! So vacine can be infectous.
Solution? reverting to the killed virus vaccine to complete the eradication
program (or 3rd generation vaccines)
A widely used inactivated vaccine of considerable public health importance is
the influenza or flu vaccine. Influenza viruses are grown in chicken eggs
Innactivated vaccine: Flu shot: Trivalent inactivated (killed) vaccine given intramuscularly
3 of the most frequently encountered influenza strains are selected every year
and incorporated into this vaccine
Purified antigen (subunit) vaccines?
Purified antigen (subunit) vaccines: eliminate safety concerns with live vaccines, antigen purified from pathogen. Normally given together with an adjuvent e.g: tetanus
2nd -generation vaccines produced to eliminate the
safety concerns associated with attenuated microbe
vaccines
Subunit vaccines are composed of antigens purified
from microbes or inactivated toxins and are usually
administered with an adjuvant*
Purified antigen vaccines are used for the prevention of
diseases caused by bacterial toxins
Toxins can be rendered harmless without loss of
immunogenicity, and such toxoids induce strong
antibody responses
Diphtheria and tetanus are two infections whose life-
threatening consequences have been largely
controlled because of immunization of children with
toxoid preparations
adjuvent?
*adjuvant is a chemical
substance that can be
added to a vaccine in
order to enhance the
immune response (via
DC cell activation)
Adjuvants
The initiation of T cell–dependent immune
responses against protein antigens requires
that the antigens be administered with
adjuvants
Adjuvants elicit innate immune responses, with
increased expression of co-stimulators and
production of cytokines, such as IL-12, that
stimulate T cell growth and differentiation
Only two are approved for patients—
aluminium hydroxide gel (which appears to
promote mostly B cell responses)
and a lipid formulation called Squalene that
may activate phagocytes
Adjuvants: promote innate immune response (dendritic cells)
The initiation of T cell–dependent immune
responses against protein antigens requires
that the antigens be administered with
adjuvants
Adjuvants elicit innate immune responses, with
increased expression of co-stimulators and
production of cytokines, such as IL-12, that
stimulate T cell growth and differentiation
Only two are approved for patients—
aluminium hydroxide gel (which appears to
promote mostly B cell responses)
and a lipid formulation called Squalene that
may activate phagocytes
Purified antigen (subunit) vaccines (more)
Bacterial polysaccharide antigen vaccines
are used against pneumococcus
and Haemophilus influenzae
However, polysaccharides are T-independent
antigens, they tend to elicit low-affinity
antibody responses and are poorly
immunogenic in infants (who do not mount strong T
cell-independent antibody responses)
High-affinity antibody responses may be
generated against polysaccharide antigens
even in infants by coupling the
polysaccharides to proteins to
form conjugate vaccines: weak prufiied antigen given in combination with strong antigen to help immune response like a carrier protein. Used when bacterial polysaccharide antigen. Help t cell response, enable th to enable antibody production. These types do not gen cd8 responses but cd4. So not good for viruses as they often presented through mhc class 1 pathway so mhc class 1 aka cd8 needed.
These conjugate vaccines elicit helper T cells.
to simulate germinal centre GC reactions,
which would not occur with simple
polysaccharide vaccine
