Physicians have been using the basic principle of vaccination for centuries: They purposefully expose the body to a killed or attenuated pathogen, and the subsequently developed memory immune response prevents a more severe course of the disease following reencounter with the pathogen. Today, many vaccines consist of individual components of the pathogen, which are able to confer protective immunity, the so-called antigens. The resulting subunit vaccines display an improved safety profile; however, it is a challenge to achieve the same level of protection as with a complete pathogen. Therefore, many vaccines contain adjuvants that strengthen the vaccine response. The right adjuvant can also improve the protection provided by the vaccine for certain groups of people, because, as trivial as it sounds, "Not all humans are the same," says Prof Carlos A. Guzmán from the Helmholtz Centre for Infection Research (HZI). For example, only a small proportion of people aged over 60 develop sufficient protection after a standard influenza vaccination. Administering the vaccine together with an adjuvant such as an emulsion of oil and water, however, significantly increases vaccine efficacy.
Emulsions or aluminium salts have proven to be efficient and safe vaccine boosters. Carlos A. Guzmán and his team are now developing a second generation of adjuvants: They are using compounds produced by microorganisms that are able to stimulate the cells of the innate immune system and activate various defence mechanisms in the body. "For a vaccine to be effective, the combination of adjuvant and antigen must be adapted to the individual characteristics of the pathogen," says Guzmán. This is because pathogens have developed various strategies to resist human defences. Some evade the immune system, such as influenza viruses. These viruses constantly change their strongest antigens, making necessary the manufacturing of a new vaccine every season. Researchers are therefore attempting to create artificial antigens from stable components of the virus. Their vision: to develop a universal influenza vaccine based on these designer antigens.
Guzmán's team recently constructed in vitro a vaccine from several parts of various stable components of the parasite Trypanosoma cruzi. The single-cell organism causes myocarditis and has a sophisticated way of hiding itself from the immune system, meaning that neither a vaccine nor a cure has yet been developed. "Together with colleagues from Argentina we removed all the parts of the antigens that do not trigger the proper immune response and used only those that are necessary to generate protection," says Guzmán. The researchers combined their synthetic designer antigen with an adjuvant developed at the HZI, a second messenger substance derived from bacteria. The resulting vaccine activates the critical defence mechanisms needed to eliminate the hidden parasite. Thus, it is specifically tailored to the pathogen, thereby enabling to prevent infection by the single-cell organism. Structure-based antigen design and the use of well-defined adjuvants represent the vaccines of tomorrow: customised and efficient.
Author: Ulrike Schneeweiß
Published: May 2019
