ANTIBODY TO CD40 LIGAND INHIBITS BOTH HUMORAL AND CELLULAR IMMUNE-RESPONSES TO ADENOVIRAL VECTORS AND FACILITATES REPEATED ADMINISTRATION TO MOUSE AIRWAY

Adenoviral vectors have been used successfully to transfer the human C FTR cDNA to respiratory epithelium in animal models and to CF patients in vivo. However, studies done primarily in mice, indicate that prese nt vector systems have limitations. Among other things, transgene expr ession in the lung is transient and the production of neutralizing ant ibodies against adenovirus correlates with a reduced ability to readmi nister a vector of the same serotype. Here we demonstrate that in mice , a transient blockade of costimulation between activated T cells and B cells/antigen presenting cells using a monoclonal antibody (MR1) aga inst murine CD40 ligand inhibits the development of neutralizing antib odies to adenoviral (Ad) vector. MR1 also decreased the cellular immun e response to Ad vector and allowed an increase in persistence of tran sgene expression. Furthermore, when administered with a second dose of Ad vector to mice preimmunized against vector, MR1 was able to interf ere with the development of a secondary antibody response and allowed for high levels of transgene expression upon a third administration of vector to the airway.