Identification of individual anti-viral immune signatures and early predictors for successful vaccination strategies
Our understanding of antiviral immune responses is still fragmentary and based to a great extent on experimental studies with inbred mouse lines. We have very limited understanding of the underlying mechanisms for differential individual responses to the same viral agents, vaccines and antiviral therapies in humans. The proposed project aims to provide new insights into these clinically highly relevant unsolved problems by initiating prospective observational cohort studies to dissect immune responses to two anti-viral vaccines:the live-attenuated yellow fever vaccine representing a viral infection and a true “priming” (the vaccinees have never been exposed to the antigens), and the seasonal inactivated influenza vaccine as an example of “boosting” (the vaccinees have been exposed to the antigens and/or related antigens before). The second system will also specifically address the aspect of age-dependence in responses to vaccination in terms of both safety and efficacy, which represents a main unsolved challenge in vaccinology.
The long-term goal of the intended cohorts is to generate large data sets containing detailed information about (i) the innate and adaptive immune responses of different individuals to the same acute viral infection/vaccination, including identification of vaccine-specific T cell receptors at the single nucleotide level, and (ii) their genetic and epigenetic make-up, including SNPs and other variances in genes governing the immune response, and (iii) biomarkers associated with a positive outcome of vaccination. These datasets will enable us to correlate genetic variances at specific loci with the measured immune parameters and will help us to understand inter-individual differences in anti-vaccine responses.
The detailed longitudinal characterization of immune responses in vaccinees covering both innate immunity (including NK cell responses) and adaptive immunity will allow answering questions concerning the predictive value of early parameters/signatures on vaccination success, reactogenicity, and safety. Furthermore, the influenza immunization cohort will focus on comparative analyses in individuals 65 years of age, providing new insights into individual determinants of vaccination success or failure among the elderly.
The outcome of this project is expected to help us to design subject-tailored vaccination strategies to stimulate optimal immune responses, limit the cost associated with vaccination of non-responders and reduce the clinical development costs of candidate vaccines by selecting those individuals for efficacy trials who will maximally benefit from the intervention.
HZI/TWINCORE: Carlos Alberto Guzman, Frank Pessler, Ulrich Kalinke
HMGU/LMU: Simon Rothenfußer, Stefan Endres, Peter Lichter, Ulrike Protzer
DKFZ: Manfred Schmidt, Christof von Kalle
- Vaccinology - Prof. Dr. Carlos A. Guzmán