The effects of type I interferons following vaccination with adenovirus vectors

Recombinant adenovirus (Ad) vectors elicit potent transgene product-specific T and B cell responses. Most pre-clinical and clinical studies have examined the vaccine efficiency of vectors derived from common human Ad serotypes, such as AdHu5. In order to circumvent problems associated with pre-existing immunity to common human Ads, recent studies have utilized vectors derived from Ads that naturally infect species other than humans. A recombinant vector derived from a chimpanzee Ad, termed AdC68, elicits strong transgene product-specific T and B cell responses in mice that are pre-exposed to AdHu5. It has been proposed that AdC68 vectors should be used in the human population; however, it is important to first study these vectors in small animal models to determine if they share similar characteristics to the well-characterized human Ad vectors. One major difference between AdC68 and AdHu5 vectors is in their ability to induce type I interferons (IFNs). Strikingly, dendritic cells (DCs) produce 5-10 fold more type I IFNs following infection with AdC68 vectors compared to AdHu5 vectors. The following studies were designed to determine if the induction of high levels of type I IFNs is beneficial or detrimental following vaccination with Ad vectors. Specifically, type I IFNs effects on transgene product expression, DC maturation, and the generation of transgene product-specific T and B cell responses were studied. Although type I IFNs were found to promote DC maturation following vaccination with Ad vectors, they inhibited transgene product expression which reduced the priming of transgene product-specific T and B cell responses. Therefore, the induction of high levels of type I IFNs are detrimental following vaccination with Ad vectors