THE GH-GL COMPLEX OF HERPES-SIMPLEX VIRUS (HSV) STIMULATES NEUTRALIZING ANTIBODY AND PROTECTS MICE AGAINST HSV TYPE-1 CHALLENGE

The herpes simplex virus type 1 (HSV-1) gH-gL complex which is found i n the virion envelope is essential for virus infectivity and is a majo r antigen for the host immune system. However, little is known about t he precise role of gH-gL in virus entry, and attempts to demonstrate t he immunologic or vaccine efficacy of gH and gL separately or as the g H-gL complex have not succeeded. We constructed a recombinant mammalia n cell line (HL-7) which secretes a soluble gH-gL complex, consisting of gH truncated at amino acid 792 (gHt) and full-length gL. Purified g Ht-gL reacted with gH- and gL-specific monoclonal antibodies, includin g LP11, which indicates that it retains its proper antigenic structure . Soluble forms of gD (gDt) block HSV infection by interacting,vith sp ecific cellular receptors. Unlike soluble go, gHt-gL did not block HSV -1 entry into cells, nor did it enhance the blocking capacity of go. H owever, polyclonal antibodies to the complex did block entry even when added after virus attachment. In addition, these antibodies exhibited high titers of complement-independent neutralizing activity against H SV-1. These sera also cross-neutralized HSV-2, albeit at low titers, a nd cross-reacted with gH-2 present in extracts of HSV-2-infected cells . To test the potential for gHt-gL to function as a vaccine, BALB/c mi ce were immunized with the complex. As controls, other mice were immun ized with go purified from HSV-infected cells or were sham immunized. Sera from the gD- or gDt-gl-immunized mice exhibited high titers of vi rus neutralizing activity. Using a zosteriform model of infection, we challenged mice with HSV-1. All animals showed some evidence of infect ion at the site of virus challenge. Mice immunized with either go or g Ht-gL showed reduced primary lesions and exhibited no secondary zoster iform lesions. The sham-immunized control animals exhibited extensive secondary lesions. Furthermore, mice immunized with either go or gHt-g L survived virus challenge, while many control animals died. These res ults suggest that gHt-gL is biologically active and may be a candidate for use as a subunit vaccine.