The present invention provides a recombinant adenovirus vector characterized by the partial or total deletion of adenoviral E2B function and having an expression cassette containing a heterologous sequence encoding a protein of interest inserted into the E1 region. Such vectors are designed to reduce or eliminate the occurrence of replication competent adenovirus contamination. Additionally, the expression cassette of the vector may contain one or more regulatory elements capable of increasing the expression of the heterologous sequence and/or reducing the expression of viral proteins. Such a reduction in expression of viral proteins reduces the cytotoxicty and immunogenicity of the adenovirus vectors when administered in vivo. Transformed production host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention.