That micro-organisms have a great capacity to vary their surface structure is well known. It is one of the reasons why it is so difficult to develop vaccines against HIV and malaria, and why new influenza vaccines have to be produced every year. But it seems that these micro-organisms are also able to completely avoid activating a strong immune response in the person attacked.
This is what Professor Gunnar Lindahl from Lund University and his research group show in an article in Cell Host & Microbe.
"If we get a serious streptococcus infection, we want our immune defences to create antibodies aimed at certain parts of the micro-organisms' surface protein. But that mechanism does not work particularly well, which is a disadvantage for us and an advantage for the bacteria," he says.
Gunnar Lindahl's group has studied group A streptococci. These are one of the world's most important disease bacteria, causing ordinary tonsillitis, fatal toxic shock syndrome and a very serious autoimmune disease.
The part of the bacteria that has been studied is a surface protein called the M protein, more precisely the part of this protein (the "hypervariable region") which has the ability to vary extensively, in order to escape attack. The research showed that the relevant part of the protein was not just variable, but also managed to avoid eliciting any strong antibody response from the immune system.
"This may be what actually constitutes the micro-organisms' primary weapon: that they avoid antagonizing the immune system. In the case of a long-lasting infection, the immune system does indeed start to produce antibodies eventually, but by then the micro-organisms can have established a firm footing," says Gunnar Lindahl.
The micro-organisms' ability to sneak under the immune system's radar, as it were, was already suggested in certain scientific articles in the 1950s. But this ability was then overshadowed by their other defensive mechanism, i.e. the ability to vary their surface structure. And since a strong variation was considered to be obviously connected to strong antibody pressure -- that the micro-organisms were simply forced to vary in order to elude the antibodies -- no one has paid any attention to investigating whether there really was any strong antibody pressure.
The findings of the Lund researchers are part of basic research in molecular biology, but have consequences for the development of new vaccines. The vaccine developers must in future take account not only of the capacity for variation in bacteria, viruses and other micro-organisms, but also of their ability to avoid activating the immune defence system.
- Jonas Lannergård, Mattias C.U. Gustafsson, Johan Waldemarsson, Anna Norrby-Teglund, Margaretha Stålhammar-Carlemalm, Gunnar Lindahl. The Hypervariable Region of Streptococcus pyogenes M Protein Escapes Antibody Attack by Antigenic Variation and Weak Immunogenicity. Cell Host & Microbe, 2011; 10 (2): 147-157 DOI: 10.1016/j.chom.2011.06.011
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