Possible monitoring of vaccine effectiveness with MHC tetramers: Influenza model

Evaluation of specific antiviral immunity in either influenza infected or immunized humans has been considered as the only reliable indicator of protective immunity and virus resistance. Antiviral immunity has usually been assessed by antiviral antibody determination in paired sera (seroconversion). This method evaluates only the capacity of B cells to secrete antiviral antibodies, while T-cells as the most important cells in antiviral immune reactions are not directly analyzed. We plan to use new MHC Tetramer technology for the ex vivo quantitation of influenza-specific T cells. Enumeration of CD8+ influenza specific T-cells requires cognate recognition of the T cell receptor by a Class I MHC. This will be achieved using custom designed HLA-A 0201-restricted influenza matrix protein (FLU) tetramer. Once T cells expressing specific receptors have being stained using these tetramers, their function can be assessed by costaining with antibodies to cytokines, chemokines or perforin. The aim of this project is to investigate whether this method could serve as a routine, possibly World Health Organization recommended method, for testing the efficacy of currently used and novel vaccines.