Efficacy of a high potency O1 Manisa monovalent vaccine against heterologous challenge with foot-and-mouth disease virus of O/SEA/Mya-98 lineage in sheep

Abstract

Potency tests for commercial oil-adjuvanted foot-and-mouth disease (FMD) vaccines are usually carried out in cattle, using a full dose (2 ml) of vaccine and homologous virus challenge. However, in sheep the recommended vaccine dose is half of the cattle dose (1 ml) and most vaccines have not been potency tested for this species, especially with heterologous viruses. To determine the efficacy of a high potency (>6PD) FMD virus (FMDV) O1Manisa vaccine in sheep, we carried out a study using a heterologous FMDV (FMDV O/SKR/2010 - Mya-98 strain) challenge. Groups of seven animals each were vaccinated with 2×, 1×, 1/2× or 1/4× dose (2 ml, 1 ml, 0.5 ml or 0.25 ml respectively) and challenged at 7 days post vaccination (dpv). Only 3 of the 7 sheep in the group vaccinated with 2 ml were protected. With 2 additional groups, receiving double or single doses and challenged at 14 dpv, 4 of 7 sheep were protected in each group. None of the sheep had measurable neutralising antibodies against the vaccine or challenge virus at 7 dpv. However, all vaccinated animals challenged at 14 dpv had a homologous neutralising response against FMDV O1 Manisa on the day of challenge and all but one animal also had a heterologous response to FMDV O/SKR/2010. Infectious FMDV and viral RNA could be found in nasal swabs between 1 and 6 days post challenge (dpc) in most vaccinated sheep, but those vaccinated with higher doses or challenged at 14 dpv showed significant decreases in the level of FMDV detection. Intermittent virus shedding was noticed between 1 and 35 dpc in all vaccinated groups, but persistent infection could be demonstrated only in 4 sheep (20%). This study showed that at the recommended dose, a high potency (>6 PD) FMDV O1Manisa vaccine does not protect sheep against a heterologous challenge at 7 dpv. However, partial protection was observed when a double dose was used at 7 dpv or when double or single dose vaccinated sheep were challenged at 14 dpv.

Virulence beneath the fleece; a tale of foot-and-mouth disease virus pathogenesis in sheep

“…The samples used for the current investigation originated from two separate experiments that have been previously published [5,36]. Both experiments were carried out at the Plum Island Animal Disease Center (PIADC), New York.…”

“…Experiment 2. Sheep for the second part of the study came from an earlier study that assessed the efficacy of a high-potency FMDV O1 Manisa vaccine (>6 50% Protective Doses [PD 50 ] per dose) against heterologous challenge [36]. These animals had received a single-dose of vaccine (1ml of a normal 2ml cattle dose) at 14 days before challenge (single dose/14d) or a double-dose of vaccine (2ml) at 7 or 14 days before challenge (double dose/7d, double dose/ 14d).…”

“…These animals had received a single-dose of vaccine (1ml of a normal 2ml cattle dose) at 14 days before challenge (single dose/14d) or a double-dose of vaccine (2ml) at 7 or 14 days before challenge (double dose/7d, double dose/ 14d). All sheep were challenged by coronary band injection in one foot, and the clinical outcome of the study has been published earlier [36]. Detailed post-mortem tissue sampling was carried out on a subset of animals (n = 10) at 35-37 days post-challenge (dpc) for the objective of investigating tissue distribution of FMDV in sheep during persistent infection.…”

“…The objective of this current investigation was to update the understanding of the anatomic distribution of FMDV in sheep during both early and late stages of infection, by use of experimental models optimized for FMDV pathogenesis studies in cattle and pigs. The current investigation included animals derived from two separate experimental studies originally designed for separate objectives: 1) evaluating different inoculation-and exposure systems for FMDV studies in sheep [5], and 2) investigating heterologous vaccine protection [36]. Sheep selected for the current study were euthanized for post-mortem tissue harvest at pre-determined time points during early or persistent stages of infection.…”

The Carrier Conundrum; A Review of Recent Advances and Persistent Gaps Regarding the Carrier State of Foot-and-Mouth Disease Virus

“…This finding was similar across naïve and vaccinated cohorts of sheep. However, the administration of a high payload vaccine (> 6 PD 50 ) 14 days prior to virus challenge prevented FMDV persistence, even though all animals were confirmed to have been infected after challenge [29,78]. The combined output of FMDV pathogenesis studies in sheep thus suggest that although virus detection during early infection shares similarities with both cattle and pigs, the anatomic localization of persistent FMDV may be more similar to infection in African buffalo.…”