Efficacy of an adenovirus-vectored foot-and-mouth disease virus serotype A subunit vaccine in cattle using a direct contact transmission model

John G Neilan,Laszlo Zsak,José Barrera,Melia Pisano,Christopher Schutta,Max V Rasmussen,David A Brake,Douglas E Brough,Bryan T Butman,Ethan Hartwig,Barbara J Kamicker,Damodar Ettyreddy

doi:10.1186/s12917-018-1582-1

John G Neilan, Laszlo Zsak + Show 10 more

Open Access

https://doi.org/10.1186/s12917-018-1582-1

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Abstract

BackgroundA direct contact transmission challenge model was used to simulate natural foot-and-mouth disease virus (FMDV) spread from FMDV A24/Cruzeiro/BRA/55 infected ‘seeder’ steers to naïve or vaccinated steers previously immunized with a replication-deficient human adenovirus-vectored FMDV A24/Cruzeiro/BRA/55 capsid-based subunit vaccine (AdtA24). In two independent vaccine efficacy trials, AdtA24 was administered once intramuscularly in the neck 7 days prior to contact with FMDV A24/Cruzeiro/BRA/55-infected seeder steers.ResultsIn Efficacy Study 1, we evaluated three doses of AdtA24 to estimate the 50%/90% bovine protective dose (BPD50/90) for prevention of clinical FMD. In vaccinated, contact-challenged steers, the BPD50/90 was 3.1 × 1010 / 5.5 × 1010 AdtA24 particles formulated without adjuvant. In Efficacy Study 2, steers vaccinated with 5 × 1010 AdtA24 particles, exposed to FMDV A24/Cruzeiro/BRA/55-infected seeder steers, did not develop clinical FMD or transmit FMDV to other vaccinated or naïve, non-vaccinated steers. In contrast, naïve, non-vaccinated steers that were subsequently exposed to FMDV A24/Cruzeiro/BRA/55-infected seeder steers developed clinical FMD and transmitted FMDV by contact to additional naïve, non-vaccinated steers. The AdtA24 vaccine differentiated infected from vaccinated animals (DIVA) because no antibodies to FMDV nonstructural proteins were detected prior to FMDV exposure.ConclusionsA single dose of the AdtA24 non-adjuvanted vaccine conferred protection against clinical FMD at 7 days post-vaccination following direct contact transmission from FMDV-infected, naïve, non-vaccinated steers. The AdtA24 vaccine was effective in preventing FMDV transmission from homologous challenged, contact-exposed, AdtA24-vaccinated, protected steers to co-mingled, susceptible steers, suggesting that the vaccine may be beneficial in reducing both the magnitude and duration of a FMDV outbreak in a commercial cattle production setting.

Highlights

A direct contact transmission challenge model was used to simulate natural foot-and-mouth disease virus (FMDV) spread from FMDV A24/Cruzeiro/BRA/55 infected ‘seeder’ steers to naïve or vaccinated steers previously immunized with a replication-deficient human adenovirus-vectored FMDV A24/Cruzeiro/BRA/55 capsid-based subunit vaccine (AdtA24)
We recently reported that a replication deficient, recombinant human adenovirus serotype 5 vectored (Ad5) adjuvant-free vaccine co-expressing the P1 capsid from FMDV A24/Cruzeiro/ BRA/55 and 3C protease genes of FMDV A12/119/Kent/ UK/32 (AdtA24) was efficacious at 7 dpv in cattle using a intradermolingual (IDL) direct challenge model [15] and enabled differentiate infected from vaccinated animals (DIVA) prior to challenge
In T1-T3 vaccinates, protection against clinical Foot-and-mouth disease (FMD) was vaccine dose-dependent, since 50% of T1 high dose vaccinates were completely protected compared to 33% and 0% of T2, medium dose, and T3, low dose, vaccinates

Summary

Introduction

A direct contact transmission challenge model was used to simulate natural foot-and-mouth disease virus (FMDV) spread from FMDV A24/Cruzeiro/BRA/55 infected ‘seeder’ steers to naïve or vaccinated steers previously immunized with a replication-deficient human adenovirus-vectored FMDV A24/Cruzeiro/BRA/55 capsid-based subunit vaccine (AdtA24). In FMD-free countries, generation recombinant FMD vaccines produced without the use of virulent FMDV strains are more advantageous than inactivated vaccines, especially for a rapid response against newly emerging FMDV topotypes/viral lineages that are a poor antigenic match against current vaccines. The FMDV capsid gene sequence from an outbreak strain can be obtained following virus isolation, rapidly synthesized, and inserted into a standardized viral-vector vaccine production platform. The AdtA24 described below, based on the AdtFMD vaccine platform, is genetically deleted in antibody epitopes used in current FMD serological diagnostic tests and can differentiate infected from vaccinated animals (DIVA)

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