Lecture 9 - Vaccinations Flashcards

1
Q

Describe what is passive immunity?

A

-Without an active host response on behalf of recipient

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2
Q

How are passive vaccines prepared and examples?

A
  • 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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3
Q

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

A

VZV immunoglobulin

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4
Q

What is active immunisation?

A

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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5
Q

What is herd immunity?

A

-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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6
Q

How do most vaccines work?

A

generate long-lasting, high affinity IgG antibody response

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7
Q

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

A
  • 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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8
Q

what goes into a vaccine?

A
  • 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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9
Q

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

A

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

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10
Q

Which vaccines are live but attenuated?

A
  • Prolonged culture ex vivo in non-physiological conditions
  • MMR
  • Polio
  • BCG
  • Chloera
  • Zoster
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11
Q

what are the pros of the live vaccines?

A
  • 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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12
Q

What are cons of the live vaccines?

A
  • storage problems
  • short shelf life
  • may revert to wild type
  • immunocompromised recipients may develop clinical disease
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13
Q

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

A
  • Chicken pox
  • Cellular and humoural immunity provided
  • Life long protection but virus establishes permenant infection of sensory ganglia
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14
Q

What happens when the viral infection is reactivated?

A
  • Zoster infection

- Particularly elderly and fairly debilitating and may cause neuropathic pain

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15
Q

how VZV vaccine work?

A
  • 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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16
Q

What is polio caused by?

A
  • Enterovirus establishes infection oropharynx and GI tract

- spreads to the peyers patch then disseminated via lymphatics

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17
Q

what are the possible complications of polio?

A

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

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18
Q

Compare Sabin oral polio vaccine vs Salk injected vaccine?

A

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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19
Q

What happens during TB infection?

A

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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20
Q

What is the vaccination for TB and how is produced?

A

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
21
Q

what does inactivated (killed) mean in vaccines?

A

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

22
Q

How does the inactivated trigger an immune response?

A
  • stimulates B cells
  • taken up APC cells to stimulate CD4 T cells
  • response less robust compared to live-attenuated vaccines
23
Q

Give examples of inactivated vaccines?

A
  • Hep A

- Influenza standard

24
Q

What are the advantages of using inactivated vaccines?

A

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

25
Q

What are the possible disadvantages of using inactivated vaccination?

A
  • Weaker response compared to live vaccination
  • No CD8 response therefore response less durable
  • Boosters required
  • Higher uptake required to achieve herd immunity
26
Q

What is influenza?

A
  • Seasonal viral illness

- protective antibody response against: Heamagglutinin and neuramidase antigen

27
Q

Why do we have to get influenza vaccination every year?

A

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

28
Q

What is antigenic shift?

A

when virus recombines with animal influenza strain

29
Q

How are the influenza vaccination made?

A
  • Virus grown in hen eggs

- killed vaccine is standard in UK

30
Q

what are the features of the sub-unit vaccines?

A

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

31
Q

Name some of the vaccines that are produced using subunits?

A

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

32
Q

How do the subunit create immunity?

A

toxins are -chemically detoxified to toxoids

  • Retain immunogencity
  • work by the stimulating antibody response
  • Antibodies neutralise the toxins
33
Q

How does tetanus antibodies get rid of tetanus infection?

A
  • 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
34
Q

What are the components of subunits vaccines?

A

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

35
Q

How are the vaccines of the subunit vaccines formed?

A

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

36
Q

What are the disadvantages of the subunit polysaccharide capsules vaccines?

A
  • suboptimal as polysaccharides are weakly immunogenic

- no protein/peptide so no T cell response

37
Q

How does the response improved fro polysaccharide capsule?

A

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

38
Q

how does Subunit vaccines: polysaccharide capsules initiate immune response?

A
  • 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
39
Q

How does the Recombinant protein subunit vaccine work?

A
  • Knowledge of key immunogenic proteins required
  • Protein expressed in lower organism
  • purified to produce vaccine
  • Hep B surface antigen
  • HPV vaccine
40
Q

How is HPV vaccination created?

A

subunits are empty virus particles that prevent primary infection

41
Q

what are the positives of using subunit vaccines?

A
  • safe

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

42
Q

What are the negative of using subunit vaccines?

A

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

43
Q

what is the role of adjuvants in vaccines?

A
  • 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
44
Q

what are the novel adjuvants?

A

TLR ligands such CPG repeats

45
Q

Explain mechanism for RNA vaccines?

A
  • 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
46
Q

Explain the mechanism of DNA vaccines?

A

Use plasmid DNA that encodes vaccine antigen of interest

  • taken up by cells and transcribed and translated
  • elicits host immune response
47
Q

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

A
  • advantage- only small amount of material is required

- Disadvantage: more safety concern due to nuclear uptake

48
Q

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

A

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