Lecture 9 - Vaccinations Flashcards
Describe what is passive immunity?
-Without an active host response on behalf of recipient
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
what is recommended if a pregnant woman has no history of chickenpox and bloods are VZV IgG negative?
VZV immunoglobulin
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
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
How do most vaccines work?
generate long-lasting, high affinity IgG antibody response
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
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
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
Which vaccines are live but attenuated?
- Prolonged culture ex vivo in non-physiological conditions
- MMR
- Polio
- BCG
- Chloera
- Zoster
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
What are cons of the live vaccines?
- storage problems
- short shelf life
- may revert to wild type
- immunocompromised recipients may develop clinical disease
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
What happens when the viral infection is reactivated?
- Zoster infection
- Particularly elderly and fairly debilitating and may cause neuropathic pain
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
What is polio caused by?
- Enterovirus establishes infection oropharynx and GI tract
- spreads to the peyers patch then disseminated via lymphatics
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
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
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
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
