Enhancement of the in vivo antibody response by an 8-derivatized guanine nucleoside.
The capacity of the C8-substituted guanine ribonucleosides to enhance the in vivo humoral immune response to the protein antigen, human gamma globulin (HGG), in A/J mice was evaluated. It has been shown recently that the C8-substituted guanine ribonucleosides are a new class of potent adjuvant for humoral immune responses to the sheep erythrocyte antigen. The current studies extend these findings to HGG with 8-bromoguanosine (8BrGuo), a representative of this group of nucleosides. The adjuvant activity of 8BrGuo in this system is highly dose and time dependent. Although 8BrGuo enhanced responses when injected either early (Day 0) or late (Day 4 or 5) after immunization, its administration on Day 1 or 2 most often led to no enhancement, suggesting that 8BrGuo may act on two events separated by a resistant stage in an ongoing immune response. The plaque-forming cell (PFC) response to HGG was enhanced optimally at doses as low as 1 mg 8BrGuo/mouse administered either on the day of immunization or 4 days thereafter. In contrast, however, serum anti-HGG antibody concentration assayed by enzyme-linked immunosorbent assay (ELISA) was enhanced only at doses of 10 mg or more, injected on the day of immunization, but doses as low as 1 mg were effective on Day 4. 8BrGuo was also an effective adjuvant when injected after antigen administration in incomplete Freund's adjuvant or when administered by several different routes (intraperitoneal, subcutaneous, oral).
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000921:Antibody-Producing Cells / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006151:Guanosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006462:Hemolytic Plaque Technique; D006801:Humans; D007136:Immunoglobulins / Q000008:administration & dosage / Q000276:immunology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D013997:Time Factors
D000276:Adjuvants, Immunologic; D007136:Immunoglobulins; D006151:Guanosine; C035169:8-bromoguanosine; D005620:Freund's Adjuvant