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 that a nonrecurrent HSV seropositive immune status is more closely correlated with a type 1 T helper cell (Th1) response characterized by elevated levels of interferon-gamma and IL2 rather than high titers of virus-specific antibodies. Effective intervention with an immunotherapeutic vaccine may require modulation of the regulatory network of T helper cells such that there is selective restimulation and expansion of the Th1 response. We have established a murine model for assessing the immunomodulatory capacity of an HSV glycoprotein subunit vaccine in animals with pre-existing herpes immunity. Animals were infected with varying doses of HSV1 and then administered glycoprotein D (gD) vaccine adjuvanted with aluminum phosphate at 3-week intervals. Observed changes in serological and cellular responses indicated that administration of subunit vaccine adjuvanted with aluminum phosphate could shift a dominant 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 vaccine in an immunotherapeutic indication in humans.
York
L J
LJ
Lederle-Praxis Biologicals, Pearl River, NY 10965, USA.
Giorgio
D P
DP
Mishkin
E M
EM
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000918:Antibody Specificity; D005260:Female; D006561:Herpes Simplex / Q000276:immunology* / Q000628:therapy*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D012008:Recurrence; D014759:Viral Envelope Proteins / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C040570:glycoprotein D-herpes simplex virus type 2