Date of Completion

5-8-2014

Embargo Period

4-27-2024

Keywords

Adenovirus, FMDV, mucosal immunity, E. coli enterotoxin, adjuvants

Major Advisor

Lawrence Silbart

Co-Major Advisor

Marvin Grubman

Associate Advisor

Antonio Garmendia

Associate Advisor

Paulo Verardi

Associate Advisor

Mauro Moraes

Field of Study

Animal Science

Degree

Doctor of Philosophy

Open Access

Campus Access

Abstract

Foot-and-mouth disease (FMD) is a highly contagious disease that affects domestic and wild cloven-hoofed animals causing very high morbidity that affect animal productivity and trade. Pigs are more susceptible to foot-and-mouth disease virus (FMDV) via the gastrointestinal route, highlighting the importance of mucosal immunity to avoid initial infection, virus replication and spread.

Systemic vaccines are in general poor inducers of mucosal immunity. A subunit vaccine that has the entire FMDV capsid polyprotein-coding region, delivered by replication-defective human adenovirus serotype 5 (Ad5-A24) has proven to be very effective against FMDV when inoculated intramuscularly (IM) or subcutaneously (SC), but very little is known about its efficacy when administered via a mucosal route. We hypothesized that Ad5-A24 could induce mucosal immunity and that immune response could be enhanced when this vaccine is coadministered with Ad5-vectored E. coli heat labile enterotoxin as a mucosal adjuvant. Specifically, four different LT-mutants (LTK63, LTR72, and LTB) were cloned into Ad5-vector and were tested in animals after intranasal (IN) administration.

After two IN inoculations of Ad5-A24 + Ad5-LTR72, mice were protected against a lethal challenge of homologous FMDV. Furthermore, pigs inoculated with Ad5-A24 + Ad5-LTR72 IN and boosted IM were better protected than pigs inoculated IN-IN, after an overwhelming challenge of FMDV A24. Further evaluation of specific immune response as well as the protective efficacy of Ad5-LTR72 should be addressed with the appropriate challenge dose. Overall, this new approach of FMDV vaccination showed promising results and could be an efficient strategy in FMDV control and eradication.

Available for download on Saturday, April 27, 2024

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