Vaccines & Vaccine development Flashcards
What is immunisation?
artificial process by which an individual is rendered immune
- passive or active
Describe passive immunity
- no immune response in recipient
- preparations of antibodys from hyperimmune donors (animal/human)
- e.g anti-snake venom, VZV prophylaxis in pregnancy
- immunity acquired is TEMPORARY
Describe active immunity
Why is this important in public health and prevention of disease?
- aka VACCINATIONS
- recipient develops a protective adaptive immune response without causing clinically apparent infection
Cheap and effective way of decreasing morbidity and increasing survival
State 5 conditions required for a vaccination to be most effective
- administered to targeted cohorts in ADVANCE
- herd immunity (>90%)
- meet high safety standards
- generate long lasting high affinity IgG antibody response (enough to prevent primary infection)
- requires strongCD4 T cell response
- natural exposure results in protective immunity
Briefly describe the use of passive immunity in VZV prophylaxis in pregnancy
- “Chickenpox” infection in pregnancy causes fetal complications
- VZIG (prophylaxis) is indicated if VZV IgG is negative in maternal blood, otherwise reassure
State 3 diseases for which vaccinations have poor efficacy
Suggest why
Common cold, HIV, malaria
Immune system cannot eliminate infection or generate long lasting protective immunity
What is inside a vaccine?
Antigen
Adjuvant
Excipients
* Active vaccines can be made from whole organisms (live attenuated or inactivated) or subunits
How are live attenuated vaccines prepared
Give 5 examples of vaccinations prepared in this way
Prolonged culture ex vivo in non-physiological conditions which selects variants adapted to live in culture
- These are able to live in vivo but no longer cause disease
MMR, Polio, BCG, Cholera, Zoster, VZV, Live influenza
State 4 advantages of using live attenuated vaccines
- replication in host produces highly effective and durable responses
- in viral cases, intracellular infection leads to good CD8 response
- repeated boosting not required
- may get secondary protection of unvaccinated people who are infected (e.g. polio)
State 3 disadvantages of using live attenuated vaccines
- storage problems due to short half life
- may revert to wild type e.g. in vaccine associated poliomyelitis
- immunocompromised recipient may develop disease
Describe the consequences of primary infection with VZV
What happens in reactivation?
How does a vaccine work in this case?
Primary infection (chickenpox) provides lifelong immunity but virus establishes permanent infection of sensory ganglia
Reactivation = zoster. Particularly in elderly patients. It is debilitating and causes long term neuropathic pain
Vaccine induces anti-VZV anitbodies (95% effective against chickenpox) but not used in UK.
- 3-5% develop post vaccination mild varicella infection
How has the disease shift of VZV impacted the tolerance of the virus in the older population?
- VZV benign childhood infection is less tolerated if contracted by an unvaccinated adult
- Increased development of zoster (less immune boosting in adults)
- The incidence of zoster increases with age
- Vaccination is similar to VZV but higher dose and its aim is to boost memory T cell response to VZV. The result is that there is a 50% decreases in incidence and less severe and complicated cases
Describe how the infection resulting in poliomyelitis occurs
- enterovirus establishes infection in oropharynx and GIT (alimentary phase)
- spreads to peyers patches and disseminates into lymphatics
- haematogenous spead (viremia phase)
- 1% develop neurological phase: denervation and flaccid paralysis due to replication in motor neurons in spinal cord, brainstem and motor cortex
There are two types of vaccines against poliomyelitis.
Describe the production, efficacy and side effects of the SABIN ORAL POLIO VACCINE (OPV)
LIVE ATTENUATED VACCINE
- viable virus obtained from stool post-immunisation
- highly effective and also establishes protection in non-immunised population
- better suited to endemic areas where benefits of high efficacy outweigh risks
- side effects: 1/750000 develop vaccine associated paralytic polio
There are two types of vaccines against poliomyelitis.
Describe the efficacy of the SALK INJECTED POLIO VACCIN (IPV)
INACTIVATED VACCINE
- effective although herd immunity inferior to OPV
- switched in 2004
What happens in primary infection of mycobacterium tuberculosis?
How does it appear on XR?
- MTB establishes infection in phago-lysosomes of macrophages. Macrophages present TB antigen to specific CD4 T cell which secretes IFN-g which activates macrophages to encase TB in granuloma
- Granuloma appears as calcified lesion
Describe the use, aims, administeration and efficacy of the tuberculosis vaccine
- Licensed vaccine is BCG produced by repeat passage of a non-MTB e.g. mycobacterium bovis
- Aims: increase Th1 (IFN-g) cell responses to M.bovis –> confer immunity to MTB
- Administered via intradermal injection
- 80% effective in preventing disseminated TB/ TB meningitis in kids. Little/no effect on pulmonary TB
How are killed (inactivated) vaccines prepared?
How do they work?
Give 2 examples of vaccinations prepared in this way
- Entire organism used but physical/chemical methods used to destroy viability (e.g. formaldehyde)
- Stimulate B cells, taken up by APCs to stimulate CD4 T cells. They elicit minimal CD8 response as vaccine cannot undergo intracellular replication.
e.g. Hep A, Influenza
State 3 advantages and disadvantages of using killed (inactivated) vaccines
ADVATANGES
- No potential for reversal
- Safe for immunocompromised
- Stable in storage
DISADVANTAGES
- mainly CD4/AB response
- response less durable that live (booster required)
- higher uptake needed for herd immunity
How does the influenza virus work?
Protective AB responses largely directed against haemagglutinin and neuramidase and work by blocking entry to cells, blocking release of new virons from infected cells and promoting ADCC (antibody-dependent cellular cytotoxicity)
Why is an influenza vaccine not all that effective?
- Target antigens prone to mutations (autogenic drift) which is responsible for seasonal variation
- Major changes occur when viral strains recombine (e.g. with animal strain) –> pandemic influenza
How are subunit vaccines prepared?
How do they work?
Give 2 examples of vaccinations prepared in this way
- only use critical part of organism which is then purifies from organism or generated by recombinant techniques
- protection depends on eliciting CD4 and AB responses
e.g. toxoids, tetanus vaccine
What are toxoids?
How do they produce immunity?
- Chemically detoxified toxins
- e.g. toxin producing bacteria: C,diphtheriae, C.tetani, B.pertussis
- retain immunogenicity
- work by stimulating AB response; antibodies neutralise toxin
How does the tetanus vaccine work?
- preformed high affinity IgG neutralise toxin in circulation; immune complexes then remove via spleen
- anti-toxin can also be given in extablished cases (passive immunity
What are polysaccharide capsules?
Where are they found? How can they be used therapeutically?
Disadvantages of their use?
- Thich PS coat bacteria such as S. pneumonaie, N.meningitidis which makes them resistant to phagocytosis
- Vaccines against these bacteria are formed from PS coat and their aim is to induce IgG antibody that improves opsonisation
- Suboptimal as PS weakly immunogenic. If no peptide –> no T cell response and only stimulates small population of T-independent B cells
How is the efficacy of vaccines made from polysaccharide coats boosted?
Explain the process.
Vaccine conjugation boosts immune response by attaching protein carrier to PS antigen
- naive b cell expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with protein conjugate
- conjugate is processed in the class 2 pathway. Naive B cell peptides from conjugate to a Th cell with correct receptor
- T cell helps the b cell to perform affinity maturation but antibody is specific for polysaccharide and not the protein conjugate.
What must be considered when using/making recombinant protein subunit vaccines?
Eg of vaccines made in this way
- need to know key immunogenic proteins required
- proteins expressed in lower organisms
- purified to produce vaccine
- e.g. Hep B (uses surface antigen), HPV
- increasingly in use
Why is HPV vaccination important?
Why was its development difficult?
- subtypes 16 and 18 cause cervical carcinoma
- vaccine development difficult due to HPV difficulty culturing
- subunits vaccines are ‘empty virus particles’ that prevent primary infection (Quadravalent vaccine covers additional HPV strains)
Give three advantages and disadvantages of recombinant protein subunit vaccines
ADVANTAGES
- extremely safe
- work well where primary infection may be prevented by AB response
- works when virus cannot easily be cultured e.g. HPV, Hep B
DISADVANTAGES
- development requires detailed knowledge of virology, pathogenesis and immunology
- specialised and expensive production
- weaker immune responses- boosting often needed and varied response rates
What are adjuvants?
Examples?
How do they work?
Immune potentiators to increase the immunogenicity of the vaccine
- boost immune response to antigen
- widely used despite lack of understanding of MOA
- examples: alum, lipopolysaccharides
- bind to PRRs on APCs which enhance co-stimulation and cytokine secretion, which ensures robust T/B cell response
- novel aduvants: TLR ligands e..g CPG repeats
How do novel DNA vaccines work?
plasmid DNA encodes vaccine antigen applied, taken up by cells, transcribed and translated –> elicits host immune response
- mainly performed in mice, poorly immunogenic in humans
Novel vaccines are using viral vectors. How does this work?
Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens
Used in live attenuated vaccine
Use restricted to animals to date
