Footrot Vaccine Research Articles

O-124 Impact of bivalent and multivalent footrot vaccines on antibiotic usage for lameness in breeding ewes

O-124 Impact of bivalent and multivalent footrot vaccines on antibiotic usage for lameness in breeding ewes

Characterization of two putative Dichelobacter nodosus footrot vaccine antigens identifies the first lysozyme inhibitor in the genus

The Gram-negative anaerobic bacterium Dichelobacter nodosus (Dn) causes footrot in ruminants, a debilitating and highly contagious disease that results in necrotic hooves and significant economic losses in agriculture. Vaccination with crude whole-cell vaccine mixed with multiple recombinant fimbrial proteins can provide protection during species-specific outbreaks, but subunit vaccines containing broadly cross-protective antigens are desirable. We have investigated two D. nodosus candidate vaccine antigens. Macrophage Infectivity Potentiator Dn-MIP (DNO_0012, DNO_RS00050) and Adhesin Complex Protein Dn-ACP (DNO_0725, DNO_RS06795) are highly conserved amongst ~170 D. nodosus isolates in the https://pubmlst.org/dnodosus/ database. We describe the presence of two homologous ACP domains in Dn-ACP with potent C-type lysozyme inhibitor function, and homology of Dn-MIP to other putative cell-surface and membrane-anchored MIP virulence factors. Immunization of mice with recombinant proteins with a variety of adjuvants induced antibodies that recognised both proteins in D. nodosus. Notably, immunization with fimbrial-whole-cell Footvax vaccine induced anti-Dn-ACP and anti-Dn-MIP antibodies. Although all adjuvants induced high titre antibody responses, only antisera to rDn-ACP-QuilA and rDn-ACP-Al(OH)3 significantly prevented rDn-ACP protein from inhibiting lysozyme activity in vitro. Therefore, a vaccine incorporating rDn-ACP in particular could contribute to protection by enabling normal innate immune lysozyme function to aid bacterial clearance.

Impact of footrot vaccination and antibiotic therapy on footrot and contagious ovine digital dermatitis

Footrot and contagious ovine digital dermatitis (CODD) are common causes of foot disease of sheep in the UK. The study reported here is a split flock randomised treatment trial undertaken...

Modulation of inter-vaccination interval to avoid antigenic competition in multivalent footrot ( Dichelobacter nodosus) vaccines in sheep

Virulent footrot is a significant disease of sheep in most sheep farming countries; a strain/serogroup of the anaerobic bacterium Dichelobacter nodosus is the essential transmitting agent. Commercial multivalent footrot vaccines containing nine fimbrial serogroups (A through I) of D. nodosus produce relatively low and short term antibody responses due to antigenic competition, in contrast to higher and longer responses provided by monovalent or bivalent vaccines. The latter were important components of successful eradication programs for endemic footrot caused by either one or two serogroups of D. nodosus in Nepal, Bhutan, and several flocks in Australia. However, the presence of up to six serogroups in some Australian flocks and the use of an annual bivalent vaccination regime to progressively eradicate serogroups would require a long term program. In this study we report the results of a sequential vaccination trial testing different time intervals between different bivalent vaccinations. Intervals of 12, 9, 6, 3 and 0 months were tested. The 1st vaccination was with recombinant fimbrial antigens for serogroups A and B while the 2nd vaccination was with D and E. There were no significant differences between the antibody responses for time intervals of 3, 6, 9 and 12 months whereas there was a reduced response when sheep were vaccinated with two bivalent vaccines (four antigens) concurrently, indicating antigenic competition. Therefore an inter-vaccination interval of 3 months can be applied between two different bivalent vaccines without detrimental impact on the humoral immune responses to the various fimbrial antigens of D. nodosus. These results could have wider applications in vaccination against diseases caused by multivalent or multistrain microbes.

Evolution of oxidative/nitrosative stress biomarkers during an open-field vaccination procedure in sheep: Effect of melatonin

Melatonin has been shown to exert immunomodularory properties with broad application in veterinary medicine. In previous work we have described that subcutaneous coadministration of melatonin to seeps vaccinated against two stumps of A1 and C strains of Dichelobacter nodosus enhanced both the antibody titer and serum IgG levels to A1 and C strains of D. nodosus compared to vaccinated animals not treated with melatonin. Following a similar protocol here we have investigated the effect of a higher dose of melatonin (36 mg/animal) in the improvement of the immune response and in the possible oxidative/nitrosative stress produced during the immunization protocol. Our results show that footrot vaccine application induced nitrosative but not oxidative stress at 42 days post-vaccination, which was neutralized by melatonin administration. On the other hand, melatonin improved the immune response with respect to our previous data increasing the time of permanence of antibodies in serum, opening new perspectives for melatonin as prophylactic drug.

Immunological parameters associated with antigenic competition in a multivalent footrot vaccine

A murine model for antigenic competition with multivalent D. nodosus pili vaccine has been established that parallels the phenomenon observed in sheep where levels of antibody, specific for any particular serogroup of pili, are significantly lower following vaccination in the presence of multiple serogroups of pili than with that serogroup alone. This competition was observed in both high and low responder strains of mice and was not dependent on the multiplicity of the antigens in the multivalent vaccine but could be observed with a large excess of a single heterologous serogroup. Competition was manifest by a reduction in the number of serogroup-specific antibody secreting cells elicited in response to vaccination. The antibody response to a single serogroup of pili reached a plateau at high doses and it was at these doses that antigenic competition was most pronounced, under conditions where both B- and T-cell responses were limiting. The limit in T-cell responsiveness was not imposed at the level of presentation of antigen. Pili-specific T cells were largely cross-reactive for different serogroups, and under conditions of limiting T-cell stimulation within a lymph node the available T cells would have to be shared between B cells specific for each serogroup of pili, which may in turn result in the decrease of serogroup-specific antibody induced following inoculation with the multivalent vaccine.

Application of ELISA to the serological diagnosis of virulent ovine footrot

The sensitivity and specificity of an ELISA that detects antibody in the serum of sheep against Dichelobacter nodosus was investigated. The sensitivity of the assay was determined in two trials in which sheep free of virulent footrot were exposed to a virulent strain of D. nodosus. In the first trial up to 96.6% of sheep that developed severe foot lesions were seropositive 2 weeks later. The proportion of seropositive sheep depended on the interval between exposure to D. nodosus and collection of blood samples and reached a maximum 6 weeks after exposure in the first trial and plateaued from 8 weeks after exposure in the second trial. of sheep with severe lesions present for only 1 week, 40.0% became seropositive, while 98.3% of sheep with severe lesions present for 3 or more weeks became seropositive in Trial 1. Of the unexposed control sheep from the same flock, 93.3% remained seronegative. At least 75% of sheep that were vaccinated with commercial footrot vaccines remained seropositive for at least 24 months after last vaccination and 58.5% remained seropositive for at least 36 months. The specificity of the assay in flocks of sheep from different geographical regions was determined also. Overall, 95.2% of 2978 sheep free of virulent footrot were seronegative. However the rate of false positive serological reactions ranged from 1.6% to 11.3% between flocks and was higher in older sheep (7.0%) compared with sheep less than 1.5 years old (2.7%). Passively acquired colostral antibodies against D. nodosus were measured in 22 lambs and did not persist beyond 55 days mean age. Non-specific reactions with cross reactive antigens were proposed to explain age related changes in serological results. Applications of this ELISA in footrot control programmes are discussed.

Recombinant vaccines against ovine footrot.

For the past 20 years footrot vaccines have evolved from simple bacterins to highly specific recombinant DNA (rDNA) fimbrial vaccines. The development of these vaccines has left a trail of discoveries, challenges and solutions; these processes continue as we move closer to understanding the requirements of a footrot vaccine. The initial whole cell vaccines were unsuccessful due to the short duration of immunity and incorporation of limited serotypes. A multistrain vaccine eliminated the problem of serotype inclusion, although the duration of immunity in many cases is still inadequate. The proteases of Dichelobacter nodosus appear to be cross protective; however, little is known of their ability to protect sheep against footrot. The major protective immunogen is the bacterial fimbriae, which also forms the basis for the K-agglutination serotyping system. K-agglutinin titre correlates directly with resistance to challenge. The protective fimbrial epitope is conformationally dependent, suggesting little advantage in the development of synthetic peptide vaccines. To enhance the efficiency of vaccine production D. nodosus fimbrial genes were eventually cloned and successfully expressed in Ps. aeruginosa. Monovalent vaccines based on recombinant fimbriae are omnipotent, inducing high levels of agglutinins and long lasting immunity. In multivalent vaccines, on the other hand, incorporation of each additional serogroup into the vaccine results in reduced efficacy both in terms of reduced K-agglutinin titres and reduced protection following challenge. The least effective are multivalent formulations representing all major serogroups. In addition, considerable genetic variation has been observed in the ability of sheep to respond optimally to each serogroup in a multivalent vaccine. Results show that the limitation of the sheep to mount an effective immune response, rather than the quality or quantity of the immunogen, limits the efficacy of current footrot vaccines. Studies are being undertaken to examine in detail the immune response of sheep to potentially highly effective footrot vaccines.

The effect of time between doses on serological response to a recombinant multivalent pilus vaccine against footrot in sheep

The response of sheep to a recombinant multivalent footrot vaccine containing pilus antigens was examined after the administration of two doses of vaccine at intervals ranging from 2 to 52 weeks. Agglutinating antibody titres were measured 3 weeks after the second vaccination and showed that lengthening of the interdose interval results in higher agglutinin titres. The capability of sheep to mount an increasingly strong immune response as the interval between doses is increased provides an opportunity to maximise the usefulness of vaccination by administering the first dose well before an expected footrot transmission period. This advantage of increasing the interdose interval has not been reported for traditional, whole-cell footrot vaccines, and use of the new pilus vaccine in this manner may improve prospects for disease control. Furthermore, sheep given a third dose either 6 or 12 months after their initial two-dose vaccination program achieved significantly higher titres than those elicited after the second dose, suggesting the likelihood of further improvement in disease control in successive seasons.

The effects of antigenic competition on the efficacy of multivalent footrot vaccines.

A multivalent footrot vaccine has been developed, containing pilus antigens produced in recombinant Pseudomonas aeruginosa and representing all nine serogroups of Dichelobacter (Bacteroides) nodosus commonly recognised in the field. The responses of sheep to the multivalent vaccine have been compared with those to monovalent vaccines representing only a single serogroup. Antigenic competition between serogroups occurred in sheep immunised with the multivalent formation, but high levels of protection were still achieved. The study showed that in multivalent footrot vaccines, antigenic competition is predominantly due to the presence of a family of immunologically-related pilus antigens rather than to interference by extraneous proteins.

Antigenic profiles of Bacteroides nodosus strains isolated from sheep given a polyvalent commercial footrot vaccine

The 20 Bacteroides nodosus serotypes (I–XX) known to occur in the United States were compared by serum tube agglutination to the eight British serotypes (A–H) of B. nodosus contained in a commercial footrot vaccine. Fourteen of the U.S. serotypes reacted with antisera generated against the vaccine serotypes. There was no U.S. counterpart to type E. The vaccine was administered to a herd of sheep infected with footrot. B. nodosus isolates from vaccinated and non-vaccinated sheep were serotyped and compared to the vaccine serotypes. The four serotypes of B. nodosus identified in the herd (I, V, X and XV) were antigenically similar to, or identical with, four serotypes contained in the commercial vaccine (A, D, F and H). However, in the case of U.S. serotype X this relationship was only seen with the U.S. antigen and British antiserum, not the reciprocal reaction. This information implies that footrot vaccines for use in the U.S. could possibly be more efficacious if they were produced from U.S. serotypes rather than British serotypes.

A positive association between resistance to ovine footrot and particular lymphocyte antigen types.

The distribution of 12 Class I ovine lymphocyte antigens (OLA) was examined in 4 flocks of sheep vaccinated against and/or challenged with Bacteroides nodosus, the transmitting agent of footrot. In a flock of 47 Corriedales in New Zealand, which had been specially bred for resistance to footrot, a higher frequency (70.2%) of OLA type SY6 was found compared with 42.9% in 49 unselected Corriedale sheep (P = 0.001). The serum antibody response of 12 selected Corriedale ewes was compared with that of 12 unselected ewes of the same age after vaccination with a multivalent footrot vaccine and the selected ewes had significantly (P = 0.01) higher agglutinin titres than the unselected ewes, 7 weeks after vaccination. In 3 trials involving 108, 120 and 135 Australian Merinos in Victoria, SYlb was associated with a reduction in the number of feet affected with severe footrot (P = 0.05, P = 0.01, P = 0.02) and in 2 of the trials there was a relationship between SY6 and high vaccinal agglutinin titres. This SY6 effect was evident in the first trial 31 days after primary vaccination (P = 0.05) and again 20 days later after secondary vaccination (P = 0.01). In the second trial, when the sheep were vaccinated 49 days after challenge, an association was again found between SY6 and high agglutinin titres (P = 0.05) after primary but not after secondary vaccination. Exposure of 157 vaccinated Merino rams to B. nodosus during a footrot outbreak in New South Wales also showed an association between low infection and SY6 and SYlb.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of ovine virulent footrot with zinc sulphate/sodium lauryl sulphate footbathing.

Trials were conducted on 2 commercial sheep flocks in the Gippsland region of Victoria to determine the efficacy of treating ovine virulent footrot by footbathing in aqueous zinc sulphate solution (20% w/v). The effects of foot paring, parenteral penicillin, vaccination and addition of sodium lauryl sulphate (SLS) to the footbaths were assessed. Trial 1 comprised 297 sheep with an initial prevalence of footrot of 33% and most lesions were severe and chronic. Treatment of sheep with unpared feet by zinc sulphate footbathing for 1h did not result in a significant reduction in footrot prevalence (n = 120, cure rate 33%) whereas a significant (P less than 0.01) response was obtained by footbathing for 1h with zinc sulphate/SLS (n = 120, cure rate 55%). Trial 2 comprised 1,042 sheep with a pretreatment footrot prevalence of 71% and predominantly severe lesions. In this flock all treated sheep were footbathed in zinc sulphate/SLS for 1h on 2 occasions, 5 days apart and the effects of additional surgical and parenteral treatments were assessed. Foot paring had a significant detrimental effect on cure rate (P less than 0.01). The administration of procaine penicillin at the time of the first footbathing with zinc sulphate/SLS made no significant improvement to the rate of cure. Footrot vaccine given 8 and 2 weeks prior to footbathing did not cure significantly more sheep than footbathing alone, but the results were significantly better than from foot paring plus footbathing, and from combined foot paring, footbathing and parenteral penincillin treatment (P less than 0.01). The cure rate was 84% for sheep that were only footbathed, 72% for those foot pared and footbathed, 72% for those foot pared, footbathed and given penicillin, and 88% for those vaccinated and footbathed.

Vaccination against lumpy jaw and measurement of antibody response in wallabies (Macropus eugenii).

Successful protection against lumpy jaw disease in a colony of captive wallabies (Macropus eugenii) was induced by vaccination with a commercial ovine footrot vaccine. No mortalities attributable to lumpy jaw were observed in 69 vaccinated animals while six of 42 unvaccinated control wallabies died of the disease. Vaccinated animals exhibited significant increases in antibody titres to Bacteroides nodosus after the first and second doses of vaccine. Titres were measured by an enzyme-linked immunosorbent assay.

Field trials with a killed, nine-strain, oil adjuvantedBacteroides nodosusfootrot vaccine in sheep

Field trials were set up on five properties to determine the cure and protection rates of a killed, nine-strain, oil adjuvanted Bacteriodes nodosus footrot vaccine, under natural conditions. Foot infections were scored at the time of the first vaccination and at approximately four weeks and ten weeks later. Cure rates were 34-47% for vaccinated sheep, and 18-47% for untreated sheep. Using the Australian Licensing Authorities calculation, the cure rates for the vaccine ranged from -40% to 44%. A lack of suitable conditions for spread of footrot meant that protection rates could not be determined.

Injection site lesions of footrot vaccines in sheep

Three trials were conducted to assess the size and frequency of lesions induced by an oil-based and an alum-precipitated aqueous B. nodosus commercial footrot vaccine at two injection sites (neck and brisket) with or without prior skin swabbing with methanol. Animals used were previously unvaccinated and clean and dry at time of vaccination. Trial 1 contained 57 2-tooth Booroola Merino x Coopworth ewes, trial 2 contained 60 mixed-age Corriedale ewes, and trial 3 contained 39 rams of mixed age and sex. Firm nodules or plaques with indurated edges and with a maximum dimension of 1cm or more appeared soon after vaccination and were still very common (50-100% of sheep vaccinated) 5-6 weeks after injection. A variable proportion exhibited a liquefied central area of necrosis and later discharged necrotic material. The oil-based vaccine produced significantly larger lesions than the alum-precipitated aqueous vaccine. Lesion size at the brisket site was significantly larger than the neck site in ewes but not in rams. Skin preparation with methanol had no effect on lesion frequency or size.

Hypersensitivity to foot-rot vaccine

Hypersensitivity to foot-rot vaccine

Hypersensitivity to foot-rot vaccine

Hypersensitivity to foot-rot vaccine