Adenoviral vectors infect B lymphocytes in vivo

Abstract

B cells are the antibody-producing arm of the adaptive immune system and play a critical role in controlling pathogens. Several groups have now demonstrated the feasibility of using engineered B cells as a therapy, including infectious disease control and gene therapy of serum deficiencies. These studies have largely utilized exvivo modification of the cells. Direct invivo engineering would be of utility to the field, particularly in infectious disease control where the infrastructure needs of exvivo cell modification would make a broad vaccination campaign highly challenging. In this study we demonstrate that engineered adenoviral vectors are capable of efficiently transducing murine and human primary B cells both exvivo and invivo. We found that unmodified human adenovirus C5 was capable of infecting B cells invivo, likely due to interactions between the virus penton base protein and integrins. We further describe vector modification with B cell-specific gene promoters and successfully restrict transgene expression to B cells, resulting in a strong reduction in gene expression from the liver, the main site of human adenovirus C5 infection invivo.