IMMUNOGENICITY IN MICE OF TANDEM REPEATS OF AN EPITOPE FROM HERPES-SIMPLEX GD PROTEIN WHEN EXPRESSED BY RECOMBINANT ADENOVIRUS VECTORS

The antigenic and immunogenic potential was examined of human adenovir us type 5 (Ad) recombinants carrying and expressing from one to four t andem repeats of a linear neutralizing epitope from the gD protein of herpes simplex virus type 1 (HSV-1) as a fusion with the beta-galactos idase protein. The fusion proteins produced by these Ad vectors in inf ected cell culture reacted with a herpes simplex virus (HSV) epitope-s pecific monoclonal antibody to a degree dependent on the number of epi tope repeats in the protein. Mice immunized by intraperitoneal injecti on of the Ad vectors developed an anti-HSV immune response as measured by ELISA and by HSV-1 neutralization assays. The mean antibody titre induced by a single injection of the Ad vector increased with the numb er of epitope repeats expressed by the recombinant. Any animal that ha d developed a serum-neutralizing titre of at least 1:80 survived chall enge with a normally lethal dose of HSV-2 administered by the intraper itoneal route. Recombinant vectors expressing four repeats of the HSV epitope were as effective in antibody induction and protection as an a denovirus vector carrying and expressing the entire HS V gD protein. T hese results suggest that the expression of tandem repeats of appropri ate epitopic sequences by adenovirus vectors may provide a safe and ef fective, method of immunizing against HS V infection.