Lecture 9 - Vaccinations Flashcards by Sam Akhtar

Describe what is passive immunity?

-Without an active host response on behalf of recipient

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How are passive vaccines prepared and examples?

Antibodies taken from hyper-immune donors- either human or animal
Examples: immunoglobulin replacement in antibody deficiency
VZV prophylaxis -during exposure during pregnancy
Anti-toxin therapies
Protection is temporary

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what is recommended if a pregnant woman has no history of chickenpox and bloods are VZV IgG negative?

VZV immunoglobulin

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What is active immunisation?

Immunity conferred in recipient following the generation of an adaptive immune response
-general principle stimulate adaptive response without causing clinically apparent infection

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What is herd immunity?

-Vaccine need to be administered to targeted cohort in advance of exposure to the pathogen of interest in sufficient numbers- so un-immunised individuals are at low risk

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How do most vaccines work?

generate long-lasting, high affinity IgG antibody response

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What is the purpose of vaccines and what is role of CD4?

Antibodies produced as a result of vaccine are sufficient to prevent an infection
A strong CD4 T cell response is pre-requisite for this

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what goes into a vaccine?

Antigen: to stimulate 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

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what are the classifications of active vaccine on the basis of antigens?

whole organism —>live attenutaed or inactivated
-Subunit- Toxoids, capsular -polysaccharide
conjugated -polysaccharide
recombinant subunit

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Which vaccines are live but attenuated?

Prolonged culture ex vivo in non-physiological conditions
MMR
Polio
BCG
Chloera
Zoster

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what are the pros of the live vaccines?

Replication within the host- produces highly effective and durable responses
In viral response: intracellular infection leads to good CD8 response
repeated boosting not required
secondary protection

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What are cons of the live vaccines?

storage problems
short shelf life
may revert to wild type
immunocompromised recipients may develop clinical disease

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what is the primary infection caused by VZV and type of immunity?

Chicken pox
Cellular and humoural immunity provided
Life long protection but virus establishes permenant infection of sensory ganglia

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What happens when the viral infection is reactivated?

Zoster infection

- Particularly elderly and fairly debilitating and may cause neuropathic pain

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how VZV vaccine work?

by induction of anti-VZV antibodies

- attenuated virus does not establish infection of sensory ganglia but subsequent zoster is probably rare

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What is polio caused by?

Enterovirus establishes infection oropharynx and GI tract

- spreads to the peyers patch then disseminated via lymphatics

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what are the possible complications of polio?

-Neurological disease: replication in motor neurons in spinal cord brainstem and motor cortex leading to deneration and flaccid paralysis

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Compare Sabin oral polio vaccine vs Salk injected vaccine?

Sabin- Live attenuated : viable virus can be recovered from stool after immunisation
-Highly effective
-small risk of virus associated paralytic polio
SALK injected polio = Inactivated
-effective but herd immunity inferior
OPV better suited to endemic areas

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What happens during TB infection?

During primary infection- MTB establishes infection with 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
-Most TB thought to re-activation of this primary infection

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What is the vaccination for TB and how is produced?

BCG

produced by repeat passage of non-tuberculus mycobacterium- Mycobacterium bovis
aims to increase Th1 (IFN-g) in responses to M bovis thereby conferring protection against MTB
given as intradermal injection
effective against preventing disseminated TB/TB meningitis in children
No effect on pulmonary TB

what does inactivated (killed) mean in vaccines?

-Entire organism used- physical and chemical methods used to destroy the viability- formaldehyde

How does the inactivated trigger an immune response?

stimulates B cells
taken up APC cells to stimulate CD4 T cells
response less robust compared to live-attenuated vaccines

Give examples of inactivated vaccines?

Hep A

- Influenza standard

What are the advantages of using inactivated vaccines?

-No potential for reversion
-Safe for immuno-compromised
stable storage

What are the possible disadvantages of using inactivated vaccination?

- Weaker response compared to live vaccination - No CD8 response therefore response less durable - Boosters required - Higher uptake required to achieve herd immunity

What is influenza?

- Seasonal viral illness | - protective antibody response against: Heamagglutinin and neuramidase antigen

Why do we have to get influenza vaccination every year?

Natural antigenic ‘drift’ each year means that protective immune response from previous years may not be protective

What is antigenic shift?

when virus recombines with animal influenza strain

How are the influenza vaccination made?

- Virus grown in hen eggs | - killed vaccine is standard in UK

what are the features of the sub-unit vaccines?

-Uses only critical part of the organism -Components may be -Purified Generated by recombinat techniques -protection depends on eliciting CD4 antibody response

Name some of the vaccines that are produced using subunits?

-Many examples related to toxin producing bacteria (diphtheriae, clostridium tetani, bordatella pertussis) -

How do the subunit create immunity?

toxins are -chemically detoxified to toxoids - Retain immunogencity - work by the stimulating antibody response - Antibodies neutralise the toxins

How does tetanus antibodies get rid of tetanus infection?

- Pre-formed high affinity IgG antibodies can neutralise the toxin molecule in the circulation - the immune complexes are removed via the spleen - anti-toxins can also be given in established cases

What are the components of subunits vaccines?

-Thick polysaccharide coats of streptococcus pneumoniae and Neisseria meningitidis makes them resistant to phagocytosis

How are the vaccines of the subunit vaccines formed?

Vaccines for these organisms formed of purified polysaccharide coats- aim to induce IgG antibodies that improve opsonisation

What are the disadvantages of the subunit polysaccharide capsules vaccines?

- suboptimal as polysaccharides are weakly immunogenic | - no protein/peptide so no T cell response

How does the response improved fro polysaccharide capsule?

-utilise vaccine conjugation to boost response- protein carrier attaced to the polysachharide antigen

how does Subunit vaccines: polysaccharide capsules initiate immune response?

- Vaccine conjugation - Naive B cell expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate - Conjugate is process in the class II pathway - Naiive B cells presents peptides from the conjugate to T helper cell with the correct receptor - T cell helps the B cells to perform affinity maturation, but antibody is specific for the polysachharide and the for the protein conjugate

How does the Recombinant protein subunit vaccine work?

- Knowledge of key immunogenic proteins required - Protein expressed in lower organism - purified to produce vaccine - Hep B surface antigen - HPV vaccine

How is HPV vaccination created?

subunits are empty virus particles that prevent primary infection

what are the positives of using subunit vaccines?

- safe | - work well where primary infection may be prevented by antibody response

What are the negative of using subunit vaccines?

detailed knowledge required of virology specialised and expensive production -weaker immune response - booster required

what is the role of adjuvants in vaccines?

- boost immune response to antigen - Works by binding to pattern recognition receptors on antigen presenting cells - This enhance the co-stimulation and cytokine secretion which ensure robust B and T cell response

what are the novel adjuvants?

TLR ligands such CPG repeats

Explain mechanism for RNA vaccines?

- sequence generated which codes for critical pathogen to antigens - delivered via a vector - sequence translated by host cells to produce encoded antigen which stimulates host resposne

Explain the mechanism of DNA vaccines?

Use plasmid DNA that encodes vaccine antigen of interest - taken up by cells and transcribed and translated - elicits host immune response

what is one advantage and one disadvantage of using nuclear vaccination?

- advantage- only small amount of material is required | - Disadvantage: more safety concern due to nuclear uptake

Explain the how the viral vector is being used for creating vaccines?

Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens - Altered virus used as a live-attenuated vaccine - MERS spike proteins in small volunteers spiked a significant CD4 TCELL response and antibody response observed