IMMUNOMODULATORY EFFECTS OF HSV2 GLYCOPROTEIN-D IN HSV1 INFECTED MICE- IMPLICATIONS FOR IMMUNOTHERAPY OF RECURRENT HSV INFECTION

Immunological analyses in this laboratory and others have suggested th at a nonrecurrent HSV seropositive immune status is more closely corre lated with a type 1 T helper cell (Th1) response characterized by elev ated levels of interferon-gamma and IL2 rather than high titers of vir us-specific antibodies. Effective intervention,vith an immunotherapeut ic vaccine may require modulation of the regulatory network of T helpe r cells such that there is selective restimulation and expansion of th e Th1 response. We have established a murine model for assessing the i mmunomodulatory capacity of an HSV glycoprotein submit vaccine in anim als with pre-existing herpes immunity. Animals were infected with vary ing doses of HSV1 and then administered glycoprotein D (gD) vaccine ad juvanted with aluminum phosphate at 3-week intervals. Observed changes in serological and cellular responses indicated that administration o f subunit vaccine adjuvanted with aluminum phosphate could shift a dom inant Th1 response, induced by sensitization with live HSV, towards a Th2 profile of activity. These data suggest that use of aluminum based adjuvants will not selectively stimulate Th1-associated responses and alternative adjuvants may be required for effective use of subunit va ccine in an immunotherapeutic indication in humans.