title: Mucosal vaccine delivery of antigens tightly bound to an adjuvant particle made from food-grade bacteria.
abstract: Mucosal immunization with subunit vaccines requires new types of antigen delivery vehicles and adjuvants for optimal immune responses. We have developed a non-living and non-genetically modified gram-positive bacterial delivery particle (GEM) that has built-in adjuvant activity and a high loading capacity for externally added heterologous antigens that are fused to a high affinity binding domain. This binding domain, the protein anchor (PA), is derived from the Lactococcus lactis AcmA cell-wall hydrolase, and contains three repeats of a LysM-type cell-wall binding motif. Antigens are produced as antigen-PA fusions by recombinant expression systems that secrete the hybrid proteins into the culture growth medium. GEM particles are then used as affinity beads to isolate the antigen-PA fusions from the complex growth media in a one step procedure after removal of the recombinant producer cells. This procedure is also highly suitable for making multivalent vaccines. The resulting vaccines are stable at room temperature, lack recombinant DNA, and mimic pathogens by their bacterial size, surface display of antigens and adjuvant activity of the bacterial components in the GEM particles. The GEM-based vaccines do not require additional adjuvant for eliciting high levels of specific antibodies in mucosal and systemic compartments.
authors.affiliation: BiOMaDe Technology Foundation, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Maarten L
authors.initials: ML
authors.lastname: van Roosmalen
authors.forename: Rolf
authors.initials: R
authors.lastname: Kanninga
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Khattabi
authors.forename: Jolanda
authors.initials: J
authors.lastname: Neef
authors.forename: Sandrine
authors.initials: S
authors.lastname: Audouy
authors.forename: Tjibbe
authors.initials: T
authors.lastname: Bosma
authors.forename: Anneke
authors.initials: A
authors.lastname: Kuipers
authors.forename: Eduard
authors.initials: E
authors.lastname: Post
authors.forename: Anton
authors.initials: A
authors.lastname: Steen
authors.forename: Jan
authors.initials: J
authors.lastname: Kok
authors.forename: Girbe
authors.initials: G
authors.lastname: Buist
authors.forename: Oscar P
authors.initials: OP
authors.lastname: Kuipers
authors.forename: George
authors.initials: G
authors.lastname: Robillard
authors.forename: Kees
authors.initials: K
authors.lastname: Leenhouts
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods*; D015870:Gene Expression / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006358:Hot Temperature; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D013294:Lactococcus lactis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology; D051379:Mice; D009113:Muramidase / Q000235:genetics; D009666:Nose / Q000276:immunology; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology; D014170:Transformation, Genetic; D014238:Trichloroacetic Acid / Q000737:chemistry; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014238:Trichloroacetic Acid; C092497:AcmA protein, Lactococcus lactis; D009113:Muramidase