Duration of protection and immunity induced by an adenovirus- vectored foot-and-mouth disease virus serotype A24 subunit vaccine in Holstein steers

Authors: SITT, TATJANA - University Of Vermont; Kenney, Mary; BARERRA, JOSE - Leidos; PANDYA, MITAL - University Of Vermont; ECKSTROM, KORIN - University Of Vermont; WARNER, MEGAN - Oak Ridge Institute For Science And Education (ORISE); PACHECO, JUAN - Former ARS Employee; LAROCCO, MICHAEL - Retired ARS Employee; BRAKE, DAVID - Bioquest Associates, Llc; Rieder, Aida - Elizabeth; Arzt, Jonathan; BARLOW, JOHN - University Of Vermont; GOLDE, WILLIAM - The Moredun Group

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/13/2019
Publication Date: N/A
Citation: N/A

Interpretive Summary: Foot-and-mouth disease (FMD) a devastating disease of livestock, continues to be one of the major threats to US agriculture. Existing vaccines require the use of live pathogenic virus for vaccine production. A safer vaccine made using an attenuated human cold virus (called Adenovirus 5 or Ad-5) was licensed for US production in 2012. This is the first molecular-based FMD vaccine (ad5-FMD) that could be manufactured in the US and is safe for use in meat and milk-producing livestock. This vaccine was shown to protect cattle as soon as 7 days post vaccination and for at least 21 days thereafter. However, the duration of this protective response was unknown. Here we report the results of three independent vaccine challenge experiments in cattle examining the long-term performance of the Ad-5-FMD vaccine and using different routes of injection. Our results demonstrate that the vaccine is effective for up to 6 months. However, by 9 months, some of the vaccinated animals were not protected and showed disease signs. Further research is necessary to improve the duration of immunity of the Ad5-FMD vaccine.

Technical Abstract: The importance of an efficacious, long acting foot-and-mouth disease (FMD) vaccine is critical to control FMD, one new vaccine technology that has proven to be particularly promising is the human replication deficient adenovirus 5 (Ad5) empty capsid FMDV platform (AdtFMD). Herein we describe three studies assessing the proportion of animals protected from clinical vesicular disease (foot lesions) following live-virus challenge by intradermolingual inoculation at 6 or 9 months following a single vaccination, assessment of FMDV-specific immunologic memory as potential predictors of protection, and the potential effect of vaccination route (transdermal, intramuscular, subcutaneous) on outcome. Results demonstrate single dose vaccination in cattle using AdtA24 induced 6 months protection against clinical FMD (100% transdermal, 80% intramuscular, and 60% subcutaneous) that waned by 9 months post-vaccination (33% transdermal and 20% intramuscular). Post-vaccination, serum from vaccinated steers (all studies) contained FMDV specific neutralizing antibodies generally by day 14. On average, vaccinated steers produced higher virus neutralization titers post-vaccination in the 6 month studies 1 (p<0.001) and 3 (p<0.001) compared to the 9 month study, 2. Overall, only the number of IgG1 antibody secreting cells were significantly increased in vaccinated steers compared to placebo-immunized controls (p=0.007). The decay in protective immunity over time may be a function of FMDV-specific antibody half-life due to loss of antibody secreting cells in circulation. This is the first study to demonstrate FMDV experimental challenge protection in cattle following transdermal vaccination with a recombinant vectored subunit vaccine using a needle-free delivery system. Additionally, this study demonstrates that utilizing a non-BSL-3Ag off-site facility for initial vaccination, followed by transport to and challenge in a BSL-3 Ag research facility is feasible, though animal husbandry and management criteria must be considered.