Vaccines and Vaccine Development Flashcards
1
Q
Define Immunisation
- different forms
A
an artificial process by which an individual is rendered immuneTerm includes:
– Passive immunisation – no immune response in the recipient
– Active immunisation (vaccination) – recipient develops a protective adaptive immune response
2
Q
What is Passive Immunisation?
A
- 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
- protection is temporary
- can be used to make anti-toxins
3
Q
What is the disadvantage of using Horse serum to make diptheria anti-toxins?
A
- The proteins on horse antibodies induce anti-antibodies
- Following this between a week and 10 days after inoculation the antibodies will form complexes with the horse immunoglobulin and inactivate it
- The complexes can be deposited and cause secondary immune complex disease
- Horse antitoxin is more rabidly eliminated than human antitoxin - half-life of human IgG is ~20days vs 5days horse
- Repeat administration of horse anti-serum can cause severe anaphylactic shock
4
Q
What are clinical symptoms of Immune Complex disease?
A
chills, fever, rash, urticaria, arthritis, and glomerulonephritis.
these usually present them selves 7-10 days after coming into contact with the offensive antigen
5
Q
Give examples of Passive Immunisation in vaccines
- effect
A
- Immunoglobulin replacement in antibody deficiency
- taken from donors
- VZV prophylaxis eg during exposure during pregnancy
- Anti-toxin therapies eg snake anti-serum
- Diphteria anti-toxin using anti-toxins form horses infected with it
- protection is temporary
6
Q
How would the following presentation of Vassilis zoster zirus (VZV) in pregnancy be managed
- Definite history of previous chickenpox
- No history of chickenpox or unsure
- No history of chickenpox, or unsure
A
- Definite history of previous chickenpox
- not indicated in the blood after VZV serology
- reassure patients
- not indicated in the blood after VZV serology
- No history of chickenpox or unsure
- VZV IgG positive
- reassure patient
- VZV IgG positive
- No history of chickenpox, or unsure
- VZV IgG negative or equivocal
- administer VZV immunoglobulin to protect against primary infection
- VZV IgG negative or equivocal
7
Q
What is Active Immunization (vaccination)
A
- 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
8
Q
What are important requirements for vaccines?
A
- safe to use and not cause the disease they aim to prevent
- must have minimal side effects
- must be long lasting
- easy to store and transport
- as cheap as possible
9
Q
What are general principles of vaccines?
A
- adminstered to target cohorts in advance of exposure to pathogen
- enough people need to be vaccinated to reach heard immunity
- vaccines are given to healthy people so risk to benefit ratio requires vaccines to have high safety standards
- most vaccines work by generating a long-lasting, high-affinity IgG antibody response
- strong CD4 T cell response is important for this
- ‘problem’ diseases are generally those where the immune system cannot eliminate infection or generate long-lasting protective immunity during natural infection
- MTB, HIV,malaria
10
Q
What goes into vaccines?
(3)
A
- Antigen: To stimulate an antigen-specific T and B cell response
-
Adjuvants: Immune potentiators to increase the immunogenicity of the vaccine
- most act on toll-like receptors
- ‘Excipients’: Various diluents and additives required for vaccine integrity
11
Q
How are active vaccines classified in terms of the antigen?
A
12
Q
What are live attenuated vaccines?
- how are they formed?
A
- Live but attenuated organisms used
- attenuated –> reduced
- Achieved by prolonged culture ex vivo in non-physiological conditions
- This selects variants that are adapted to live in a culture
- These variants are viable in vivo but are no longer able to cause disease in humans
13
Q
Give examples of Live-attenuated vaccines
(4/7)
A
- Measles, Mumps, Rubella (MMR)
- Polio (Sabin)
- BCG
- Cholera
- Zoster
- VZV (not routinely used for primary prevention in UK at present)
- Live influenza (not main product in UK at present)
14
Q
What are the Pros of live attenuated vaccines?
A
- Replication within-host, therefore produces highly effective and durable responses
- In the case of viral vaccine, intracellular infection leads to a 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
15
Q
What are the Cons of live vaccines?
A
- Storage problems, short shelf-life
- needs a cold chain
- May revert to wild type
- Eg vaccine-associated poliomyelitis: around 1 in 750 000 recipients
- Immunocompromised recipients may develop clinical disease
16
Q
Give an overview of the Varicella-Zoster Virus
A
- Primary infection = chickenpox
- Cellular and humoral immunity provide lifelong protection, but viruses establish permanent infection of sensory ganglia –>
- Viral reactivation=zoster
- Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
17
Q
Give an overview of the Varicella-Zoster Vaccine
- how does it work
- efficacy in the UK
A
- Live-attenuated VZV, works by induction of anti-VZV antibodies
- 95% effective at preventing chickenpox
- Attenuated virus does establish the infection of sensory ganglia, but subsequent zoster is probably rare
- 3-5% mild post-vaccination varicella infection
- Not on UK schedule at present, because:
- VZV is a fairly benign childhood infection
- ?Schedule is already crowded and controversial
- Safety concerns based on evidence from other countries
- ‘Disease shift’ to unvaccinated adults, in whom VZV is less well tolerated
- Increase in zoster – probably reduced immune-boosting in adults
18
Q
Give an overview of Zoster infection and age
A
- The incidence of zoster increases with age, in parallel with declining cell-mediated immune responses to zoster
19
Q
Explain the Zoster vaccination
- type of vaccine
- effect and use
A
- Similar VZV preparation to that used for primary disease, 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
20
Q
What is Poliomyelitis
A
- 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
21
Q
What are the two Polio vaccines?
- what type of vaccines are they
- efficacy?
A
-
Sabin oral polio vaccine (OPV) = live-attenuated
- Viable virus can be recovered from stool after immunisation
- Highly effective, and also establishes some protection in the non-immunised population
- 1 in 750 000 vaccine-associated paralytic polio
- better suited to endemic areas where benefits of higher efficacy outweigh risk of vaccine-associated paralysis
-
Salk injected polio vaccine (IPV) = inactivated
- Effective, but herd immunity inferior
- better suited in lower prevalence areas (UK switched in 2004)
22
Q
Explain the Tuberculosis infection
A
- During primary infection, MTB establishes infection within phagolysosomes of macrophages.
- Macrophages present TB antigen to MTB-specific CD4 T cells, which secrete IFN-g
- this activates macrophages to encase TB in the granuloma.
- It may be visible as a calcified lesion on plain CXR (Ghon focus)
- Most TB thought to be re-activation of this primary infection
34
Q
Explain Vaccine Conjugation
A
- Naive B cell expressing surface IgM recognises polysaccharide antigen.
- Antigen is internalised together with the protein conjugate
- Conjugate is processed in the class II pathway.
- Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor.
- T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate
36
Q
Explain the development Human Papillomavirus Vaccination
- what does the vaccine protect against?
A
- HPV subtypes 16 and 18 infection major causal factor in cervical carcinoma
- vaccine protects against this
- Vaccine development problematic as HPV is difficult to culture so they used
- Subunit vaccines are ‘empty virus particles’ that prevent primary infection
- viral particles which only have the capsid protein
- Quadrivalent vaccine covers additional HPV strains (genital warts, penile cancer)
41
Q
How is Intracellular mRNa stability achieved?
A
- A specially modified Nucleotide positioned at the 5’ end (Cap)
- A poly (A) tail (length)
- The composition and structure of the 3’ untranslated regions (3’UTR)
49
Q
What is the effect of therapeutic antibodies on COVID-19?
A
- therapeutic B-cells antibodies recognising the spike protein are administered to individuals to prevent serious disease courses
- treatment with REGN-COV2 resulted in statistically significant reduction in the time-weighted average daily change from baseline in viral load
