Genetically engineered poxviruses: a novel approach to the construction of live vaccines

Abstract

Gene splicing techniques have been used to modify the smallpox vaccine virus thus providing a generic approach for the construction of live vaccines directed against a variety of heterologous infectious disease agents. The technique involves translocating a particular gene from an infectious agent into the genetic material of the smallpox vaccine virus. This unique foreign gene, selected because it contains the information essential for the synthesis of an antigen important in immunity to that particular infectious disease agent, is now expressed under the regulation of the engineered smallpox vaccine virus. On immunization with this live recombinant vaccine, the body is fooled into thinking that it was infected by the foreign infectious disease agent and mounts a defensive attack resulting in immunity to that particular infectious agent. Three examples of this approach are provided. Thus, smallpox vaccine viruses were engineered to express genes encoding the hepatitis B virus surface antigen (HBsAg), the herpes simplex virus glycoprotein D (HSV-gD) and the haemagglutinin (HA) from influenza virus. These foreign gene products when synthesized in vitro under vaccinia virus regulation were shown to be antigenic by a variety of serological tests. When these recombinant vaccinia viruses were inoculated into laboratory animals, the heterologous gene products elicited the production of specific antibodies thus demonstrating that they were immunogenic. Serum neutralizing antibodies were demonstrated to be present for both influenza and herpes simplex viruses. Additional studies in mice showed that a recombinant smallpox vaccine virus expressing a gene from herpes simplex virus effectively protected the mice when subsequently challenged with what would normally be lethal doses of infectious herpes simplex virus.