Vaccines

• Defining Immunisation and Vaccination
• History of Vaccination
  • Relevance
  • History of Vaccination
  • History of Vaccine Trials

in work and incomplete

Defining Immunisation and Vaccination

Immunisation and vaccination are used here as follows:

Immunisation

Immunisation prepares the immune system prevents a disease and possible damage but not necessarily infection.

Vaccination

Vaccination teaches the immune system how to handle something.

• Vaccination can provide immunization i.e. to prevent a disease.
• Vaccination can also teach the immune system how to handle something in a ‘bad’ way in the sense that those vaccinated are at increased risk. The immune system is complicated, e.g. what may work for young can fail for old and vice versa.
• In literature vaccination is often used more specific e.g. “stimulating antibodies production against something harmful or the agent of a disease”. Here the more general usage, given above, is used since:
  • Immune Response: The immune system is more than antibodies. Many vaccines (especially live pathogen vaccines e.g. the oral polio vaccine) induce a broad immune response e.g. including immune cells supervising the right locations.
  • Specify the target: Some definitions use ‘something harmful’ or ‘the agent of a disease’. But many living organisms are part of the biome of healthy people and are just pathogens or agents of a disease in special situations. E.g. many viruses live in our respiratory tract or intestine and help to train the immune system. Just under specific circumstances they can become pathogenic e.g. when the immune system is suppressed. Are they know harmful or agent of a disease?

History of Vaccination

Relevance

The history of vaccination helps to understand vaccines and their design and success. The history also helps to understand the design of vaccine trial schemes geared towards live pathogen vaccines. The early vaccines just were live pathogens, while new vaccines methods were invented, the trial schemes remained largely unchanged - it is just “THE” way to check vaccines.

History of Vaccination

• Change of Infection Pathway: Purposeful immunisation is handed down from ancient China and India (likely densely populated regions) where smallpox was inoculated to the skin. This administration path still was quite risky though lower than inhalation to the lungs.
• Related Pathogens: In 1796 it was observed cowpox exposed people had an increased resistance to smallpox infection. To protect against smallpox from this point on cowpox was used.
• Attenuated Pathogens: After the success with smallpox, a vaccine research branch developed. Human pathogens were taken and adapted to different environments. Upon back-inoculation back to human the disease was milder compared to the original pathogen.

Even though successful, attenuated vaccines had drawbacks: from time to time the disease was caused, to exclude a disease the pathogens were inactivated:

• Inactivated Pathogens: The pathogens are inactivated e.g. by heat or UV light.

Inactivated pathogens not always work since the immune system may see no need for antibodies. To signal the immune system it should produce antibodies, adjuvants were introduced.

• Vaccine with Adjuvants: Immunogenic substances are added mixed with the antigens to increase the immune response.

History of Vaccine Trials

For live attenuated vaccines the main concern is, the disease to prevent is caused. Since the disease and its symptoms are usually known, the vaccines trials were designed to watch out for the symptoms (named reactogenicity). While not perfectly safe, attenuated vaccines usually are by a large margin safer than the original pathogen. New technologies came such as inactivated pathogen or pathogen protein vaccines but the trials design and safety assessment were largely unchanged. The new techs usually rely on adjuvants (some substance increasing the immune response e.g. aluminum is used). The trials in these settings are only adequate if the adjuvant safety profile is known (which is often not really the case except for short term symptoms). Due to the often unclear safety of the adjuvants, these new techs rather obfuscated than eliminated the risks. For many Covid vaccines once again new techs are used.

• The established vector based approach though experience with human was very limited and most experience was from farming animals. Which is taking some known viruses make them expressing some SARS-2 protein (the spike is used) replication incompetent but make them replication incompetent.
• The never before used transfected RNA approach. In which a codon optimised and nucleoside modified translatable RNA is encapsulated in some lipid envelope such that cells are transfected with the RNA. Some of the RNA then is translated like messenger RNA.

The vaccines were tested like any other vaccines constructed with established technologies: In large trials people were watched for symptoms. These may not be enough to ensure safety as discussed in [Safety Questions]