Vaccine development has come a long way since the initial idea of inoculating someone with a disease to induce a response and result in immunity against the disease. Today a vaccine is defined as “a suspension of attenuated or killed microorganisms, administered for prevention, amelioration or treatment of infectious diseases.” The basic principle is to inoculate patients with a weakened pathogen and stimulating immunity by arming the immune system with the knowledge to fight the pathogen.
The idea of inoculation is thought to have originated in China, India and Africa as early as 1000 CE with the exponential outbreak of smallpox. The idea of a patient being “variolated” via administration of dried, crushed smallpox scabs taken from a mildly infected source via the nostril or through open wounds would lead to the patient developing a mild case and be able to recover fully. Although this did work in some cases, patients often died, particularly if given a live source accidently. Despite this, the idea paved the way for the development of the vaccine when brought to mainland Europe by Istanbul travellers during the 18th century, and was introduced to England due to the advocacy of Lady Mary Wortley Montague, who spread the prospect of inoculation throughout the country, planting the roots for the “vaccine”.
It was not until the Edward Jenner’s interest in the correlation between cowpox and smallpox, that a true vaccine was developed. Jenner had always shown interest in natural science, and whilst working as an apprentice developed an interest in the protective effects of cowpox against smallpox. It was known at the time that milkmaids who developed cowpox, would recover and not develop smallpox. Upon observation Jenner concluded that cowpox could be used as a protective measure against smallpox, whilst also being spread from one source to another as a protective mechanism. He put his hypothesis to the test in 1796 by inoculating a young James Phibbs with the matter from the pustules of a milkmaid who was suffering from cowpox.
127 our experts are availableright now
The boy fell ill for several days, recovered and was inoculated again with the matter of a fresh smallpox sore, and in correspondence to Jenner’s hypothesis the boy remained healthy. Jenner’s discovery lead to doctors eventually vaccinating their patients against this smallpox, and by 1800 it had spread to most of mainland Europe. The term was coined “vaccination”, as “vacca” was Latin for cow, and “vaccinia” for cowpox, of which the treatment was derived. Despite Jenner not actually formulating the principle of vaccination, he did confer a scientific status to the procedure that is so widely renowned today.
The next major development in the vaccine timeline was that of Louis Pasteur and the discovery of a rabies vaccination in 1885. Pasteur, following Jenner’s principle, injected viral rabies matter from infected dogs into the brains of rabbits. He then took the viral matter from these infected rabbits and injected a young boy who had been attacked by rabid dogs. The boy made a full recovery with no disease symptoms. Pasteur had actually weakened the virus by passing it through a series of hosts, hence resulting in an inability to reproduce in the original host. By doing this the virus was deemed “attenuated”, and to this day is the founding principle of administer “live attenuated vaccines”.
By 1900 there were 2 vaccines developed against human viruses, smallpox and rabies, and 3 against bacterial viruses including cholera, typhoid and the plague. With increasing research and interest many diseases that had been lingering and caused high mortality rates for centuries could be reduced greatly including the likes of many childhood illnesses such as mumps, measles, rubella, tuberculosis and polio. The most recent vaccine discoveries in the past 20 years include pneumococcal conjugate, and human papillary virus , with current attempts being put into place to develop a vaccine against the raging coronavirus COVID-19.
So, what is the active mechanism behind vaccines? Vaccines work by “imitating an infection”. Vaccines work by injecting pathogens into the body that bypass the innate immune system and activate the adapt immune system. When the microbe presenting the antigen is phagocytosed via macrophage or dendritic cells, the remaining antigen components are internalised, processed into epitopes and loading onto MHC molecules that are presented to T Helper cells. Upon recognition of the antigen, T Helper cells produce cytokines that activate B cells to proliferate, becoming plasma cells, some of which produce antibodies (immunoglobulins). Each epitope presented has a particular antibody that binds and inactivates it, thus preventing infection.
Some of these B cells are also instructed to become memory cells, cells that do not engage in the immune response but have a memory of the particular antigen and antibody produced. Should that antigen be presented again a faster, secondary response will be induced due to having knowledge of the correct antibodies from the “immunological memory” of the B cells, and ability to produce them immediately rather than waiting to find the correct one, resulting in disposal of the pathogen without infection. These antibodies help to also neutralize microbes by binding to the antigens, preventing binding to cell receptors and thus preventing entry to cells. As well as this, antibodies can induce the complement system (plasma protein assembled into a particular sequence) that form a membrane attack complex, resulting in lysis of the microorganism.
Overall vaccines amount a slow primary immune response upon initial pathogen introduction, due to antigen recognition being required, followed by correct antibody production (this process can take 4 to 7 days at least). However, upon repeated exposure a secondary immune response is initiated rapidly as the required antibodies can be produced via the existing memory cells. By using vaccines this immune response can be reproduced on a larger scale, without inducing infection, through administration of various treated forms of microorganism, thus inhibiting their ability to reproduce, but allowing recognition simultaneously.
There are several types of vaccine that can be administered to induce this “immunological memory”, consisting of 5 main types: Live attenuated, inactivated, toxoid, conjugate and subunit vaccines. Live attenuated vaccines contain microbes that have been treated to be less deadly, and so are the closest thing to a “natural infection”. These microbes, as living, result in strong immune responses however due to being living cannot be given to those that are immunocompromised due to their immune systems not being strong enough, examples include the MMR vaccine and varicella vaccine. Inactivated vaccines consist of microbes that have been killed before administration, fighting infection however producing a much weaker immune response.
Due to this, these vaccines often require “booster” shots in order to build up a sufficient immunity. Toxoid vaccines protect against toxins produced by microbes, not the microbes themselves. Inactive toxoid components are given in order to build an immune response. Conjugate vaccines fight against microbes that have an outer coating (such as polysaccharides that can mask the antigens) by joining the microbe to an immunostimulant such as adjuvants, to amount a larger immune response. Finally, subunit vaccines consist of only a “subunit protein” of the microbe, so once delivered the pathogen cannot replicate but can induce an immune response. Despite administration of vaccines, often they require booster or top ups in order to develop a strong enough immune response to prevent any form of microbial reproduction, and also for the likes of inactivated/toxoid sources the primary response is often weak and requires a second administration to mount a full response.
