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Title: An adenovirus vectored mucosal adjuvant augments protection of mice immunized intranasally with an adenovirus-vectored foot-and-mouth disease virus subunit vaccine

Author
item ALEJO, DIANA - University Of Connecticut
item MORAES, MAURO - University Of Connecticut
item LIAO, XIAOFEN - University Of Connecticut
item DIAS, CAMILLA - Oak Ridge Institute For Science And Education (ORISE)
item TULMAN, EDAN - University Of Connecticut
item Diaz San Segundo, Fayna
item ROOD, DEBRA - University Of Connecticut
item Grubman, Marvin
item SILBART, LAWRENCE - University Of Connecticut

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2013
Publication Date: 3/13/2013
Citation: Alejo, D.M., Moraes, M.P., Liao, X., Dias, C.C., Tulman, E.R., Diaz San Segundo, F.C., Rood, D., Grubman, M.J., Silbart, L.K. 2013. An adenovirus vectored mucosal adjuvant augments protection of mice immunized intranasally with an adenovirus-vectored foot-and-mouth disease virus subunit vaccine. Vaccine. 313(18):2302-2309.

Interpretive Summary: Foot-and-mouth disease virus (FMDV) is an antigenically variable virus consisting of 7 serotypes and multiple subtypes and causes an economically devastating disease of cloven-hoofed animals. FMDV is a mucosal pathogen that enters the animal via the respiratory route. Vaccines produced by chemical inactivation of virus and a novel subunit vaccine which contains the coding region for the viral structural proteins but does not contain infectious FMDV are available. This subunit vaccine is delivered by a replication-defective human adenovirus (Ad5-FMD). Although both vaccines are effective in protecting animals neither induces mucosal immunity and therefore virus replication occurs at the initial site of FMDV infection. To address this limitation we cloned various mucosal adjuvants into the Ad5 vector. Mice vaccinated with the Ad5-FMD vaccine and the Ad5-adjuvant vector survived challenge with a lethal dose of FMDV and did not develop viremia, while mice given only the Ad5-FMD vaccine did not survive. These results suggest that induction of mucosal immunity may enhance the protective effect of an FMD vaccine by blocking virus replication at the initial site of infection.

Technical 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 has 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 and 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. This 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 entry pathway.