Vaccination

13 Oct 2020

Vaccination is acquisition of a specific response of the immune system to pathogens within the body. It is achieved by the introduction of a substance that will bring about an immune response. This then leads to immunisation to the pathogen. Immunisation is associated with lower incidence of disease in a population with reduced complications of disease when it does develop. Factors such as herd immunity can provide further protection to a population as the ability of a pathogen to propagate across a population is impeded by immune individuals. Immunity is commonly mistaken as binary, rather than highly variable over time. Comprehensive vaccination programmes greatly reduce the burden of disease on public health and can improve the average number of quality years lived in a population significantly.

Vaccines can degrade rapidly if not stored in correct conditions. This can render them ineffective when administered which poses a risk to health. Ensuring that the quality of a vaccine is not compromised means maintaining the cold chain from manufacture to administration. Different vaccines have varying sensitivity to heat and therefore different storage conditions; these different storage conditions can produce significant logistical issues to rolling out vaccination. Temperatures of storage areas must be monitored and there should not be any deviations from the defined temperature range. Some vaccines require very cold storage which in turn necessitates the use of expensive and uncommon freezers. In developing countries these issues are magnified. Even if a vaccine is highly effect it may be unfeasible for widespread use if the logistics of its supply and storage are too challenging. Consideration must also be given to the cost versus the risk of infection.

There are a few broad classes of vaccines:

• Whole pathogen vaccines
  • Live attenuated
  • Inactivated
  • Conjugate
• Toxoid vaccines
• Subunit vaccines
• Nucleic acid vaccines
  • DNA
  • RNA
  • Recombinant vector

Live attenuated vaccines

Live attenuated vaccines are live viruses or bacteria that have been weakened so that they generate an immune response but do not cause disease. They are often created by replicating the pathogen in cells that they do not typically infect for many generations. This leads to maladaptation of the pathogen to its intended host.

MMR vaccine is a combination vaccine which provides protection against infection with measles, mumps and rubella. These are serious diseases which can cause permanent disability and death. Three weakened live strains are included in the vaccine. It is given as two doses. The first is usually around one year of age; this is because maternal antibodies have subsided at this time which can render the vaccine ineffective by working against the active components of the vaccine. A second dose is given before the child starts school – typically at 3 years and 4 months old.

BCG vaccine is a vaccine against the bacteria that cause tuberculosis. It is not part of the NHS routine vaccinations but is given to people that are deemed as high risk. This can be due to a parent or grandparent being born in a country where there is a high rate of tuberculosis, or being born in areas of the UK where tuberculosis rates are higher than the rest of the country. The vaccine contains a live weakened form of the bacteria.

##Inactivated vaccines Inactivated vaccines are vaccines that are produced by producing a large number of the virus and then physically or chemically inactivating them. The whole ‘killed’ pathogen or parts of the pathogen, when introduced to the body, will induce the intended immune response. The vaccine for influenza is an example of an inactivated vaccine.

Influenza vaccine is given annually and is offered to at-risk groups and healthcare professionals. At-risk groups include the elderly and those that suffer from conditions that increase the likelihood of adverse effect from complications of influenza. Proteins that cover the surface of the virus are included in the vaccine and promote an effective immune response when the vaccinated person comes into contact with annual flu.

Conjugate vaccines

Some pathogenic bacteria have very poor immunogenicity and can be vaccinated against by conjugation of the bacteria with an antigen with greater ability to induce immune response. The pneumococcal vaccine is a conjugate vaccine that is given at 8 and 16 weeks of age with a further booster at 1 year. This will change to two doses given at 12 weeks and 1 year. This vaccine is also given to those over the age of 65 just once, unless they also have an underlying health condition. Typically a higher valent pneumococcal vaccine is given over the age of 65 which provides protection to a greater number of strains of pathogenic bacteria.

Toxoid vaccines

Toxins that cause diseases such as diphtheria and tetanus are purified and inactivated by chemical means. This disrupts the structure of the protein and its ability to cause symptoms in the individual. Two toxoid vaccines form part of the combination vaccine DTP.

Subunit vaccines

Recombinant protein vaccines Take the gene for the antigen and express it in something else. Harvest, concentrate and inject. Receptor binding domain vaccines Similar to recombinant protein but only involves the part of the antigen that forms a complex with human cells. Hep B and HPV vaccines

DNA vaccines

DNA plasmid grown in large quantities. Injected and electroporation utilised to get DNA into cell. When present in nucleus of cell protein is translated and expressed.

RNA vaccines

Encapsulate mRNA in lipid nanoparticles. This mRNA can code for just the antigen or it can be self-replicating and code for both the antigen and itself. Production is entirely in vitro which is good for scalability. However, storage requirements for these vaccines are typically -80C which presents a challenge for distribution.

Recombinant vector vaccines

Use another non-pathogenic virus to insert gene for desired antigen. This causes some cells in the vaccinated person to produce the antigen. May be replication competent or incompetent. Potential problems with pre-existing antibodies rendering the vector useless. Can be circumvented by using a virus that isn’t prevalent in humans. Advantage good T cell response due to activation of innate immune response. Disadvantage can prove problematic in those with reduced immune response. Ebola vaccine.