Vaccines and Vaccine Development Flashcards
Define Immunisation
- different forms
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
What is 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
- protection is temporary
Give examples of Passive Immunisation in vaccines
- effect
- Immunoglobulin replacement in antibody deficiency
- taken from donors
- VZV prophylaxis eg during exposure during pregnancy
- Anti-toxin therapies eg snake anti-serum
- protection is temporary
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
- 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
What is Activ Immunisation (vaccination)
- 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 general principles of vaccines?
- 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
What goes into vaccines?
(3)
- 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
How are active vaccines classified in terms of the antigen?
What are live attenuated vaccines?
- how are they formed?
- 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
Give examples of Live-attenuated vaccines
(4/7)
- 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)
What are the Pros of live attenuated vaccines?
- 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
What are the Cons of live vaccines?
- 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
Give an overview of the Varicella-Zoster Virus
- 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
Give an overview of the Varicella-Zoster Vaccine
- how does it work
- efficacy in the UK
- 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
Give an overview of Zoster infection and age
- The incidence of zoster increases with age, in parallel with declining cell-mediated immune responses to zoster
Explain the Zoster vaccination
- type of vaccine
- effect and use
- 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