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Trkola

Fakultäten » Medizinische Fakultät » Infektionskrankheiten und Spitalhygiene, Klinik für » Prof. Dr. Huldrych Günthard » Trkola

Completed research project

Title / Titel Defining determinants of broadly neutralizing antibody evolution in viral infection to guide vaccine development
PDF Abstract (PDF, 14 KB)
Summary / Zusammenfassung Building on recent discoveries in the HIV antibody field, we will conduct a systematic screen for broadly neutralizing antibody (bNAb) activity elicited during HIV infection using the extensive sample and data collection of the Swiss HIV Cohort Study (SHCS) and the Zurich Primary HIV Infection study (ZPHI). By assessing the neutralization breadth in approx. 5000 closely monitored individuals at different disease stages spanning the HIV infection of the past 25 years, we will have a unique possibility to address many aspects of neutralizing antibody evolution in HIV infection that urgently await clarification. In order to learn why bNAbs are so rarely induced in natural infection and to unravel how to induce them by vaccination, there is an urgent need to identify and characterize more bNAbs, define their ontogeny, study their
evolution over time and ideally, derive alongside information on the co‐evolving viral envelope gene. A main goal of our study is to obtain insights why bNAb induction, in particular those with elite neutralizing activity, is generally rare in HIV infection. An in depth analysis of which viral, host and disease factors allow the emergence of bNAbs as we propose to conduct here is critical to harness these types for antibodies for vaccines. The comprehensive patient data and specimen that are available within the investigated patient cohorts will empower our study to perform extended systematic and longitudinal analyses that go beyond a mere frequency analysis of antibody responses and have the possibility to confirm and to rule out potential viral, host and disease linked cofactors of bNAb induction. In a second line of experiments that are performed in parallel we will investigate the modulators of neutralizing antibody development in LCMV infection to gain further insight into neutralizing antibody development in the setting of a chronic viral infection which is characterized by mutual escape of virus and antibody responses. Most importantly,
this animal model which has served over the past decades as a key model system to unravel mutual dynamics of a persistently infecting fast evolving virus and a potent cellular and humoral immune response, will be invaluable to identify key parameters of antibody‐mediated protection in a preventive or therapeutic setting.
Keywords / Suchbegriffe neutralizing antibodies, HIV, vaccine, escape, humoral immune response
Project leadership and contacts /
Projektleitung und Kontakte
Prof. Alexandra Trkola (Project Leader) trkola.alexandra@virology.uzh.ch
Funding source(s) /
Unterstützt durch
Other Public Sources (e.g. Federal or Cantonal Agencies)
Swiss Vaccine Research Institute, funded by the The State Secretariat for Education, Research and Innovation (SERI)
In collaboration with /
In Zusammenarbeit mit
Prof. A. Oxenius, ETHZ, Zürich
Prof. H. Günthard, USZ/UZH, Zürich
Dr. R. Kouyos, RSZ/UZH, Zürich
Prof. S. Reddy, ETHZ, BSSE, Basel
Prof. J. Fellay, EPFL, Lausanne
PD Dr. R. Regoes, ETHZ, Zürich

Swiss HIV Cohort Study
Zurich Primary HIV Infection Study
Switzerland
Duration of Project / Projektdauer Jan 2015 to Dec 2018