title: Systemic and mucosal immune responses following oral adenoviral delivery of influenza vaccine to the human intestine by radio controlled capsule.
abstract: There are several benefits of oral immunization including the ability to elicit mucosal immune responses that may protect against pathogens that invade through a mucosal surface. Our understanding of human immune biology is hampered by the difficulty in isolating mucosal cells from humans, and the fact that animal models may or may not completely mirror human intestinal immunobiology. In this human pharmacodynamic study, a novel adenovirus vector-based platform expressing influenza hemagglutinin was explored. We used radio-controlled capsules to deliver the vaccine to either the jejunum or the ileum. The resulting immune responses induced by immunization at each of the intestinal sites were investigated. Both intestinal sites were capable of inducing mucosal and systemic immune responses to influenza hemagglutinin, but ileum delivery induced higher numbers of antibody secreting cells of IgG and IgA isotypes, increased mucosal homing B cells, and higher number of vaccine responders. Overall, these data provided substantial insights into human mucosal inductive sites, and aided in the design and selection of indications that could be used with this oral vaccine platform.
authors.affiliation: Vaxart, Inc. 385 Oyster Point #9A, South San Francisco, CA 94080.
authors.forename: Leesun
authors.initials: L
authors.lastname: Kim
authors.affiliation: Vaxart, Inc. 385 Oyster Point #9A, South San Francisco, CA 94080.
authors.forename: C Josefina
authors.initials: CJ
authors.lastname: Martinez
authors.affiliation: Vaxart, Inc. 385 Oyster Point #9A, South San Francisco, CA 94080.
authors.forename: Katie A
authors.initials: KA
authors.lastname: Hodgson
authors.affiliation: Vaxart, Inc. 385 Oyster Point #9A, South San Francisco, CA 94080.
authors.forename: George R
authors.initials: GR
authors.lastname: Trager
authors.affiliation: Vaxart, Inc. 385 Oyster Point #9A, South San Francisco, CA 94080.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brandl
authors.affiliation: Scintipharma, 2201 Regency Rd # 403, Lexington, KY 40503.
authors.forename: Erik P
authors.initials: EP
authors.lastname: Sandefer
authors.affiliation: Scintipharma, 2201 Regency Rd # 403, Lexington, KY 40503.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Doll
authors.affiliation: Vaxart, Inc. 385 Oyster Point #9A, South San Francisco, CA 94080.
authors.forename: Dave
authors.initials: D
authors.lastname: Liebowitz
authors.affiliation: Vaxart, Inc. 385 Oyster Point #9A, South San Francisco, CA 94080.
authors.forename: Sean N
authors.initials: SN
authors.lastname: Tucker
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D004285:Dogs; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007251:Influenza, Human / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology; D061985:Madin Darby Canine Kidney Cells; D008875:Middle Aged; D014611:Vaccination; D064166:Vaccine Potency; D059015:Wireless Technology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines