Vaccines

• Passive immunity

  • Introduces components of the immune response (e.g., antibodies or stimulated immune cells) obtained from a donor directly into the patient.
  • Mother’s antibodies pass into the foetal bloodstream via the placenta–provides transient protection to the immunologically deficient newborn
  • Rabies is treated by passive immunity (human immunoglobulin is administered after bite to contain the virus before it spreads)
  • Has no memory short duration but rapid protection
• Active Immunity

  • Process whereby a person is made immune or resistant to an infectious disease, typically by the administration of a vaccine.
  • Vaccines are administered prophylactically to stimulate the patient’s own immune system to protect the person against infection or disease.
  • Gives long lasting protection (immune memory), has a lag time to develop protection
• How do vaccines work?

  • Vaccines consist of antigens that activate the immune system
  • Produce antibodies against the antigen
  • Induce immunological memory
  • Enable the immune system to recognise and kill specific pathogens when exposed a second time
• MALT

  • Mucosal associated lymphoid tissue
  • Collections of lymphoid cells or small lymphoid nodes found in the GI, urogenital and respiratory tracts
  • Contains M Cells that transport foreign material to lymphocytes in submucosa
  • In lymphoid nodes T and B cells interact following antigen stimulation and migrate to multiple sites in the submucosa
  • MALT is divided into segments depending on anatomical location
• MALT segments

  • NALT– Salivary glands and Waldayer’s ring (tonsils)
  • BALT– Lymphocyte aggregations located along the bronchial tree
  • GALT– Lymphocytes beneath epithelium along the entire GIT –Organised clusters in Peyer’s patches
  • Protects mucous membranes from pathogenic colonisation and infection
• Types of Vaccines

  • Whole organism vaccines include live attenuated and inactivated.
  • Non whole organism vaccines include subunit vaccines (polysaccharide, conjugate, recombinant protein), toxoid, mRNA, viral vector vaccines.
• Live attenuated vaccines

  • Live organisms
  • Undergo the process of attenuation
  • Reduces virulence
  • Maintains immunogenicity
  • Methods of attenuation: Classic attenuation or Genetically engineered attenuation
• Attenuated vaccines advantages:

  • Body does not distinguish between the natural pathogen
  • Vigorous and long lasting immune response
  • Usually only one immunisation required
• Attenuated vaccines disadvantages

  • Viral attenuated vaccines can mutate and revert back to virulent strain. Ex: Polio vaccine 1 in 2.5 million causes poliomyelitis
  • Can be transmitted to immunosuppressed individuals
  • Bacterial attenuated vaccines have relatively poor protection  compared with viral vaccines
• Classic attenuation

  • Passage through non-human cells (after being isolated from human cells)
  • Use of unusual growth media
  • Exposed to harsh chemicals
  • Loss of critical genes that cause virulence (over time)
• Gene deletion attenuated vaccines

  • Virulence gene is isolated
  • Removes virulent genes
  • Gene deletion
  • Targeted mutation
  • Resulting virus is viable and immunogenic but not virulent.
• Inactivated Vaccines

  • Organisms killed by physical (UV or Gamma irradiation) or chemical means (usually formaldehyde or β-propiolactone)
  • Eliminates ability to infect, but still immunogenic
  • Cannot revert to the virulent state
  • Examples: Salk polio virus, Pertussis, Influenza, Hepatitis A
• Inactivated Vaccines Advantages

  • Little risk (safe for immunodeficient pts)
  • Stable
  • Better immunogens than subunit vaccines

  Disadvantages

  • Not possible for all viruses

  • Not as effective as live viruses (first dose not sufficient)

  • May not protect for long periods (booster doses needed)
• Subunit vaccines pros and cons:

  • Safer Cannot reproduce or become virulent

  • Can use a single or multiple antigens

  • Often less effective than whole organism vaccines

  • Can be costly to produce

  • Always requires boosters
• Subunit vaccines

  • A viral surface protein or glycoprotein that gives protective immunity
  • Can be isolated from a virus
  • Influenza (hemagglutinin (HA) and neuraminidase (NA))
  • Can be made by recombinant DNA: Hep B vax made in Yeast cells and Hep B Surface antigen
• Toxoid Vaccines

  • Some bacterial pathogens produce exotoxins which can be the cause of the disease
  • These can be isolated and modified
  • Exotoxins are treated with iodine, pepsin, ascorbic acid or formalin which reduces the toxicity, but still immunogenic
  • On administration of the vaccine antibodies are produced against the toxoid
  • When challenged with bacterial exotoxin, antibodies bind to the exotoxin before they can reach the target cell
• Examples of Toxoids Vaccines

  • Diphtheria exotoxin produced by Corynebacterium diphtheriae causes the disease in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis
  • Tetanus exotoxin produced by Clostridum tetani is a powerful neurotoxin that blocks neurotransmitter release at the neuromuscular junction
• Conjugate Vaccines

  • Polysaccharides are major virulence factors but are poorly immunogenic
  • Do not elicit a T helper cell response to produce memory B cells
  • So they are conjugated to toxoids such as diphtheria toxoid (Pneumococcus vaccine) or tetanus toxoid (Haemophilus influenzae b) to increase immunogenicity
  • Used in routine paediatric immunisation
• Adjuvants

  • Macrophages, monocytes, neutrophils and dendritic cells recognise pathogen-associated molecular patterns (PAMPs) on the surface using pattern recognition receptors (PRRs) triggering an immune response
  • Highly purified vaccine components frequently lack PAMPs
  •  Adjuvants can act like PAMPs, triggering the innate immune response, to identify the vaccine components as a “threat”, with activation and maturation of APCs
• Adjuvant vaccine example

  • Shingrix® Herpes zoster used for Prevention of herpes zoster in adults aged 50 and older
  • Liposomal formulation based on MPL and QS-21 (plant extract)
  • QS21 can be toxic by binding to cholesterol punching holes in erythrocyte membranes.
  • The cholesterol in the liposomes blocks the toxic properties of QS21 as it binds to the cholesterol in the liposome bilayer rather than in cells 
  • Reconstitute antigen powder with adjuvant suspension before administering
• Vaccine Formulation Excipients

  • Added to prevent microbial contamination or to stabilise the vaccines or are remnants of the manufacturing process
  • concern for patients who may suffer from allergic reactions
  • gelatine- Protects vaccine from effects of heat and freeze drying (MMR, rabies, chicken pox)
  • Egg Albumin- some viruses are grown in embryonated chicken eggs; often carried over in influenza vaccine
  • Antibiotics- to prevent contamination during manufacture
  • MSG- preservative and stabilizer (Influenza, MMR)
• conventional vaccines

  • Can take months to produce
  • Grown in chicken eggs or mammalian cells
  • large quantities of virus for each batch
  • Bespoke production process needed with complex purification steps
  • The antigen or whole virus is injected
• mRNA vaccine comparison

  • One week to make an experimental batch

  The mRNA is made from a DNA template in the lab.

  • no virus needed (small q for sequencies/testing)
  • standardised production process
  • The RNA that encodes antigen is injected and the host cell manufactures the antigen