Katharina Lahl

Fundamental biological knowledge is essential for better vaccines

Tuesday 19 Jan 21

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Katharina Lahl
Groupleader, Associate Professor
DTU Health Tech
+45 35 88 68 49

We have talked to Associate Professor Katharina Lahl, head of the research group “Mucosal Immunity to Viruses” at DTU Health Tech, about her research, in which she investigates the fundamental biology behind immune responses to get a better understanding of the basal requirements for better vaccine development.

Why do you work with fundamental biological questions?

These days, vaccines and viruses are very much at the top of people’s minds. To be able to develop effective and safe vaccines, detailed knowledge on the drivers of our immune system is crucial. 

By doing fundamental research on the biology of immune responses, we are expanding our understanding of how an immune response is initiated. One of our aims is to define what triggers our immune system to fire and how to engage the specific cells needed to fight a given disease. 

What is the interesting part of our immune system?

Our immune system is very complex, but what we do know is that various cells in the immune system respond to different triggers, and generally respond in a unique, very specific way. This means that when we develop vaccines, we want to make them as specific as possible, taking into consideration how to best tickle  the cells that yield the best protection. 
Even in many of the infectious diseases we see, the symptoms people experience during illness are largely caused by the immune system. When you feel ill, it is actually the immune response to the virus or bacteria rather than the infection itself that makes you feel bad. Therefore, good vaccines should be as specific as possible and target the precise cells required to battle the disease in question to avoid a more general and unpleasant immune response. 

In my team, we investigate which exact signals the immune system needs to  eliminate a specific virus. We specifically look at the dendritic cells in the mucosal layer of the intestinal walls and the lung, as those cells are crucial for initiating the immune response. Dendritic cells are the only type of cells that can pick up pathogen-derived signals and communicate to the rest of the immune system to start fighting the intruder. 

Our work is based on the assumption that different subsets of dendritic cells have different purposes, e.g. one subset is particularly good at inducing immune response to tumours and viruses, while another is better at recognizing many of the common bacterial infections. However, in a recent study we found that things are not as simple as that, as these subsets also influence each other. Dissecting which dendritic cell does what when will allow us to then engineer specific targeting strategies using that knowledge. Along those lines, we recently discovered a specific role for one subset in inducing antibodies towards rotavirus, a finding that we are excited to expand upon.

How will this affect society at large?

We are concerned with the role of dendritic cells in response to Respiratory Syncytial Virus (RSV), a lung-infecting virus, and rotavirus, which is an intestinal virus. There is need for better vaccines for both viruses. Rotavirus still kills  thousands of infants each year in developing countries as the existing vaccines, despite working really well here, are much less efficacious in those areas, a phenomenon that we do not fully understand yet. For respiratory syncytial virus, which is the leading cause of severe childhood respiratory infections world-wide, we do not even have an approved vaccine. Cheap and effective vaccines protecting from these two viruses would significantly lower the rate of childhood mortality caused by infectious diseases. More generally, since we focus on fundamental aspects of how the immune system works, our work also has a strong potential to contribute to solving open research questions concerned with other diseases driven by too much or too little immunity.

What do you hope to achieve? 

My goal is to better characterize subsets of mucosal dendritic cells and their role in the induction of pathogen specific antibody responses.  I am driven by the hope that our findings regarding immune recognition at mucosal surfaces will have a significant impact on both vaccinology and allergology. 
There is a lot we do not know about our immune system, but we are taking small incremental steps at the time to increase knowledge about how our body works. This knowledge is important to be able to design effective vaccines with the least side effects.

Achieving the task of making better vaccines is a complex and interdisciplinary endeavor. Health technological insights combined with biological knowledge and disease understanding is crucial for developing the vaccines of the future. You could say that we (biologists) provide the health engineers with input as to what defines a good vaccine. 

Photo caption: Associate Professor Katharina Lahl  (Photo by Jesper Scheel)

 

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https://hypermag.dtu.dk/news/Nyhed?id=%7B254E5BC7-6C6E-40D7-BF17-44A4AEB6CDD9%7D
3 MARCH 2021