Vaccines: activatable depot to replace multiple injections

Interview with Dr. Adrian Sprenger, University of Freiburg

Besides antibiotics, vaccines may be the most important development in medicine: they protect us from diseases by "introducing" our immune system to pathogens. This way, a small injection saves us from severe and potentially mortal courses of disease.


Photo: Adrian Sprenger

Dr. Adrian Sprenger; © private

But some vaccines have to be administered in several separate doses. The vaccination is ineffective if the patient misses one or more of the appointments. Dr. Adrian Sprenger from the University of Freiburg explains a possible solution to this problem at it could save patients the trouble of several visits to the physician and increase the vaccination rate in the public.

Dr. Sprenger, you are involved with the design of a drug depot that gradually releases vaccines. How does this work exactly?

Adrian Sprenger: Our “activatable drug depot” makes it possible to administer several doses of a drug and to store it in the body while using only one single injection. Patients can subsequently activate the release of the drug from this depot on their own with an orally administered pill.

This is technically actualized through a biocompatible depot matrix that can store an embedded active ingredient. The depot dissolves during contact with the equally biocompatible compound in the pill and releases the active ingredient.

What is so special about this system is that all of the used components have already been in clinical use for other applications for quite some time. We are therefore able to gauge that this is safe for use in human beings.
Photo: Woman with a pill between her teeth

The drug depot of the Freiburg researchers is activated by taking a pill; © Trautmann

What does the pill contain?

Sprenger: Fluorescein. This is a dye used in ophthalmology to make corneal injuries visible. Many studies prove good tolerance of this dye. The drug depot consists of threadlike biocompatible molecules that are held together by natural biological attraction. The fluorescein in the pill blocks this attraction. After taking the pill, it distributes in the body, dissolves the depot under the skin and is eliminated within twelve hours.

To what extent has this system already been tested? Have you actually already used vaccines with it?

Sprenger: We have inoculated mice against the cancer-causing human papillomavirus (HPV) and the hepatitis B virus with the activatable drug depot. The animals received the first dose of the vaccine along with the second (booster) dose packed in the depot in one single dose. After the allotted time, we fed the mice the trigger pill, thereby dissolving the depot in the bodies of the mice and releasing the booster dose.

We compared this process with the standard method where mice first receive the initial dose and then subsequently the booster dose as an injection. The level of immune response, the quality and therapeutic effect are just as good with our method versus the standard method. We also ensured tissue tolerability of our depot.
The goal is to test the depot in a phase 1 clinical trial, but before we can do this, we still need to collect more preclinical data. This is still going to take some time.
Photo: People in the waiting room of a doctor's office

A lot of people miss consecutive appointments with their physician that are necessary for the success of vaccinations. But patients do not only risk their own health but also cause financial damage to public health systems; © Olsen

How do you rate the chances of success for systematic vaccination using this method?

Sprenger: Vaccination with a single dose injection is of course far more comfortable than with several injections. It is also better suited for daily life. The chief cause in developed countries for incomplete vaccinations is the effort patients need to expend to visit the doctor several times to do this. Originally, the drug depot development traces back to this problem.

With HPV for instance, vaccination is not completed in 70 percent of all patients, because they miss one or both booster shots. This renders the immunization ineffective. If you consider that the global volume for HPV vaccination is more than two billion US dollars per year, it is very expensive for healthcare systems when 70 percent of inoculations are not done correctly.

Our method would have an important added benefit for so-called “developing countries“. On the one hand, it is difficult to ensure refrigeration of the drugs in this instance and to coordinate patients for three separate injections on the other. When you administer the vaccine with one single injection, it could significantly alleviate problems in this area. This is such a major problem to where Bill Gates, when asked in an interview with Science Magazine about the most exciting possible developments in the healthcare sector, said: "We often have trouble delivering the vaccines to the patients. If you could set up a depot in the body, you would only need one single injection for vaccination and would not have to inject multiple times."
Foto: Timo Roth; Copyright: B. Frommann

© B. Frommann

The interview was conducted by Timo Roth and translated from German by Elena O'Meara.