title: Modulating the adjuvanticity of alum by co-administration of muramyl di-peptide (MDP) or Quil-A.
abstract: The characterization of the immunological cascades of the innate immune system activated by pathogen associated molecular patterns (PAMP) recognized by pattern recognition receptors (PRR) have allowed the elucidation of the mechanisms underlying the immunomodulatory properties of adjuvants. Thus, the combinatorial use of adjuvants with specific, complementary functions is investigated to achieve tailored immune responses to subunit vaccines. We have previously shown how combinatorial administration of chitosan and cholera toxin B or muramyl-di-peptide (MDP) intranasally, but not intramuscularly, can allow small doses of MDP which, when administered alone cannot adjuvantise Helicobacter pylori urease (rUre), achieve an immunomodulatory effect through the specific physiological effect of chitosan. The aim of this study was to investigate if in the context of rUre the adjuvantising effect of MDP could be realized via the intramuscular route by combination with aluminium hydroxide, as compared with the routinely used veterinary adjuvant combination of alum and Quil-A. Serum IgG kinetics were comparable between the two adjuvant combination groups. However, the alum + MDP combination afforded higher antigen-specific recall responses in splenocyte cultures, associated with elevated release of the type I immune response cytokines IFN-gamma and IL-2. This data suggests that the adjuvanticity of MDP can be modulated in the context of alum in a manner dissimilar to that of Quil-A, achieving a balancing effect on the responses elicited by alum adjuvantisation.
authors.affiliation: Centre for Drug Delivery Research, Department of Pharmaceutics, The School of Pharmacy, University of London, London WC1N 1AX, UK.
authors.forename: Sterghios A
authors.initials: SA
authors.lastname: Moschos
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Bramwell
authors.forename: Satyanarayna
authors.initials: S
authors.lastname: Somavarapu
authors.forename: H Oya
authors.initials: HO
authors.lastname: Alpar
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D005260:Female; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D062605:Quillaja Saponins; D012503:Saponins / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D062605:Quillaja Saponins; D012503:Saponins; C041524:aluminum sulfate; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C046386:Quil A; D007371:Interferon-gamma