TUNING THE EFFICACY OF INFLUENZA A VIRUS NUCLEOPROTEIN-BASED T-CELL VACCINES WITH CELL DEATH-MODULATING EFFECTORS

SCHOTSAERT M.; IBAÑEZ L.I.; VANDENABEELE P.; FIERS W.; SAELENS X.

Brujas, Bélgica

Congreso; 14th International Negative Strand Virus Meeting 2010; 2010

Influenza is a vaccine-preventable respiratory disease with high social and economical impact. The current vaccines target the hypervariable membrane proteins hemagglutinin and neuraminidase, necessitating yearly updates of the vaccines. Vaccines based on the internal, more conserved, proteins such as the nucleoprotein (NP) or the matrix protein can induce a heterosubtypic immune response in mice resulting in protection against different strains of influenza viruses. The protective mechanism is often T-cell based, thereby most probablyrelying on cross-priming and -presentation. It has been shown that induction of cell death can result in more efficient cross-priming events. DNA vaccines are known to be a good means for induction of T-cell responses. By combining NP with the cell death-related molecule RIP-1 or mutants thereof in a single DNA vaccine vector, we investigate the T-cell activation potential of these vaccines, as well as their protective efficacy after lethal challenge with an influenza virus. T-cell activation is investigated by quantification of IFN-gamma-positive T cells (both CD4 and CD8) after restimulation. A flow cytometry-based killing assay is used to determine cytotoxic T-cell activity. The absence of morbidity and mortality as well as clearance of virus from the lung after lethal challenge is taken as a read-out for protection and are used to define correlates of protection.