title: Loss of sialic acid binding domain redirects protein σ1 to enhance M cell-directed vaccination.
abstract: Ovalbumin (OVA) genetically fused to protein sigma 1 (pσ1) results in tolerance to both OVA and pσ1. Pσ1 binds in a multi-step fashion, involving both protein- and carbohydrate-based receptors. To assess the relative pσ1 components responsible for inducing tolerance and the importance of its sialic binding domain (SABD) for immunization, modified OVA-pσ1, termed OVA-pσ1(short), was deleted of its SABD, but with its M cell targeting moiety intact, and was found to be immunostimulatory and enhanced CD4(+) and CD8(+) T cell proliferation. When used to nasally immunize mice given with and without cholera toxin (CT) adjuvant, elevated SIgA and serum IgG responses were induced, and OVA-pσ1(s) was more efficient for immunization than native OVA+CT. The immune antibodies (Abs) were derived from elevated Ab-forming cells in the upper respiratory tissues and submaxillary glands and were supported by mixed Th cell responses. Thus, these studies show that pσ1(s) can be fused to vaccines to effectively elicit improved SIgA responses.
authors.affiliation: Department of Food Chemistry, Institute of Food Research, Polish Academy of Science, Olsztyn, Poland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Zlotkowska
authors.forename: Massimo
authors.initials: M
authors.lastname: Maddaloni
authors.forename: Carol
authors.initials: C
authors.lastname: Riccardi
authors.forename: Nancy
authors.initials: N
authors.lastname: Walters
authors.forename: Kathryn
authors.initials: K
authors.lastname: Holderness
authors.forename: Gayle
authors.initials: G
authors.lastname: Callis
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Rynda-Apple
authors.forename: David W
authors.initials: DW
authors.lastname: Pascual
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002772:Cholera Toxin / Q000276:immunology; D004848:Epithelium / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology*; D010581:Peyer's Patches / Q000166:cytology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000276:immunology; D017384:Sequence Deletion; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D036022:Capsid Proteins; D011993:Recombinant Fusion Proteins; D014612:Vaccines; C031728:sigma 1 protein, reovirus; D010047:Ovalbumin; D002772:Cholera Toxin; D019158:N-Acetylneuraminic Acid