ADJUVANT ACTIVITY OF BUTYROLACTONE DRUGS

BUTYROLACTONES ARE NOVEL, NONTOXIC, WATER-SOLUBLE, LOW-MOLECULAR-WEIGHT COMPOSITIONS DEVELOPED BY THE THERACEL CORPORATION. THE KETOBUTYROLACTONES, WHICH ARE IMMUNOSTIMULATORY, WERE ASSESSED FOR THEIR UTILITY AS VACCINE ADJUVANTS. THE EXPERIMENTAL DESIGN EMPLOYED IMMUNIZATION WITH COMMERCIALLY PREPARED VACCINES TO TETANUS AND INFLUENZA, AND A SYNTHETIC PEPTIDE OF HIV-1, GP-41. THEVACCINES WERE ADMINISTERED IN EITHER SOLUBLE OR ALUM-ADSORBED FORMS, AND THE EFFECT OF TREATMENT WITH THE BUTYROLACTONES ON HUMORAL AND CELL-MEDIATED IMMUNE RESPONSESWAS ASSESSED. BECAUSE BUTYROLACTONES ARE ACTIVE ORALLY, THE CONCEPT OF AN ORAL ADJUVANT FOLLOWING VACCINATION WAS EVALUATED. A KETOBUTYROLACTONE (BL-009) WAS SELECTED AS A POTENTIAL ADJUVANT BASED ON ITS ABILITY TO STIMULATE BOTH HUMORAL AND CELL-MEDIATED IMMUNITY (CMI). BL-009, WHEN ADMINISTERED ORALLY, STIMULATED ANTIBODY FORMATION IN ANIMALS RECEIVING ALUM-ADSORBED TETANUS TOXOID AND INFLUENZA HEMAGGLUTININ. ORALLY ADMINISTERED BL-009 SHOWED A SIGNIFICANT ENHANCEMENT OF CMI RESPONSES OF MICE TO THE INTRAMUSCULARLY INJECTED, SOLUBLE HIV-1 PEPTIDE. THE HUMORAL RESPONSE TO THE PEPTIDE IN BOTH THE SOLUBLE AND ALUM-ADSORBED FORMS WAS ALSO ENHANCED. THESE RESULTS SUPPORT THE NEED FOR CONTINUED RESEARCH ON THE IMMUNOSTIMULATORY ACTIVITY OF BUTYROLACTONES IN COMBINATION WITH NEW VACCINES WITH EMPHASIS ON THOSE VACCINES UNDER DEVELOPMENT FOR THE PREVENTION OF AIDS.