Summary DNA vectors expressing an antigen derived from a pathogen or a cancerous cell have been shown, after inoculation into experimental animals, to trigger de novo synthesis of foreign proteins, which induce an immune response. This immune response can be modulated by coinoculation of vectors encoding either cytokines or costimulatory molecules. A variety of cytokines such as granulocyte/macrophage colony-stimulating factor (GM-CSF), lL-2, IL-4, IL-12 and IFN-y, as well as the costimulatory molecule B7.I. have been tested to date for their ability to amplify the immune response to genetic vaccines. Although the results obtained thus far clearly show that coadministration of vectors expressing immunomodulatory molecules, such as cytokines, may increase the efficacy of genetic vaccines, this approach is currently considered unsuitable for use in human patients due to the potential side effects of persistent cytokine expression.

An E1-deleted, replication-defective adenovirus recombinant of the human strain 5 expressing the rabies virus glycoprotein, termed Adrab.gp, was tested in young mice. Mice immunized at birth with the Adrab.gp construct developed antibodies to rabies virus and cytokine-secreting lymphocytes and were protected against subsequent challenge. Maternal immunity to rabies virus strongly interferes with vaccination of the offspring with a traditional inactivated rabies virus vaccine. The immune response to the rabies virus glycoprotein, as presented by the Adrab.gp vaccine, on the other hand, was not impaired by maternal immunity. Even neonatal immunization of mice born to rabies virus-immune dams with Adrab.gp construct resulted in a long-lasting protective immune response to rabies virus, suggesting that this type of vaccine could be useful for immunization shortly after birth. Nevertheless, pups born to Adrab.gp virus-immune dams showed an impaired immune response to the rabies virus glycoprotein upon vaccination with the Adrab.gp virus, indicating that maternal immunity to the vaccine carrier affected the offspring's immune response to rabies virus.

No abstract