7. Vaccines Flashcards
Immunisation
Artificial process by which an individual is rendered immune
Passive immunisation
No active immune response in the recipient
Protection is temporary
-due to no memory cells
Active immunisation
Aka vaccination
Recipient develops a protective adaptive immune response
VZV in pregnancy
VZV during pregnancy can cause fetal complications
Exposure is treated immediately with vaccine
Indications for vaccine: VZV IgG negative or equivocal
Components of a vaccine
Antigen
Adjuvants
- increase immunogenicity of the vaccine
Excipients
-Increases vaccine integrity (ie various dilutents and additives)
Live-attenuated vaccines
Give examples
Live\weakened organisms
Organism are cultured to live in non-physiological conditions so that it is unable to cause disease
E.g measles, mumps, rubella, BCG
Pros and cons of live vaccine
Repeated boosting not required
Intracellular response leads to good CD8 response
Replication occurs within host
Cons
-May revert to wild type
- Storage problems- may revert to wild type
- Immunocompromised pts may develop disease
Inactivated vaccine
Entire organism used, but physical or chemical methods used to destroy viability (e.g. formaldehyde)
E.g. Influenza, Hep A
Subunit vaccines
Uses only critical part of the organism
- Toxins are detoxified to become ‘toxoids’
e. g Tetanus vaccine, Hep B, HPV
General Principals of vaccination
Most generate a long lasting high IgG antibody response
Most effective are when natural exposure leads to protective immunity
Varicella-Zoster Vaccine
Primary infection = chickenpox
Cellular and humoral immunity provide lifelong protection, but viruses establishes permanent infection of sensory ganglia
Viral reactivation=zoster
Particularly elderly, fairly debilitating and may cause long-term neuropathic pain
VZV vaccine
Live attenuated
-Induces anti-VZV antibodies
95% effective at preventing chickenpox
3-5% post-vaccination varicella infection
Zoster vaccination
- Similar to VZV vaccine, but higher dose
- Boosts memory T cell responses to VZV
Poliomyelitis (polio)
- Enterovirus causes infection in oropharynx and GI tract (alimentary phase)
- Spreads to peyers patches then disseminated via lymphatics
Haematogenous spread
1% develop denervation and flaccid paralysis
Tb infection
- During primary infection, MTB establishes infection within 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 (Ghon focus)
Most TB thought to be re-activation of this primary infection
Tb vaccination
BCG- intradermal injection
Aims to increase Th1 (IFN-g) cell responses to M bovis, conferring protection against MTB
80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB
Pros and cons of killed (inactivated) vaccines
No potential for reversion
Safe for immunocompromised
Stable in storage
Cons
- Mainly CD4/ antibody response
- Responses less durable then live vaccines
- Generally boosters required
- Higher uptake generally required to achieve herd immunity
Influenza vaccine
Protective antibody responses largely directed against Haemagglutinin and Neuramidase (external antigen)
Difficulties: antigenic shift
Tetanus vaccine
-Pre-formed high-affinity IgG antibodies can neutralise the
toxin molecules in the circulation; the immune complexes
are then removed via the spleen
-Anti-toxin can also be given in established cases (passive immunisation)
Polysaccharide capsules
- Thick polysaccharide coats of Streptococcus pneumoniae and Neisseria meningitidis make them resistant to phagocytosis
- Vaccines for these organisms formed of purified polysaccharide coats
- Vaccines formed of purified polysaccharide coats; aim to induce IgG antibodies that improve opsonisation
Vaccine conjugation
Naive B cell expressing surface IgM recognises polysaccharide antigen. Antigen is internalised together with the protein conjugate
Conjugate is processed in the class II pathway. Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor.
T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate
HPV subtypes commonly associated with cervical cancer
16 and 18
Pros and cons of subunit vaccines
Extremely safe
Work well where primary infection may be prevented by an antibody response
Works when the virus cannot easily be cultured eg HPV and Hep B
Cons
Development requires detailed knowledge of virology, pathogenesis and immunology
Specialised and expensive production
Weaker immune responses – boosting often needed and response rate varies
Examples of subunit vaccines
Hep B
HPV
Tetanus
