Vaccination is a fundamental pillar of human health. Yet our understanding of how the immune system recognizes pathogens is still quite limited. By combining computer science and immunology we are now beginning to decifer the language of immune cells.

Written by Rahmad Akbar, Victor Greiff, Milena Pavlović , Philippe Robert, Geir Kjetil Sandve, Lonneke Scheffer, Andrei Slabodkin, Igor Snapkov, University of Oslo.

Click here for Norwegian translation.

Vaccination rests on the property of the immune system to form immunological memory. The immune system remembers successful battles of the past to mount more efficient immune responses upon meeting the pathogen a second time. Just like our brain remembers many things from our childhood up to our present age, our immune system keeps a record of every infection it has encountered over the lifetime.

Immune memory is recorded in the most universal USB drive of all – the DNA. Most immune cells (called “adaptive” immune cells), each have unique sections of DNA. More precisely they are each programmed to recognize different targets . Our immune memory is a combination of those soldiers, that the body has selected and multiplied in previous fights.

A successful vaccine needs to wake up enough soldiers and train them to recognize a specific target.

Over the past 10 years, it has become possible to read the DNA of immune cells (called immune receptor sequencing). But reading the DNA of immune cells does not necessarily mean we understand how the DNA encodes immune memory. Just like a German may be able to read out loud a text in French (albeit with an accent), it does not mean they understand the text. Analogously, the record of past encounters with antigen is encoded into the DNA in a way that we currently do not really understand. While we do understand what each letter of the DNA means, we do not understand how a set of letters (or words) describe the memory of previous infections. If one could decipher how past immune battles are encoded into our immunological memory, then we would be able to design more effective vaccines.

Vaccine design is hard because we are designing vaccines for an entity, the immune system, which we don’t fully understand.

Recently, bioinformatics and machine learning have shown incredible success in identifying hidden patterns in very large sets of biological data (such as the DNA of immune cells). We and other research groups have begun to combine computer science and immunology (and even linguistics) to decipher the language in which the immunological memory is written. For instance, if the pieces of DNA from each cell are a sentence, it may be possible to identify common words that describe previous encounters with same pathogen. Computer analyses, in conjunction with the extraction of ultra-large datasets, may help write the next rosetta stone of immunology, which could help translate how our immune system keeps track of the myriad of bugs it has encountered throughout our lifetime (see Figure below).

For example, by using methods from evolutionary and mathematical ecology, we can now analyze how our immune system evolves over time in response to pathogen challenge, and get a glimpse at how the best immune soldiers are selected. Specifically, such studies serve to analyze how the immune system chooses which immune cells are recruited to form the memory cell pool (the elite veteran army). This will give us a better understanding of how we have to design more efficacious vaccines.

Research groups are also now looking into how our immune system detects foreign and potentially dangerous particles (called antigen) via the very detailed molecular resolution of immune-cell-antigen complexes at a subnanometer scale (1 million times smaller than a human hair). Such analyses seek to analyze how our immune system interacts with bacteria and viruses allowing us to see through the immune systems’ “eyes” – which, in turn, may provide an improved understanding of how to reverse engineer effective vaccines.

Finally, given that experimental datasets are scarce, we and others, have started to implement computational simulations of the immune system to test boundary conditions under which long-lasting and specific immune memory can develop. Computer simulations are becoming increasingly important in the biological sciences as they help sift through millions of different immune scenarios thereby speeding up immunological discoveries.

In conclusion, defending the body is not an easy task. Nevertheless, the body succeeds each and every day to fend off infections through the use of a very complicated immune language. Only thanks to new technologies and computer simulations, are we able to read millions of such words. Now remains the task of understanding their meaning. Extracting patterns with machine learning and language processing tools is a promising approach to pin down the natural language of our immune defense. If we are successful, the discovery and production of new vaccines can become an easier dialog.

Finally, to get an impression of how much of an impact vaccination has had on public health, take a look at this short video: