In 1796, the British country doctor Edward Jenner conducted a daring experiment: Based on the observation that milkmaids who had been infected with cowpox (a mild cattle disease in humans, also known as milker’s nodules) did not fall ill with the “real” smallpox (a widespread infectious disease at that time, which killed about 30% of patients), he took material from a cowpox pustule on the hand of a dairy maid and used it to vaccinate an eight-year-old boy. About six weeks later, Jenner exposed the boy to highly infectious smallpox pus – and the boy proved to be immune. This experiment, which may seem ethically questionable from today’s perspective, was the beginning of an incredible medical success story. Vaccinations are now among the most effective and safest preventive measures in medicine. With the help of worldwide vaccination campaigns, some infectious diseases have been almost eradicated, especially in industrialized countries – the world was declared smallpox-free by the WHO in 1980, and the global eradication of poliomyelitis (polio) is the next realistic goal.
Vaccination thus serves the preventive (prophylactic) protection against transmissible diseases. The principle of vaccination has not fundamentally changed since Edward Jenner. It involves either vaccinating a person with a weakened (= attenuated) pathogen (exactly what Edward Jenner did in the 18th century with the cowpox pathogen) or – the more modern approach – only components of a pathogen are vaccinated. By dealing with either the complete pathogen or its components, our immune system responds, ensuring future protection against infection with the actual pathogen – we also refer to this as the pathogenic wild-type pathogen –.
A crucial aspect is that the immune response of our body leads to the formation of highly specific antibodies – we also refer to this response of the immune system as the so-called humoral immune response. The antibodies formed during the humoral immune response are capable of neutralizing and eliminating microorganisms before they can cause an infectious disease in the body. This is exactly why it is not so trivial to develop an effective vaccine – a simple response of the immune system is not enough, the quality of the immune response matters. Vaccines must be able to produce a high-quality immune response in the body, which is accompanied by the formation of high-affinity antibodies and the training of memory cells, so that we can immediately form effective antibodies again upon renewed contact with the pathogen. This is also the challenge facing vaccine manufacturers in developing a corona vaccine.
The most effective vaccines consist of intact microorganisms (as in the case of Edward Jenner and cowpox), which are attenuated in the laboratory so that they can no longer cause disease but still lead to a complete activation of the immune system. Thus, viral attenuated (weakened) vaccines lead to a long-lasting specific immunity, so that for example the vaccination of children with the measles vaccine, which consists of attenuated measles viruses, provides lifelong immunization.
However, these effective live vaccines, which consist of attenuated viruses (= so-called live vaccinations), also have special safety aspects. For example, the weakened oral polio live vaccine (Sabin vaccine), which significantly helped to contain polio in the last century, has in very rare cases led to vaccine-associated polio (a disease similar to polio). Nowadays in Europe, this problem from the early days of polio vaccination is avoided by vaccinating with inactivated viruses (Salk’s dead vaccine). Incidentally, this principle is also applied for the annual flu vaccination – here too, inactivated (killed) influenza viruses are vaccinated.
Another important strategy to circumvent the safety concerns associated with attenuated microorganisms is that new generation vaccines often only contain components (antigens) of the microorganisms. Nowadays, in vaccine research, the most immunogenic microbial antigens are identified and produced in large quantities using recombinant DNA technology. In this way, the synthetic antigens can be used as vaccines. The vaccine against the hepatitis B virus or the human papillomaviruses (HPV), the pathogens of cervical cancer, are based on this technology.
To ensure that the immune system also adequately responds to the antigens, these are vaccinated together with certain adjuvants, which additionally stimulate the immune system – these are substances such as aluminium hydroxide gel or squalene. There are numerous myths about adjuvants, which are either simply wrong or refer to substances that have not been used for decades. The fact is that in modern vaccine research a lot of energy is put into the development of safe and effective adjuvants and modern vaccines have therefore become increasingly better and more tolerable.
