T1 l7:vaccines Flashcards
what is immunisation
Immunisation is an artificial process by which an individual is rendered immune
what are the different categories of the immune system
- Passive immunisation – no immune response in recipient
- Active immunisation (vaccination) – recipient develops a protective adaptive immune response
expand on passive immunisation
Immunity conferred without an active host response on behalf of recipient
Passive vaccines are preparations of antibodies taken from hyper-immune donors, either human or animal
Examples:
Immunoglobulin replacement in antibody deficiency
VZV prophylaxis eg during exposure during pregnancy
Anti-toxin therapies eg snake anti-serum
expand on active immunisation
Immunity conferred in recipient following the generation of an adaptive immune response
General principle is to stimulate an adaptive immune response without causing clinically-apparent infection
what are the 2 general principles of active immunity
1- Vaccination of sufficient numbers impacts the transmission dynamic so that even unimmunised individuals are at low risk – called herd immunity
As vaccines are given to healthy individuals, the risk-to-benefit ratio requires that vaccines meet high safety standards
2- Most vaccines work by generating a long-lasting, high-affinity IgG antibody response
These antibodies are sufficient to prevent primary infection
A strong CD4 T cell response is a pre-requisite for this
The most effective vaccines are for diseases where natural exposure results in protective immunity
what forms a vaccine
Antigen-
To stimulate an antigen-specific T and B cell response
Adjuvants-
Immune potentiators to increase the immunogenicity of the vaccine
‘Excipients’-
Various diluents and additives required for vaccine integrity
how do you classify active vaccines based on the antigen
can be subunit- toxoids, capsular polysaccharide, recombinant subunit , conjugated polysaccharide
it can also be a derivation of the whole organism:
- Live-attenuated
- inactivated (killed)
how do you classify active vaccines based on the antigen
can be subunit- toxoids, capsular polysaccharide, recombinant subunit , conjugated polysaccharide
it can also be a derivation of the whole organism:
- Live-attenuated
- inactivated (killed)
what are the examples of live-attenuated vaccines
Measles Mumps Rubella Polio (Sabin) BCG Cholera Zoster VZV (not routinely used for primary prevention in UK at present) Live influenza (not routinely used in UK at present)
evaluate the use of live vaccines
Advantages:
Replication within host, therefore produces highly effective and durable responses
In case of viral vaccine, intracellular infection leads to good CD8 response
Repeated boosting not required
In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
Disadvantages:
Storage problems, short shelf-life
May revert to wild type
Eg vaccine associated poliomyelitis: around 1 in 750 000
recipients
Immunocompromised recipients may develop clinical disease
describe the varicella-zoster vaccine
Primary infection = chickenpox
Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
Viral reactivation=zoster
Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
how does the VZV vaccine work
Live-attenuated VZV, works by induction of anti-VZV antibodies
95% effective at preventing chickenpox
Attenuated virus does establish infection of sensory ganglia, but subsequent zoster is probably rare
what is the zoster vaccination
Similar VZV preparation, but much higher dose
Aims to boost memory T cell responses to VZV
In over 60s, 50% reduction in zoster incidence after vaccination compared to controls; reduced severity and complications amongst vaccinated cases
describe poliomyeitis
Enterovirus establishes infection in oropharynx and GI tract (alimentary phase)
Spreads to peyers patches then disseminated via lymphatics
Haematogenous spread (viremia phase)
1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis
Salk vs Sabin Polio vaccine
Sabin oral polio vaccine (OPV) = live-attenuated
- Viable virus can be recovered from stool after immunisation
- Highly effective, and also establishes some protection in non-immunised population
- 1 in 750 000 vaccine-associated paralytic polio
Salk injected polio vaccine (IPV) = inactivated
-Effective, but herd immunity inferior
OPV better suited to endemic areas, where benefits of higher efficacy outweigh risks of vaccine-associated paralysis. UK switched to IPV in 2004
describe infection of Tb
During primary infection, MTB establishes infection within phago-lysosomes of macrophages. Macrophages present TB antigen to MTB-specific CD4 T cells, which secrete IFN-g – this activates macrophages to encase TB in granuloma.
May be visible as a calcified lesion on plain CXR (Ghon focus)
Most TB thought to be re-activation of this primary infection
describe the vaccination for Tb
Only licensed product is BCG (bacille Calmette-Guerin)
Produced by repeat passage of a non-tuberculus mycobacterium: Mycobacterium bovis
Aims to increase Th1 (IFN-g) cell responses to M bovis, thereby conferring protection against MTB
Given by intradermal injection
80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
is the TB vaccine alive?
Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde)
Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells
Probably elicit minimal CD8 response, as the vaccine cannot undergo intracellular replication
Responses less robust compared to live-attenuated vaccines
Examples
- Hepatitis A
- Influenza (standard vaccine – live-attenuated also available but not routinely used)
evaluate ‘killed’ vaccines
advantage:
No potential for reversion
Safe for immunocompromised
Stable in storage
disadvantage:
Mainly CD4/ antibody response
Responses less durable then live vaccines
Generally boosters required
Higher uptake generally required to achieve herd immunity
Difficulties of influenza vaccination
Target antigens prone to mutation (antigenic drift) causing seasonal variation – therefore vaccine produced annually based on predictions
CDC provide candidate virus strains to manufacturer; injected into fertilised hens eggs and virus then harvested (inactivated for standard vaccine)
More major changes (antigenic shift) occur when viral strains recombine – eg with animal strain, causing pandemic influenza
describe subunit vaccines
Uses only a critical part of the organism
Components may be:
- purified from the organism or
- generated by recombinant techniques
-Protection depends on eliciting CD4 and antibody responses
Subunit vaccines: toxoids
Many examples relate to toxin-producing bacteria:
- Corynebacterium diphtheriae
- Clostridium tetani
- Bordatella pertussis
Toxins are chemically detoxified to ‘toxoids’
Retain immunogenicity
Work by stimulating antibody response; antibodies then neutralise the toxin
describe tetanus
Pre-formed high-affinity IgG antibodies can neutralise the
toxin molecules in the circulation; the immune complexes
are then removed via the spleen
Anti-toxin can also be given in established cases (passive immunisation)
describe subunit vaccines: polysaccharide capsules
Thick polysaccharide coats of Streptococcus pneumoniae and Neisseria meningitidis make them resistant to phagocytosis
Vaccines for these organisms formed of purified polysaccharide coats
Vaccines formed of purified polysaccharide coats; aim to induce IgG
antibodies that improve opsonisation
Suboptimal as polysaccharides are weakly immunogenic:
- No protein/ peptide, so no T cell response
- Stimulate a small population of T-independent B cells
Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen
