Professor Karin Loré calls the shots

Vaccination is something most individuals in Sweden are familiar with, most likely already at a very young age. Within the national vaccination plan eleven different diseases are included and during 2017 varicella may become added to that list. Each disease included is serious or has serious consequences, but thankfully today they are very rare as a direct result of vaccination efforts. When someone is vaccinated a dose of live attenuated or killed virus or bacteria is injected and the immune response reacts by producing antibodies that will protect if the individual is exposed again to that particular microbe in the future. Vaccine is protective both for the individual but also for the population as a whole, since vaccinated people do not spread the disease. Therefore, People who for different reasons are not vaccinated will thus be indirectly protected by the so-called herd immunity.

Foto: Ulf SirbornKarin Loré is a Professor in vaccination immunology and her research focuses on developing safe and effective vaccines. Her PhD studies concerned dendritic cells and HIV. “During my time as a PhD student new differentiation systems of these cells developed, which made the research within the field take off. It was hectic times but also very educational”. Karin continues: ”After my dissertation I was recruited as a postdoc by my opponent to a recently developed center for vaccination research at NIH (National Institutes of Health, Maryland USA). I noticed that the fact that my PhD education at Karolinska Institutet included personal involvement at every step of the research made me well prepared and self-directed enough to tackle the postdoctoral studies. It was more of a ‘sink-or-swim’ mentality at NIH, you are supposed to be driven by your own motivation,” Karin says.

The way to independence
Karin stayed afloat. Since her postdoc mentor was a T cell immunologist, Karin got full authority to set up a new sorting system for human dendritic cells. She then used these to study how to improve the function of dendritic cells with different vaccine components. After her postdoc period Karin returned to KI where she started her own research group. She implemented the same sorting system at KI and used this to study HIV vaccination in collaboration with Gunilla Karlsson Hedestam. In 2011, Karin received a relocation grant from Vinnova which allowed her to move back to NIH, this time as a visiting scientist with her own research group. During the following three years Karin focused on mapping the immunological process occurring directly after injecting a vaccine, the area which since then has been her main research focus. When the needle is inserted into the muscle and the vaccine injected, what is the immediate effect locally and systemically? Which cells are initially activated? Which ones are recruited and how do they interact with the vaccine on site? What is the role of the dendritic cells? Karin was looking for answers to these questions about what is happening in order for the body to build the immunological response protecting from a certain disease.

In 2014 Karin was appointed Professor at KI and returned with her research group. The same year she became group leader at CMM. The research conducted by the group has a translational approach from cells to models aiming for clinical studies. “You really need to have strong and convincing data before you are allowed to test a vaccine in humans. Vaccination is a prophylactic treatment for healthy people, many of them children, making the regulatory system around scientific proof and security precautions very strict.

Developing a powerful and safe vaccine
It takes a long time to develop a vaccine and one of the most challenging parts of that process is to identify and produce the right antigen to vaccinate with. The HPV vaccine (human papilloma virus that causes cervical cancer) is an example of a vaccine that has been very successfully developed. It only took approximately 25 years from identification of the antigen to an approved marketable vaccine. The HPV virus is also one of the viruses that are considered as being highly conserved, while in contrast the influenza virus mutates each year and the HIV virus is constantly mutating, which is one of the main reasons that it is so challenging developing effective vaccines. Thus there is a need for a broad spectrum of experts involved in vaccine development. Some research groups work with the understanding of which disease specific antigens to use, others focus on the strategy to produce stable antigens. Furthermore, as industry is responsible for manufacturing regulatory requirements and quality assurance, immunologists such as Karin’s group can study the immune responses of the vaccines manufactured. Experts at the public health agency and similar authorities determine coverage and practical use of the vaccines.

You cannot discuss vaccination without mentioning the H1N1-virus-mediated swine influenza breakout in 2009. “It was very unfortunate” Karin says. “There was a mass vaccination in Sweden but the influenza epidemic did not end up as seriously as predicted, and about 150 individuals developed narcolepsy as an unwanted side-effect. These young individuals developed antibodies against the hypocretin receptor, a protein which regulates sleep in the brain and is physically shaped very similar to the virus protein”.

Good can always get better
The mapping done by Karin’s group generates knowledge about the initial immune mechanisms of vaccination. If you know the chain of events in detail the vaccine can be more optimally designed, for example by developing better adjuvants, the molecules helping to stimulate the body’s immune response. Those vaccines that contain live attenuated or killed whole viruses are easily recognizable for the innate immune system that responds with an immune response similar to that following a real virus infection. While these vaccines are very potent this strategy is not feasible for serious infections such as HIV. That is why it is currently more common to work with recombinant vaccines for which specific antigens or antigen particles are artificially manufactured. However, these vaccines are not as potent as the natural ones and therefore need adjuvants to boost the immune system in order to create a protection that is sufficiently strong.

Illustration: Liz Thompson

Karin explains that more recently developed vaccines such as those for HPV and Hepatitis B are comprised of recombinant virus-like particles reminiscent of spheres whereby the antigens are ‘spiked’ around the surface, making it easy for the immune cells to interact and induce stronger responses. The spiky structure also make it easier for the particles to stick for a longer time in the lymph nodes, giving the immune cells a larger window of interaction with the antigens exposed.

Another potential development of vaccine efficacy regards their distribution in the body. The research group investigates whether it is possible to inject the vaccine in the skin instead of the muscle. In the dermal layers of the skin the number of immune cells, especially dendritic cells, is higher than in the muscle. The skin is the organ in charge of defending the body against the surrounding environment so applying the vaccine in the skin should give a better immune response. Vaccination would also become less expensive as smaller doses of the vaccine could be used. It is more difficult technically to inject the vaccine in the skin and the risk of having a skin reaction is increased. “The frustration that comes with the job is that it is not the intellect putting boundaries on what we can do as the immune system is capable of doing so many things, but there are restrictions of what we can and cannot test. If you have results leading to clinical trials there is not always the possibility to go back after 15-20 years of studies to investigate additional mechanisms,” Karin says. But the work towards an approved vaccine is a strong motivator. Karin sums it up: “I get to work with something that makes a difference for many people, and that gives me a good feeling.”

Text: Ingela Loell
Photo: Ulf Sirborn, KI
Illustration: Liz Thompson

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