Co-immunization of mice with a retroviral DNA vaccine and GITRL-encoding plasmid augments vaccine-induced protection against retrovirus infection.

After more than 30 years of research a HIV vaccine is still not at hand. DNA vectors expressing viral antigens are very safe vaccines, but so far they have not been efficient enough to induced broad protective immunity against retroviruses. One strategy to enhance the efficiency of DNA vaccines is to augment effector T-cell priming against viral components by manipulating regulatory T-cell functions (Treg). Glucocorticoid-induced tumor necrosis factor receptor (GITR) is a molecule that is constitutively expressed on CD4(+) Treg cells, and antibodies or natural ligands binding this molecule can impair Treg cell suppression. Here we demonstrate using the retroviral Friend virus (FV) mouse model, that co-immunization of FV antigens along with GITR-ligand (GITRL) encoding plasmids protected mice efficiently against a FV challenge. On the other hand, treatment of DNA-vaccinated mice with alpha-GITR antibody did not improve vaccine-induced protection at all. Thus, for an effective priming of immunity against FV, GITRL and viral antigens might have to be expressed within the same local environment. The data suggest that limitations in DNA vaccination can be overcome by co-expressing co-stimulatory molecules that potentially manipulate the function of Treg cells during priming of anti-retroviral immunity.