Varicella Zoster virus - Primarily causes chickenpox - Can permanently infect the sensory ganglia even though cellular and humeral immunity provides life-long protection (becomes zoster when reactivated)

Similar to VZV vaccine but with a higher dose - Boosts memory T cell response to VZV Results (in >60) - Reduces zoster incidence - Reduces severity and complications

Vaccines Flashcards by aderonke adesanoye

Immunisation

Artificial process by which an individual is rendered immune

Passive
Active

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Passive immunisation

Type of immunisation that produces no active immune response in the host.
- They are antibodies extracted from a hyper-immune donor (human or animal)

Protection is temporary
- Due to no memory cells

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Passive immunisation examples

Antibody deficiency
- Immunoglobulin replacement

VZV (Varicella zoster virus) prophylaxis
- Esp. exposure during pregnancy

Anti-toxin therapies
- Snake anti-serum

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VZV prophylaxis during pregnancy

VZV can cause fatal complications so exposure is treated immediately with vaccine.

When to vaccine
- No history/ unsure history about chickenpox AND VZV IgG negative/ equivocal

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Active immunisation

Immune acquired by a host through the generation of an adaptive immune response.

The vaccine stimulates an immune response without causing the fully clinical infection.

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Herd immunity

Vaccinating a sufficient amount of people in a population (i.e around 90%), so that unimmunised individuals are at low risk.

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Principals of vaccinations

Must be given to cohort before exposure to pathogen.

Herd immunity can minimise those that contract disease.

Most generate a long-lasting high IgG antibody response

Most effective vaccine are for disease where natural exposure results in protective immunity.

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Problem diseases to vaccinate

Problem disease are usually where the immune system cannot eliminate the infection or create a long-lasting protective immunity.

Examples

Common cold
Mycobacterium TB
HIV
Malaria

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Components of a vaccine

Antigen

Whole organism (live-attenuated or inactive)
Subunit

Adjuvants
- increases immunogenicity of vaccine

Excipients
- increases vaccine integrity

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Live-attenuated vaccines examples

Measles

Mumps

Rubella

Polio

BCG

Cholera

Zoster

VZV

Live influenza

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Live-attenuated vaccines

Vaccinate containing pathogen that are viable in vivo but unable to cause disease.
- Pathogens that have adapted to live ex vivo in the non-physiological conditions in culture are selected

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Pros of live vaccines

Pros
- The pathogens are alive, so are able to replicate in hose, hence more immunogenic.

Can stimulate good CD8 responses with viral vaccines as viruses can cause intracellular infections.
Does not required repeated boosting
Can get secondary protection of unvaccinated individuals, infected with live-attenuated vaccine strain in some disease

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Cons of live vaccines

Short shelf live due to very specific culturing conditions.

Pathogens can revert to wild type
- Cause full blown disease

Can cause full blown disease in immunocompromised individuals.

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VZV

Varicella Zoster virus

Primarily causes chickenpox
Can permanently infect the sensory ganglia even though cellular and humeral immunity provides life-long protection (becomes zoster when reactivated)

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VZV vaccine

Live-attenuated
- Induces anti-VZV antibodies

95% effective in preventing varicella

3-5% post-vaccination varicella infection

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Reasons why VZV vaccine is not scheduled in the UK

Fairly benign childhood infection

Safety concerns that it would cause a disease shift to unvaccinated adults where VZV is less tolerated.

Could increase zoster and reduce immune boosting in adults

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Zoster vaccination

Similar to VZV vaccine but with a higher dose
- Boosts memory T cell response to VZV

Results (in >60)

Reduces zoster incidence
Reduces severity and complications

Poliomyelitis (polio)

Enterovirus- GIT, oropharynx
- Spreads to Peter’s patch–> lymphatics–> haematogenous spread

Neurological phase (1%)
- Motor neurones
- Brain stem
- Motor cortex
= flaccid paralysis due to denervation

Salk injected polio vaccine (IPV)

Inactivated vaccine

Effective but is herd immunity inferior to Sabin

Does not cause vaccine-associated polio paralysis

Sabin oral polio vaccine

Live-attenuated vaccine

Can be recovered from stool after immunisation
Very effective, and establishes secondary protection
Better suited from endemic areas affected

BUT
- Vaccine-associated paralytic polio (1:750,000)

TB infection

Bacteria infects macrophages and is presented to CD4 T cells

release of IFN-g
activates granulomas

TB Vaccination

BCG (Bacille Calmette Guerin)
- Non-TB bacterium Myocobacterium bovis (bovine)

Aims
- Increases Th-1 cell response to M bovis (increase in IFN-g)= protection against MTB

Administration
- Intradermal injection

Effectiveness

80% effective in preventing disseminated TB/ TB meningitis in children.
Little/ no effect on pulmonary TB

Inactivated vaccines

Vaccine with unviable pathogen
- Usually killed by certain methods, i.e formaldehyde.

Function

Stimulates B cells and APCs
Stimulates antigen specific CD4+ T cells

Less robust response that live-attenuated vaccines

Examples of inactivated vaccines

Hep A

Influenza

Pros of killed vaccines

No potential reversion Safe for those immunocompromised Stable in storage

Cons of killed vaccines

Mainly CD4/ Ab responses - Less stimulation of CD8 T cells, like live vaccines Less durable response than live vaccines Higher uptake to achieve herd immunity

Influenza virus structure

External antigens: they are subtype and strain specific antigens of Influenza A virus - Hemagglutinin - Neuraminidase Internal antigens: type-specific proteins, determines whether A, B or C virus. - Matrix - RNP

Influenza vaccination

Mainly triggers antibody response that are directed against hemagglutinin and neuramidase (external antigens)

Difficulties with Influenza vaccine

Targets antigen prone to mutation - Seasonal variation, so new vaccine is produced annually. Major changes occur when viral strains combine- e.g with animal strain= pandemic influenza

Subunit vaccines

Live vaccine - Uses only a critical part of the organism Components obtained by: - Purifying from the organism - Generating via recombinant techniques Mechanism - Elicits CD4/ Ab response

Toxoids

Subunit vaccine Toxins are obtained usually from toxin-producing bacteria then detoxified. This stimulates Ab response--> toxin is then neutralised by Ab.

Tetanus vaccine

Toxoid vaccine Stimulates high-affinity IgG Ab to neutralise tetanus toxin - Immune complex then removed via spleen

Polysaccharide capsules

Subunit vaccine The polysaccharide coat of certain bacteria is administered to induce IgG antibodies - Improves opsonisation - Bacteria: S. pneumonia N. meningitides Problem - No protein, no T cell response - Only stimulates T-independent B cells Response can be boosted with vaccine conjugation - Protein carrier is attached to polysaccharide antigen.

Vaccine conjugation

Method of boosting immune response to polysaccharide antigens. 1. Polys. antigen is conjugated with protein - This is taken in via B cells using IgM receptor. 2. Class II MHC processes and presents peptides from conjugate to helper T cells 3. Helper T cells stimulate affinity maturation - Ab produced is specific for polysaccharide and not protein conjugate.

Recombinant protein subunit vaccine | - Include examples

Key immunogenic proteins are studied then stimulated to be produced in Lower organisms The proteins are then purified to produce a vaccine Examples - Hep B surface antigen - HPV vaccine

HPV vaccine

Recombinant protein subunit vaccine - Done as HPV is difficult to culture The vaccine includes empty sub-unit HPV particles- prevents primary infection Mainly covers strains that cause cervical carcinoma - HPV 16, 18 Quadravalent vaccine covers other strains

Pros of subunit vaccines

Very safe Works well where the primary infection can be prevented by Ab - + when the virus cannot easily be cultured (HPV, Hep B)

Cons of subunit vaccines

Requires very detailed knowledge of virology for its development Very specialised Expensive production Weaker immune response - Often require boosting

Adjuvants

Addition to vaccines to most immune response to antigen. Includes: Alum, LPS mechanism - Binds to PRR on APCs - Enhances co-stimulation and cytokine secretion= more robust T/ B cell response Includes: novel adjuvants (TLR ligands)

DNA vaccines

Novel vaccine Mechanism - Plasmid DNA that codes vaccine antigen is administered and taken up by cells - The antigen is transcribed and translated--> host. response Poorly immunogenic in humans atm

Viral vector

Novel approach to vaccines Benign virus is engineered to contain genes encoding immunogenic antigens - and cultured The engineered virus is then used as live-attenuated vaccine - Only used to animals atm