ERC project in Croatia makes strides forward on vaccine development

Published: 5-Feb-2015

Investigating the potential of a weakened version of a common virus as a new vaccine delivery mechanism


A five-year, €1.8m research project funded by the European Research Council (ERC) has made significant progress towards developing potential new ways of delivering vaccines that could offer better protection against pathogens and diseases for which life-long protective immunity cannot currently be generated, according to its leader.

The Stadvinn project, which received an Advanced Grant in 2012, is investigating the potential of a weakened, or attenuated, version of cytomegalovirus (CMV) – a common virus belonging to the herpes family of viruses – as a new delivery mechanism, or vector, for vaccines.

Professor Stipan Jonjic, based at the University of Rijeka medicine faculty in Croatia, who is leading the Stadvinn project, says it aims to engineer the virus so that it can still replicate in its host and induce a strong immune response against specific infections – one that the immune system will remember – despite being weakened enough to render it harmless, or non-pathogenic.

He explained that the research is centred on a receptor called NKG2D expressed by natural killer (NK) cells – part of the body’s innate immune system – and also by CD8 T-cells, another type of white blood cell that is part of acquired immune response. Jonjic said these T-cells can memorise the contact with foreign antigens from an infection, meaning that any subsequent reinfection with the same pathogen is brought under control quickly.

The research is centred on a receptor called NKG2D expressed by natural killer (NK) cells

His research team has been studying mouse cytomegalovirus (MCMV) genes involved in the regulation of cellular ligands for activating the immune receptor NKG2D, and found that when the scientists constructed recombinant MCMV molecules expressing NKG2D ligand Rae-1 in place of its viral inhibitor, the results demonstrated that such a virus induces a very potent cellular immune response from CD8 T cells.

He said the aim of further studies in the project is to define the molecular basis of the NKG2D-independent immune function of Rae-1.

'A successful completion of these studies will confer new insights into engineering the immune response to viral infections, for designing safe and effective T cell-based vaccines and vaccine vectors,' he said.

Jonjic added that his research team is also 'testing whether we need a persistent replicating virus vector, or we can achieve similar protection with a single round replicating virus vector'.

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