title: An adenovirus vectored mucosal adjuvant augments protection of mice immunized intranasally with an adenovirus-vectored foot-and-mouth disease virus subunit vaccine.
abstract: Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen that causes severe morbidity and economic losses to the livestock industry in many countries. The oral and respiratory mucosae are the main ports of entry of FMDV, so the stimulation of local immunity in these tissues may help prevent initial infection and viral spread. E. coli heat-labile enterotoxin (LT) has been described as one of the few molecules that have adjuvant activity at mucosal surfaces. The objective of this study was to evaluate the efficacy of replication-defective adenovirus 5 (Ad5) vectors encoding either of two LT-based mucosal adjuvants, LTB or LTR72. These vectored adjuvants were delivered intranasally to mice concurrent with an Ad5-FMDV vaccine (Ad5-A24) to assess their ability to augment mucosal and systemic humoral immune responses to Ad5-A24 and protection against FMDV. Mice receiving Ad5-A24 plus Ad5-LTR72 had higher levels of mucosal and systemic neutralizing antibodies than those receiving Ad5-A24 alone or Ad5-A24 plus Ad5-LTB. The vaccine plus Ad5-LTR72 group also demonstrated 100% survival after intradermal challenge with a lethal dose of homologous FMDV serotype A24. These results suggest that Ad5-LTR72 could be used as an important tool to enhance mucosal and systemic immunity against FMDV and potentially other pathogens with a common route of entry.
authors.affiliation: Department of Animal Science, University of Connecticut, Storrs, CT 06269, United States.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Alejo
authors.forename: Mauro P
authors.initials: MP
authors.lastname: Moraes
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Liao
authors.forename: Camila C
authors.initials: CC
authors.lastname: Dias
authors.forename: Edan R
authors.initials: ER
authors.lastname: Tulman
authors.forename: Fayna
authors.initials: F
authors.lastname: Diaz-San Segundo
authors.forename: Debra
authors.initials: D
authors.lastname: Rood
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Grubman
authors.forename: Lawrence K
authors.initials: LK
authors.lastname: Silbart
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology; D002460:Cell Line; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology; D004926:Escherichia coli / Q000737:chemistry; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D005536:Foot-and-Mouth Disease / Q000276:immunology / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D005822:Genetic Vectors; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D013552:Swine; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D022223:Vaccines, Subunit; D014765:Viral Vaccines; C027538:heat-labile enterotoxin, E coli