Lipid Leaders: Dennis Christensen

In this Lipid Leaders interview, we get insight from Croda Pharma's own Global Head of R&D - Adjuvant Systems, Dennis Christensen, PhD. Keep reading to learn more about adjuvants and the role they play in vaccines, as well as where the technology may be heading.

Tell us a little bit about yourself 
My name is Dennis Christensen, and I recently started in Croda as Head of Global Research & Development for Adjuvant Systems, after having worked for 18 years as a vaccine researcher in a public research organization in Denmark. I am Cand Pharm of education with a Phd in vaccine formulation. I live in Frederiksberg in Copenhagen with my wife and two kids, a 14 year old boy and a 12 year old girl.

Did you always want to be a scientist? Who most influenced you to go down this path?                                     
I always liked the natural sciences the best in school and also chose the science line in highschool. I was the first in my family to go to university though and I think it was not until highschool that this path was on my mind.  It was my chemistry teacher that told me that I should choose something with medicine, and specifically suggested that I should choose pharmacy. At the university, I liked the lab lectures the best, and I guess I always wanted to stir the pot and have never really been fond of routine tasks, so research was a quite natural choice for me.

What do you consider to be the greatest breakthrough in vaccine technology in the last decade?
There have been many breakthroughs on a scientific level over the last 10 years, all building on major discoveries in immunology stretching back to the 1990’s. But, we have also learned that breakthroughs are only true breakthroughs when they have shown their worth in humans. Many would probably say that the success of the mRNA technology is the biggest breakthrough, but I must say that I am more impressed about the success of the HPV and Shingles vaccines, based on adjuvanted virus-like particles (VLPs) and recombinant proteins respectively.

Could you please explain the role that adjuvants have in vaccines, how they work?
From a pharmaceutical point of view, vaccination is about;

1) presenting sufficient amounts of the right antigen

2) in the right conformation,

3) to the right cell populations,

4) while supporting with the right co-stimuli

5) for a sufficient amount of time.

And basically, the adjuvants play a major role in four out of the five points. In modern vaccine technologies, those components that typically alarmed the immune system has been removed. This relates to the particular size of the pathogens that facilitate uptake into immune cells as well as specific pathogen associated molecular patterns that activate the immune system to react in a certain way through downstream activation to produce a certain immune fingerprint. It is these mediators of immune activation that the adjuvant shall replace and it therefore often comprises both a delivery system and an immunostimulatory component.

Why is it sometimes necessary to use a combination of adjuvants to elicit a potent immunogenic response?
As mentioned above, the immune system needs both proper presentation of the vaccine and immunostimulation to induce the right type of immunity, which is why modern adjuvants typically consist of a delivery system and an immunostimulatory. In recent years, it has also become evident that a combination of different immunostimulators can result in a synergistic effect that can increase potency without also increasing the side effects. Furthermore, a combination of immunostimulators are often necessary to obtain the most optimal immune fingerprint.

What are some of the recent advances in vaccine adjuvants technologies that might allow more potent antigen specific responses?
I am not sure if the potency is the most interesting when it comes to modern adjuvant technologies. Potency might be important, but only if it matches with the right correlate of protection. I rather appreciate the ability to steer the immunity to certain immune fingerprints. This example includes the ability to induce different flavors of T-cell immunity such as Th1-, Th2- or Th17 bias through combination of different immunostimulators and delivery systems.

What potential advantages do cationic adjuvant formulations offer compared to other traditional adjuvants?
First of all, the cationic adjuvant formulations ensure a strong co-localisation between the antigen and the adjuvant, which is of crucial importance for induction of especially T-cell immunity. But it also ensures a prolonged presentation of the vaccine to the immune system, thus improving memory profile of the inducted immunity. Finally, the initial activation of the immune system is very localized to the site of injection. This reduces the systemic side effects often observed with vaccines, resulting in fever and systemic pain.

If you had to give one piece of advice to someone in the research field, what would you tell them? 
Working with vaccines and vaccine adjuvants is really a cross-sectional exercise including fields like immunology, drug-delivery, pharmacology, pharmaceutical formulation and chemistry so make sure that you and your research team can comprehend all these fields!