iMed Challenge

Molecular basis and early predictors of non-responsiveness to hepatitis B vaccination

Vaccination represents the most cost-efficient strategy to prevent life threatening diseases caused by infectious pathogens, and its therapeutic use for both communicable and non-communicable diseases is also gaining considerable interest.

However, vaccine efficacy can strongly vary amongst vaccinees. Several host factors (e.g. age, immune status, genetic background) and vaccine characteristics itself such as antigen structure, adjuvantation, and mode of delivery can influence the response to a vaccine. Thus, long-lasting protective immunity is not always achieved, which in most – if not all – cases depends on the induction of protective antibodies.

Early prediction of responsiveness to vaccines

Therefore, an in-depth understanding of the underlying immunological and molecular mechanisms in vaccine responders and non-responders is essential for early prediction of responsiveness to vaccines in terms of efficacy and safety, to improve vaccination coverage and to advance the development of individualized vaccination strategies. 

In the iMed program, the HZI together with Twincore and the Medical School in Hanover, and the HMGU together with the two university hospitals in Munich have already initiated research studies aimed at elucidating the mechanisms of responders and non-responders to an adjuvanted subunit influenza vaccine in the elderly and to a live attenuated yellow fever vaccine, respectively. 

Investigating the variability of hepatitis B vaccine responses

Those already ongoing vaccination studies will be complemented in a new project by investigating the variability of hepatitis B vaccine responses. WHO in 2015 recommended the world-wide implementation of hepatitis B vaccines in infants after birth and non-vaccinated children and adults to reduce the disease burden. However, approximately 10% of hepatitis B vaccinated individuals do not adequately respond. So far, the mechanism leading to non-responsiveness and the underlying functional deficits remain elusive.

The major strategic goals of this project are:

  1. to investigate the underlying immunological and molecular mechanisms, and genetic determinants of responsiveness to hepatitis B vaccination in responders and non-responders, 
  2. to study the responsiveness of hepatitis B vaccine responders and non-responders to an unrelated influenza vaccine, 
  3. to identify early predictive biomarkers for vaccine efficacy, and 
  4. to evolve new strategies to overcome non-responsiveness to hepatitis B vaccination. 

The latter will be done in an approved clinical trial, using a third generation hepatitis B vaccine (SciBVac®) that will be tested for its capacity to overcome hepatitis vaccine non-responsiveness. 

Multi-scale Data

The multi-scale data obtained from these cohorts will be analyzed by the iMed multicenter systems medicine platforms and by thorough immune monitoring to identify early predictors of responsiveness to vaccines.

Mathematical models and training algorithms will be instrumental to determine molecular signatures for prediction of vaccination efficacy.

Highly interdisciplinary project 

This highly interdisciplinary project encompassing immunology, molecular biology and computer-based approaches expects to give new insights into the mechanisms of vaccine non-responsiveness, to expand the identification of immunological and molecular signatures in responders and non-responders, as well as to determine biomarkers for successful vaccination - until now a main unsolved challenge in vaccinology. It will in addition drive forward the development of highly effective personalized vaccination strategies.

Investigators:  

  • HZI: Carlos A. Guzman, Ulrich Kalinke, Esteban Vargas, Frank Pessler, Christine Falk
  • HMGU: Ulrike Protzer, Tanja Bauer, Hedwig Roggendorf, Percy Knolle
  • DKFZ: Christof von Kalle, Manfred Schmidt
  • DZNE: Stefan Bonn

Beteiligte Gruppen