Convergent affinity maturation.

Antibodies are the first line of defense of our organisms against noxious substances. They are the proteins which we ‘train’ to recognize noxious substances when we get immunized. Therefore understanding the immune response after being presented with an antigen is instrumental in developing novel vaccines.

One hypothesis relating to immune response to an antigen is that different organisms are likely to raise similar or even identical antibodies against the same antigen. Testing this hypothesis has become more realistic recently with the advent of Next Generation Sequencing technologies (NGS). Using NGS techniques it is possible to interrogate the sequential makeup of a large set of B-cells.

Such a study was conducted not that long time ago by Trueck et al. They have analysed antibody repertoires of five individuals, pre and post immunization to check if the immune systems converged on similar antibody sequences. The five individuals were immunized with a conjugate vaccine of HiB, MenC and TT. The antibodies were sequenced from cells extracted pre-vaccination and seven days after vaccination.

Firstly, the antibody repertoire appeared to reflect the fact that an organism was mounting an immune response as the clonality post vaccination was higher than before vaccination (more cells producing similar antibodies). Secondly, authors focused on identifying sequences from the public repertoire — those antibodies that are shared between individuals. This analysis focused on the CDR3 only, of which 47 were shared between at least two of the five individuals. Quite a large proportion of those sequences were known to be specific towards HiB and the enrichment of these was muhch higher in the post-vaccination sample. Only one sequence in this set was known previously to target TT. Nevertheless, relaxing the sequence similarity condition, a lot of sequences related to those known to be TT-specific were found among the five individuals. Most importantly, the number of such sequences was much higher in the post-vaccination samples, indicating that these might indeed have been raised in response to TT stimulation. The same was not true for MenC as hardly any sequences related to this antigen were found in the immune response of the five individuals.

Therefore, authors claim that looking at the enrichment of such shared sequences can be an indicator of the effectiveness of the immune response. They correlate statistics coming from looking at the number of shared sequences which appear to have moderate correlation to the antibody avidity data (even though p-values in some cases are quite high). This indicates that even in such a small set of individuals, antibodies are capable of converging on similar solutions. This might provide clues as to the characteristics antibodies that recognize specific antigens and thus facilitate novel vaccine design.