Effectiveness of the quillaja saponin semi-synthetic analog GPI-0100 in potentiating mucosal and systemic responses to recombinant HagB from Porphyromonas gingivalis.
The gram-negative, anaerobic bacterium Porphyromonas gingivalis, has been implicated in the etiology of adult periodontal disease. Among the potential virulence factors of this bacterium, the non-fimbrial adhesin hemagglutinin B (HagB) appears to be involved in the initial adherence of the bacteria to host tissue and the induction of anti-HagB antibody responses affords some protection from experimental alveolar bone loss. In the present study, we have investigated the ability of the quillaja saponin derivative GPI-0100 to act as an immunostimulant of responses to HagB following subcutaneous (s.c.) or intranasal (i.n.) immunization of mice. We have also compared the immunopotentiating ability of GPI-0100 with that of five other adjuvants. Evidence is provided that GPI-0100 was more effective than monophosphoryl lipid A and alum in inducing serum anti-HagB responses following s.c. immunization. A comparison of the responses induced following i.n. immunization with HagB and adjuvant revealed that the heat-labile toxin of Escherichia coli (LT) and the non-enzymatic mutant LT (E112K), followed by GPI-0100 potentiated higher serum and mucosal anti-HagB antibody responses, which in most cases were higher than those seen with the other adjuvants tested (i.e. monophosphoryl lipid A, alum and the B subunit of cholera toxin). Furthermore, a difference was seen in the nature of the serum IgG anti-HagB response based on the adjuvant used and route of immunization. These results demonstrate the effectiveness of GPI-0100 as both a systemic and mucosal adjuvant and support its potential use in the development of vaccines against periodontal, as well as other pathogens.
D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002772:Cholera Toxin / Q000494:pharmacology; D005260:Female; D006388:Hemagglutinins / Q000276:immunology*; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D037102:Lectins; D008050:Lipid A / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology; D010710:Phosphates / Q000494:pharmacology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D031990:Quillaja / Q000737:chemistry*; D011994:Recombinant Proteins / Q000276:immunology; D012463:Saliva / Q000276:immunology; D012503:Saponins / Q000494:pharmacology; D014621:Vagina / Q000276:immunology
D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C484998:GPI0100; C098582:HagB protein, Porphyromonas gingivalis; D006388:Hemagglutinins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D037102:Lectins; D008050:Lipid A; D010710:Phosphates; D011994:Recombinant Proteins; D012503:Saponins; D002772:Cholera Toxin; C012714:aluminum phosphate