title: PLGA-microencapsulation protects Salmonella typhi outer membrane proteins from acidic degradation and increases their mucosal immunogenicity.
abstract: Salmonella (S.) enterica infections are an important global health problem with more than 20 million individuals suffering from enteric fever annually and more than 200,000 lethal cases per year. Although enteric fever can be treated appropriately with antibiotics, an increasing number of antibiotic resistant Salmonella strains is detected. While two vaccines against typhoid fever are currently on the market, their availability in subtropical endemic areas is limited because these products need to be kept in uninterrupted cold chains. Hence, the development of a thermally stable vaccine that induces mucosal immune responses would greatly improve human health in endemic areas. Here, we have combined the high structural stability of Salmonella typhi outer membrane proteins (porins) with their microencapsulation into poly(lactic-co-glycolic acid) (PLGA) to generate an orally applicable vaccine. Encapsulated porins were protected from acidic degradation and exhibited enhanced immunogenicity following oral administration. In particular, the vaccine elicited strong S. typhi-specific B cell responses in Peyer's patches and mesenteric lymph nodes. In sum, PLGA microencapsulation substantially improved the efficacy of oral vaccination against S. typhi.
authors.affiliation: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Carreño
authors.affiliation: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Perez-Shibayama
authors.affiliation: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil-Cruz
authors.affiliation: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Printz
authors.affiliation: Facultad de Quimica, Universidad Nacional Autonoma de Mexico, Mexico D.F., Mexico.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Pastelin
authors.affiliation: Medical Research Unit on Immunochemistry (UIMIQ), Specialties Hospital, National Medical Centre "Siglo XXI", Mexican Social Security Institute (IMSS), Mexico City, Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Isibasi
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland.
authors.forename: Dominic
authors.initials: D
authors.lastname: Chariatte
authors.affiliation: Takeda Pharmaceutical Company, CMC Center, Osaka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tanoue
authors.affiliation: Medical Research Unit on Immunochemistry (UIMIQ), Specialties Hospital, National Medical Centre "Siglo XXI", Mexican Social Security Institute (IMSS), Mexico City, Mexico. Electronic address: constantino@sminmunologia.org.
authors.forename: Constantino
authors.initials: C
authors.lastname: Lopez-Macias
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Gander
authors.affiliation: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland. Electronic address: burkhard.ludewig@kssg.ch.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D019344:Lactic Acid / Q000737:chemistry*; D008198:Lymph Nodes / Q000276:immunology; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D055550:Protein Stability; D012485:Salmonella typhi; D014436:Typhoid-Paratyphoid Vaccines / Q000737:chemistry / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D014436:Typhoid-Paratyphoid Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Antibodies; PLGA microparticles; Salmonella