one hand, harmless and ubiquitous bacteria, other dangerous pathogens, the institutions suddenly attacked and one million children annually . Kill A current GEN-AU project deals with the mysterious interaction between streptococci and immune defense. The aim is affordable vaccines with as universal effect.
streptococci and pneumococci are one of the show the "dark side" of these normally harmless bacteria. Pneumococcal infections cause approximately one million deaths annually in children, more than 90 percent of them in developing countries. About the organization PATH, the Gates Foundation funded 60 percent of development costs, both in preclinical research as well as completed a few months, "Phase 1 study. This is the first time the safety and tolerability of the new vaccine tested on humans, and that in thirty healthy men. The data are not yet published. According to Nagy, the results were very encouraging. ". The vaccine proved so far to be safe and immunogenic" Now is already the roadmap for how to proceed - debate on the organization of large pivotal trials in Africa to market. To the finished product, it is still a long way.
to know-how, which brought the established ten years ago Intercell in this project and continuously brings in, with, within the scope of GEN-AU supported by strong experimental research project, the exploring the mechanisms and modulation of the immune system when exposed to various types of streptococci as its goals. With funding almost 250,000 € program started two years ago and runs until early 2012. Key partners of Intercell are two other institutions on campus that are part of the Max F. Perutz Laboratories, and the team of Beatrix Grubeck-Löwenstein by the Institute for Biomedical Aging Research in Innsbruck. So far, already several interesting publications resulting from the collaboration.
Nagy sees the promotion of basic research as the basis for many other programs, which are subsequently formed from the generated data. Above all, should be tried, the many details the cellular immune response when exposed to the pneumococcal antigens in the vaccine to explain. The
Intercell vaccine differs from the conventional products in several ways. The vaccines currently on the market protect against 10 or 13 of the 90 pneumococcal serotypes. Because the bacteria but always seek to escape the immune system, they variierien the code of their virulence factors. Once there is an immune response, the bacterium is able to change the sequence of this antigen and they can leave in the wake of the immune system. From the pressure of vaccination on the immune system develops in here Replacement effect that favors those bacteria that change their code. And this is already happening. In fact, already new vaccines against serotypes 15 and more in development. "It would be far too complex to couple more than 20 antigens to proteins," said Nagy. "There This approach is therefore a certain technological limits."
A vaccine against all pneumococcal
With an in-house developed genomic technology to identify suitable vaccine antigens she scanned with her team, so all 2000 proteins of the pneumococcal their suitability as a target for the vaccine. This was first serum collected from patients recovering from pneumococcal disease. "We the antibodies from the serum isolated and saw that antigens of the pneumococcal immune system that controls during the illness, "said Nagy. Following this example, the antigens were selected for the vaccine. In the end, there remained three.
These three proteins play an important role in the multiplication of bacteria. They are needed for the cell wall of bacteria during the division rebuild. "We have a completely new type of vaccine antigens found," said Nagy. This one was no longer as reliant as in the conventional pneumococcal vaccine on the virulence factors. "So we have a target selected, the very stable and at the same time in the life cycle of the bacteria plays a key role. "This provides a theoretical efficacy against all pneumococcal serotypes and hence an ideal suitability for developing countries, where very different serotypes prevalent than in Europe or the USA.
novel mode amplifier "IC 31"
is essential for the effectiveness of the adjuvant used in vaccines is always an active amplifier boosts the immune response to antigens. Here, too, Intercell is building with the new fully synthetic adjuvant IC-31 new to a technology that over the previously used mainly aluminum-containing adjuvants clear advantages added. While pushing these auxiliaries used in decades rather the formation of antibodies, IC-31 induces primarily a cellular immunity. "We know from clinical research, especially that associated with pneumococcal disease in these T-cell response in the form of Th17 cells is of paramount importance," says Nagy. "The Adjuvant IC-31 triggers in fact made such a strong immune response that it might even be possible to eliminate an infestation of pneumococci and to make the colonization reversed." In comparison, the functioning of the antibody response significantly more slowly because it takes several days for production here in the swing comes. In a violent situation such as infection in some African countries, but which could be a matter of life or death.
Whether the vaccine can even be used therapeutically, is currently, according to Nagy still uncertain. "We will see if it is possible to eliminate the bacteria, when the children are already colonized." Of these, it also depends on whether it would be theoretically possible to sterilize the body completely and permanently repel pneumococci. "But it may be that it's not desirable," says Nagy, "because they already belong to the child's flora." One possibility would be to reduce the bacteria count, and to maintain a lower level. ". Then would the likelihood that they swarm out and make as ear infections, pneumonia or meningitis reduced,"
antibiotics make pneumococcal aggressive
the principle question remains in all these diseases, why these bacteria swarm at all, and suddenly seized institutions or go into the blood?
are given there is still no definite answers but at least some theories, said Nagy. This suggests that the bacterial load, a role that would collect a human. The more bacteria, the more difficult it is for the immune system to control it. If in addition a viral coinfection occurs, as is very common especially in children, the bacteria can more easily penetrate normally sterile tissue.
"Finally," said Nagy, "there are certain lines that are more virulent than others." This also carry antibiotics for her part. Increase the virulence factor of bacteria and they are aggressive in the sequence. One can, warns Nagy, pneumococcal So wake up even a really well-intentioned therapy and exercise peaceful colonists to malignant disease-causing agents. The ridge is narrow.
And this phenomenon, it also applies to future vaccines to be observed. So dangerous rage, the bacteria can so devastating can be the counter-attack the immune system. From the great influenza pandemic in the winter of 1918-19 war, we know that most of the deaths were not caused by the virus and subsequent bacterial infections, but from an atypical violent reaction of the immune system. Vaccination may therefore not raise the spirits. "So far we saw only very mild curves," said Nagy is optimistic.
This article appeared in the latest issue of the journal genosphären . See also the related interview with Eszter Nagy.
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