Published on November 12th, 2020, by Labtoo's team
Using more or less attenuated pathogenic agents to protect a patient against an infectious disease is an ancient technique, but the concept of “vaccination” will only be fully acknowledged during the 18th century. Focus on the history and development of this peculiar therapeutic tool.
The early days of vaccination
The inoculation of vesicular pus from smallpox-infected persons to healthy people goes back to the 10th century: this process was called “variolation” and was initially performed in Asia before expanding throughout Europe. The diffusion of this new medical process is mainly permitted by numerous scientists and intellectuals from that time, such as La Condamine, Mary Montagu and Voltaire, although the technique in itself was also quite controversial.
Variolation poses risks to the patient, and the method is accused of causing epidemics. The controversy will persist until the 18th century; Edward Jenner, an English physician, develops at that time an innovative alternative by using a cowpox vaccine (primarily infecting cows) on humans to induce an immunity to smallpox. Indeed, Jenner observes that milkmaids who milk cows infected by cowpox do not develop smallpox afterwards. He theorizes that cowpox actually protects milkmaids from smallpox, and so decides to test that hypothesis on James Phipps, an eight-year-old boy, in May 1796. He inoculates vesicular pus to the boy, sampled from the hand of a cowpox-infected milkmaid, Sarah Nelmes. After introducing the pus on arms incisions, Jenner’s young patient develop a fever episode that do not last for a long time. James Phipps is then submitted to a variolation test by Jenner: no signs of infection are detected. The name “vaccination” (from vacca, cow in Latin) is used to designate this process of immunization.
Vaccination met a great success throughout Europe since the beginning of the 19th century, while variolation fell into disuse until its total proscription.
The creation of vaccines
Vaccination originally refers to the process of immunization developed by Edward Jenner ; it does not primarily include a “vaccine” in the modern sense of the term. Vaccines have been in fact developed at the end of the 19th century by Pasteur and other scientists.
By studying fowl cholera with Émile Roux and Émile Duclaux, Pasteur discovers that the inoculation of old strains of Pasteurella multocida to poultries does not induce death; on the contrary, it even strengthens their resistance to other infections. Immunization is triggered by inoculating attenuated virulent strains. Pasteur then looks after ovine and bovine anthrax, then swine erysipelas: while his vaccine production first meets a great success, some stability and efficacity issues tarnish his vaccines’ reputation, thus discouraging scientists to follow his steps.
Pasteur then shows his interest for human infectious pathologies, in particular rabies. He determines that the virus is found in higher quantities in the nervous system of infected animals, and not in their saliva. He manages to obtain a weakened form of the virus by exposing an infected rabbit’s spinal cord to dry air. In 1885, he uses his vaccine on Joseph Meister, a 9-year-old bitten by a rabid dog, who received 13 successive inoculations of weakened viruses. The experience is a success as Meister is found in good health. Although many will critic his work, Pasteur can be seen as a pioneer in vaccination; and it is after his research on rabies that he will establish the Pasteur Institute in Paris.
Discoveries on pathogenic agents and vaccines will happen all along the 19th century, mainly in France and Germany, historic cradles of the greatest microbiology schools. Émile Roux’s and Alexandre Yersin’s work on diphtheria allows them to isolate bacterial toxins. The discovery of antibodies and anatoxins will permit scientists to create inactivated vaccines (with killed pathogenic agents).
The 20th century will be a particularly fertile year in the field of vaccination, as vaccines against diphtheria, tetanus, tuberculosis, typhus and other infectious diseases will be developed at that time. The middle of the 20th century is marked by the discovery of antiviral vaccines, primarily directed against yellow fever, flu and poliomyelitis. Combined vaccines, which offer protection against several diseases in only one shot, will make their apparition in the 50s.
Vaccine production and delivery system
The progress made in biotechnologies and genetic engineering has greatly permitted vaccination to fully develop during the last decades. During the 80s, the vaccine against hepatitis B has been produced using recombinant DNA, thus leading to antibody production through virus-infected cells. Progress in artificial synthesis and research on bacterial capsule have led to vaccines made of substances derived from the bacterial envelope.
These numerous innovations in the field of vaccination have allowed their production technologies to rapidly evolve, although the fabrication processes are still very long and complex. Manipulating biological material necessitates heavy quality and security controls all along the fabrication. Producing vaccines globally involves two main steps: production of the active substance and production of the pharmaceutical form. Producing the active substance consists in producing an antigen that can be either an attenuated living germ or an inactivated killed germ/a toxin. This production process follows a globally defined pattern: germs cultivation and amplification, antigens extraction, purification and concentration, inactivation.
Producing the pharmaceutical form involves a formulation process (adding adjuvants, stabilizers, etc.), a sterilization stage, eventually a lyophilization stage, and then a packaging, control and batch release steps.
Vaccine administration has usually been traditionally performed with a syringe and a needle, but new delivery systems are on the way. We can find for example the jet injector (used for mass vaccination, especially during the 70s), implants, patches, sprays and oral vaccines, etc.
Endorsing both a preventive and therapeutic role towards patients, vaccination is one of the most efficient and economic sanitary acts to prevent diseases and associated complications, according to WHO. Vaccination has allowed to eradicate smallpox in 1980; and the mortality rate associated to pertussis, polio, diphtheria and tetanus reaches 0% in France. Currently, the Research and Development of vaccines experiences a significant turning point due to the COVID-19 pandemic. Public and private research structures are obtaining their first results for potential COVID-19 vaccines in a historical and never-reached-before record time.