Mucosal vaccine delivery of antigens tightly bound to an adjuvant particle made from food-grade bacteria.
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.
van Roosmalen
Maarten L
ML
BiOMaDe Technology Foundation, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
Kanninga
Rolf
R
El Khattabi
Mohamed
M
Neef
Jolanda
J
Audouy
Sandrine
S
Bosma
Tjibbe
T
Kuipers
Anneke
A
Post
Eduard
E
Steen
Anton
A
Kok
Jan
J
Buist
Girbe
G
Kuipers
Oscar P
OP
Robillard
George
G
Leenhouts
Kees
K
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*
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