Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits low immunogenicity in psoriasis patients treated up to 5 years.

BACKGROUND: Secukinumab is a fully human monoclonal antibody that selectively neutralizes IL-17A, a key cytokine involved in psoriasis and psoriatic arthritis development, and has shown rapid and long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations. Monoclonal antibody therapies may be associated with the production of treatment-emergent antidrug antibodies (TE-ADAs) that can affect drug pharmacokinetics, diminish clinical responses via inhibition of target binding or cause hypersensitivity reactions. Secukinumab exhibited minimal immunogenicity up to 52 weeks in patients with moderate-to-severe plaque psoriasis, as evidenced by TE-ADA in <1% patients. OBJECTIVE: To investigate the immunogenicity of secukinumab treatment up to 5 years in two phase 3 extension studies (NCT01640951 and NCT01365455) in patients with moderate-to-severe plaque psoriasis. METHODS: Immunogenicity was evaluated up to Week 268 (5 years). TE-ADAs were defined as positive antidrug antibody (ADA) signals detected in post-treatment samples from patients with negative baseline signals. Confirmed positive samples were further analysed for their neutralizing potential. RESULTS: In total, 1821 patients entered the extension studies. Among patients receiving secukinumab and evaluated for ADAs (n = 1636), 32 developed TE-ADA, which resulted in an incidence of new TE-ADA cases below 1% per year. Neutralizing antibodies were detected in 9/32 (28%) patients with TE-ADA. Half of ADA-positive cases were transient. Among pharmacokinetic samples measured at the times of immunogenicity determination (n = 9992), 544 (5.4%) had secukinumab concentrations higher than the drug tolerance level of 53.8 µg/mL. There was no effect of TE-ADA, including neutralizing antibodies, on efficacy, safety or pharmacokinetics of secukinumab. CONCLUSION: The yearly secukinumab immunogenicity incidence over 5 years of treatment was consistently below 1% in patients with moderate-to-severe plaque psoriasis. Any TE-ADAs, including neutralizing antibodies, were not associated with loss of secukinumab efficacy or with clinical concerns.

Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits minimal immunogenicity in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: The proinflammatory cytokine interleukin (IL)-17A plays a pivotal role in psoriasis pathogenesis. Secukinumab, a fully human monoclonal antibody (mAb) that selectively targets IL-17A, has been demonstrated to be highly efficacious for the treatment of moderate-to-severe psoriasis, starting at early time points, with a sustained effect and a favourable safety profile. mAb therapies may be associated with production of antidrug antibodies (ADAs) that can affect drug pharmacokinetics, diminish response or cause hypersensitivity reactions. OBJECTIVES: To investigate the immunogenicity of secukinumab across six phase III clinical trials in which patients with plaque psoriasis were treated with secukinumab for up to 52 weeks and additionally followed up at week 60. METHODS: Immunogenicity in patients with plaque psoriasis exposed to secukinumab was evaluated at baseline and at weeks 12, 24, 52 and 60. Treatment-emergent (TE)-ADAs were defined as a positive ADA signal detected in post-treatment samples from patients with a negative baseline signal. Confirmed positive samples were further analysed for their drug-neutralizing potential. RESULTS: Among 2842 patients receiving secukinumab and evaluated for ADAs, 11 (0·4%) developed TE-ADAs. Associations between TE-ADAs and secukinumab dose, frequency or mode of administration were not observed. Neutralizing antibodies were detected in three of nine evaluable patients with TE-ADAs. CONCLUSIONS: Secukinumab immunogenicity was low, as shown by TE-ADA detection in only 11 of 2842 (0·4%) patients with moderate-to-severe plaque psoriasis treated with secukinumab. All but one of the patients with TE-ADAs were biologic naive. Neither TE-ADAs nor neutralizing antibodies were associated with loss of secukinumab efficacy or issues of clinical concern.

Langerhans' cells, veiled cells, and interdigitating cells in the mouse recognized by a monoclonal antibody.

An mAb, NLDC-145, is described that specifically reacts with a group of nonlymphoid dendritic cells including Langerhans cells (LC), veiled cells (VC), and interdigitating cells (IDC). The antibody does not react with precursor cells in bone marrow and blood. Macrophages are not stained by the antibody, but a subpopulation of Ia+ peritoneal exudate cells is recognized. Possible relationships of the various nonlymphoid dendritic cell (NLDC) types are discussed.

Influence of environmental temperature on mitochondrial membranes.

Mitochondrial phospholipids from goldfish lateral line muscle were analysed with respect to polar and apolar groups. Groups of 20 goldfish, acclimated to 5, 20 and 30 degrees C, were used. Temperature-induced shifts of both polar and apolar groups of the mitochondrial phospholipids were observed. The fatty acid composition of mitochondrial phospholipids is characterized by a large amount of polyenoic acids, dominated by docosahexaenoic acid and by octadecadienoic acid. At the higher acclimation temperatures, a significant decrease in docosahexaenoic acid is found. However, the resultant effect of environmental temperature on the degree of unsaturation is small, in contrast to the marked effect on mean chain length. Pronounced changes in the molar ratio of phosphatidylcholine and phosphatidylethanolamine are seen; a decrease in mitochondrial phosphatidylcholine is observed at low acclimation temperature, which is compensated for by a nearly equal increase in phosphatidylethanolamine. The main phospholipids are, apparently, phosphatidylcholine, phosphatidylethanolamine and cardiolipin, comprising 90% of the total pool of 12 species. It is found that the anionic nature of the phospholipids is increased at low acclimation temperatures. We discuss this effect and its probable importance in the stabilization of the surface potential of the mitochondrial membranes.

Chaotropic resolution of high molecular weight (type I) NADH dehydrogenase, and reassociation of flavin-rich (type II) and flavin-poor subunits.

1. Type-I NADH dehydrogenase (Complex I) was solubilized and dissociated into subunits by NaClO4. NADH slows the dissociation. On subsequent stepwise addition of (NH4)2SO4 the dissociation is partly reversed, as is to be expected from the opposing effects of ClO-4 and SO-24, which are on the salting-in and salting-out sides, respectively, of the lyotropic series. 2. In consequence, the aggregates of subunits that are separated by (NH4)2-SO4 fractionation consist of randomly associated subunits as well as fragments of Type I enzyme. The fraction precipitating at 27% satd. (NH4)2SO4 is flavin-poor, that remaining soluble at 55% satd. (NH4)2SO4 flavin-rich and those separating between 27 and 55% satd. (NH4)2SO4 intermediate in composition. 3. The fraction remaining soluble at 55% satd. (NH4)2SO4 contains the purified low-molecular-weight iron-sulphur flavoprotein (Type-II dehydrogenase). It is a dimer consisting of one molecule of FMN, one 28-kilodalton and one 56-kilodalton subunit per protomer. Work of others indicates that it contains 4 Fe and 4 acid-labile S atoms per molecule of FMN. Sometimes the fraction remaining soluble at 55% satd. (NH4)2SO4 contained an additional small subunit (12 kilodaltons) and four additional Fe and acid labile S atoms per protomer. The sedimentation coefficients (s020,w) of the two preparations were 5.3 and 6.6 S, respectively, with calculated frictional ratios of 1.5 and 1.24, respectively. 4. The intermediate fractions are mixtures of the various subunits present in Complex I. Specifically a fraction separating at 55% satd. (NH4)2SO4 was found to be a mixture of two fragments, the pure iron-sulphur flavoprotein and a 26-S fragment that contained per protomer four subunits of 12 kilodaltons, one each of 28, 32, 56 and 77 kilodaltons, one molecule of FMN and 20 Fe and acid-labile S atoms. It was probably tetrameric or even larger. 5. The oxidoreductase activity of the intermediate fractions is dependent on the protein concentration, the activity with ferricyanide increasing and that with ferricytochrome c decreasing with increasing protein concentration. This is interpreted as an increased association of subunits present in the intermediate fractions. Similar results are obtained when flavin-rich and flavin-poor fractions are mixed. The association is cooperative. NADH favours the association of the subunits. 6. Association of the subunits is accompanied by a 10-fold increase in k2 (rate constant for intramolecular electron flow), a 10-fold decrease of the accessibility of ferricyanide to the reduced enzyme and a 10(4)-fold decrease of the accessibility of ferricytochrome c. The Ks (NADH) is also decreased. Although the changes are in the direction to be expected from a conversion of Type II enzyme to Type I, the value of k2 is still much less than in the latter enzyme.

Population PK-PD Model for Tolerance Evaluation to the p38 MAP Kinase Inhibitor BCT197.

The p38 mitogen-activated protein kinase (p38) is a key signaling pathway involved in regulation of inflammatory cytokines. Unexpectedly, several clinical studies using p38 inhibitors found no convincing clinical efficacy in the treatment of chronic inflammation. It was the objective of this study to characterize the population pharmacokinetics (PK) of BCT197 in healthy volunteers and to examine the relationship between BCT197 exposure and pharmacodynamics (PD) measured as inhibition of ex vivo lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNFα), a downstream marker of p38 activity. PK was characterized using a two-compartment model with mixed-order absorption and limited-capacity tissue binding. The PK-PD relationship revealed that suppression of TNFα was partly offset over time, despite continuous drug exposure. This may indicate a mechanism by which the inflammatory response acquires the ability to bypass p38. Simulations of posology dependence in drug effect suggest that an intermittent regimen may offer clinical benefit over continuous dosing and limit the impact of tolerance development.

Production and characterization of antibodies specific for domains of human IgM.

A method of preparing antibodies against c mu 3 and c mu 4 domains of human IgM is described. c mu 3- and c mu 4-binding antibody fractions were isolated by affinity chromatography from IgG fractions of antisera raised against Fc5 mu and Fc mu' fragments. c mu 3 and c mu 4 fragments had been prepared from human IgM kappa (Key) by hot trypsin digestion. Haemagglutination inhibition tests showed that the c mu 4-binding fraction only reacted with c mu 4 fragments. The c mu 3-binding fraction reacted with c mu 3 fragments but showed a minor reaction with c mu 4 fragments. Immunization with Fc mu' fragments predominantly yielded antibodies against the c mu 3 domain, whereas immunization with Fc5 mu fragments yielded antibodies more directed against the c mu 4 domain. Immunization with isolated c mu 4 fragments led to the production of antibodies which reacted with the isolated c mu 4 domain but not with the c mu 4 domain within the larger structures of Fc mu' or Fc5 mu fragments.

Adaptation and overtraining in horses subjected to increasing training loads.

To evaluate markers for overtraining, seven male race horses were subjected to 272 days of training consisting of daily exercise bouts of either endurance running (heart rate 140/min) or interval training (maximal heart rate), both increasing in duration and intensity. An incremental exercise test was held every 4 wk, and from day 187 it was held every 2 wk. Muscle glycogen, muscle lactate, energy-rich phosphates, adrenal response to adrenocorticotropic hormone, plasma and red blood cell volumes, and a number of blood chemical variables were measured. The horses showed symptoms of weight loss, irritability, and an inability to complete the training after the intensity of the endurance exercise was increased. Test performance was not decreased. The adrenal response to adrenocorticotropic hormone was not changed during overtraining. The decline in muscle ATP concentration during maximal exercise was less during the period of staleness, whereas plasma volume, red blood cell volume, and blood chemical variables were unchanged. It was concluded that as long as exhaustive training is alternated by light exercise, overtraining is unlikely to occur. Furthermore, no single parameter can be used to detect early overtraining.

Stability measurements of antisense oligonucleotides by capillary gel electrophoresis.

The approach of using antisense oligonucleotides as potential drugs is based on hybridization of a short chemically-modified oligonucleotide with complementary cellular DNA or RNA sequences. A critical question is the stability of chemically modified antisense oligonucleotides in cellular environments. In a model system, resistance against various nucleases was evaluated by capillary gel electrophoresis (CGE). For some of the samples, matrix assisted laser desorption and ionization mass spectrometry (MALDI-MS) was used as an additional analytical tool to perform stability measurements. Using CGE, the enzymatic degradation of single nucleotides from the oligomer can be followed after different incubation times. 10% T polyacrylamide gels give baseline resolution for oligonucleotides ranging between 5 and 30 bases in length. The kinetic influence of a specific nuclease concentration and the antisense oligonucleotide structure on the cleavage reaction are discussed. Also, a simple desalting method to improve the injection efficiency and sensitivity of the method are described. Examples of measurements of chemically modified antisense 19-mers are presented.

Effects of acute normovolaemic haemodilution and partial exchange transfusion on blood product utilization, haemostasis and haemodynamics in surgery of the thoracoabdominal aorta. A cohort study in consecutive patients.

BACKGROUND: This paper outlines the technique of acute normovolaemic haemodilution with partial exchange transfusion (ANHPET) in surgery of the thoracic and thoracoabdominal aorta. Perioperative coagulation parameters and patterns of blood product utilization observed with this technique are described and compared with results for historical controls treated without ANHPET. METHODS: During thoracoabdominal aneurysm repair, acute normovolaemic haemodilution with partial exchange transfusion (ANHPET) was used to withdraw of up to 3 L of blood. This was returned to the patient at the end of the reconstruction. Albumin 5% and stored packed red cells (PRC) were used for replacement. Seven patients underwent surgery with ANHPET, and fifteen without. Univariate and multivariate analysis of variance was used to examine differences between these groups. RESULTS: No differences were observed between the two groups for estimated blood loss, PRC transfused, and postoperative haemoglobin concentration. The ANHPET group received fewer platelets (8 vs 22 units, p = 0.0004), cryoprecipitate (0 vs 13 units, p = 0.02), and desmopressin or epsilon-aminocaproic acid (0 of 7 vs 4 of 15 patients, p = 0.04). FFP use was not significantly different (11 vs 17 units). Postoperatively, PTT values were less prolonged (26 vs 34 sec, p = 0.05) and platelet concentration higher (218 vs 169 x 109/L, p = 0.01) in the ANHPET group. A significant reduction in the total of blood products transfused was observed in the ANHPET group (30 vs 68 units, p = 0.003). Control of hypertension was facilitated by phlebotomy so that nitroglycerine was necessary in low doses only (0.25-1.0 microgram/kg/min). CONCLUSIONS: ANHPET reduced blood product transfusion, improved postoperative haemostatic parameters and simplified the management of cross-clamping hypertension.

Perfusion of the subarachnoid space in cadavers: a technique applicable for prevention of paraplegia in surgery of the thoracic aorta.

BACKGROUND: No safe technique of subarachnoid perfusion during thoracoabdominal aneurysm surgery has been described. We tested the hypothesis that in cold cadavers, perfusion of the subarachnoid space at the lumbar level with warm solution is feasible and increases the temperature at the thoracic level without an increase in cerebrospinal fluid (CSF) pressure. METHODS: Six cadavers were used. A 5 Fr silastic catheter in the subarachnoid space between the second and third lumbar vertebra (L2-3) was used as an inflow and a 16-gauge catheter at L4-5 as an outflow. Normal saline at 38 degrees C was infused at 999 mL/h. Temperatures of inflow and outflow, of the thoracic subarachnoid space (T8), and of the cisterna magna, were recorded. CSF pressures were measured from the outflow catheter. RESULTS: Outflow temperature was 9+/-1 degrees C at 10 minutes. At 15 minutes it was 27+/-4 degrees C, and thoracic subarachnoid temperatures was 22+/-5 degrees C. There was no statistical difference between the temperatures recorded at 10 and 15 minutes. The temperature of the cisterna magna was 8.5+/-1.2 degrees C at 15 minutes, significantly higher than the baseline (p=0.01), but lower than that at the T8 level (p=0.0001). CSF pressures during the experiment did not changed significantly from baseline and remained below 10 cm H20. CONCLUSIONS: The technique described is simple to implement, and effective in changing the temperature of the subarachnoid space at the thoracic level. Whether spinal cord cooling by this technique safely reduces the risk of paraplegia remains to be established in an animal model.

Analgesic effect of interscalene block using low-dose bupivacaine for outpatient arthroscopic shoulder surgery.

BACKGROUND AND OBJECTIVES: Although interscalene brachial plexus block (ISBPB) is often used to provide anesthesia for arthroscopic shoulder surgery, its selective analgesic effect, provided by low-dose local anesthetic, has not been studied. We hypothesized that ISBPB using a low volume and low concentration of bupivacaine can provide effective postoperative analgesia for shoulder surgery without producing significant sensory or motor block elsewhere. METHODS: In this double-blind study, 30 outpatients scheduled to undergo shoulder arthroscopy were randomly assigned to receive either an ISBPB with 10 mL 0.125% bupivacaine with epinephrine 1:400,000 (n = 15) or 10 mL of normal saline (n = 15). The block was performed preoperative, prior to a standardized general anesthetic. Postoperative pain scores, imorphine and oral analgesic consumption, recovery profile, and patient satisfaction were recorded. RESULTS: In the ISBPB group, verbal analog pain scores within 120 minutes after surgery were lower, morphine consumption in the postanesthesia care unit was significantly lower (2.7+/-2.6 mg vs 9.5+/-5.2 mg), the time to postoperative administration of the first systemic or oral analgesic was significantly longer (141+/-182 minutes vs 13+/-10 minutes), the degree of motor and sensory block 120 minutes after surgery was minimal, time to reach hospital discharge criteria was earlier, and patient satisfaction with postoperative analgesia at 24-hour follow-up was greater. Thirty-three percent of the patients receiving ISBPB did not require any analgesic prior to hospital discharge. CONCLUSIONS: Interscalene brachial plexus block with low-dose bupivacaine is a useful and selective analgesic technique for outpatient shoulder arthroscopic surgery.

Acute normovolemic hemodilution (ANH) in surgery of the thoraco-abdominal aorta. A cohort study to evaluate coagulation parameters and blood products utilization.

OBJECTIVE: To assess whether a modified technique of acute normovolemic hemodilution (ANH) reduces the utilization of blood products and donor exposures, and/or improves hemostasis in surgery of the thoracoabdominal aorta. EXPERIMENTAL DESIGN: cohort study comparing fifteen control patients and seven treated with the adjunct of ANH. Mean follow-up 23 (SD=15.4) months. SETTING: community hospital acting as a referral centre for vascular diseases. Patients' selection: Thirty patients between 1990 and 1995 were entered into the study, eight were excluded because of rupture. INTERVENTIONS: the ANH technique used the withdrawal of up to 3000 ml blood during the time between induction of anesthesia and clamping of the thoracic aorta. Colloids were preferentially used for replacement together with up to three units of packed red blood cells (PRC). The autologous blood was retransfused during the final phases of the procedure. MEASURES: Parameters measured included pre- and postoperative PTT, INR, and platelets; the quantity of stored blood products and total donor exposures. RESULTS: Blood losses, PRC transfused, and postoperative hemoglobin concentration were not statistically different in the two groups. Repeated measures Analysis of variance on coagulation parameters showed lower PTT values (F1,20=4.2, p=0.05) and higher platelet concentration (F1,20=8.2, p=0.01) after surgery in the ANH group. In the latter, the reduction in fresh frozen plasma (FFP) utilization did not reach statistical significance (T19.5=1.79, p=0.08). This group, however, required fewer transfusions of platelets (T20=4.27, p=0.0004), and cryoprecipitate (T20=2.52, p=0.02), and no coagulation adjuncts (dDAVP, epsilon-aminocaproic acid), (Fisher's test=0.04). Total donor exposures was also significantly lower in the ANH group (T20=3.28, p=0.003). CONCLUSIONS: The ANH technique reduces homologous transfusions and donor exposures, and has a beneficial effect on hemostasis. Moreover, the technique may be useful in the management of cross clamping hypertension.

Predictive value of foal kinematics for the locomotor performance of adult horses.

The gait of 24 horses was recorded on a treadmill when they were trotting at 4 m sec-1, first when they were four months old and again when they were 26 months. The data recorded at four months were used to predict the locomotion of the adult horses, and the predictions were assessed against the data recorded at 26 months. The locomotion of the foals and the adults appeared to be closely related, when the differences in segment length and joint angles due to growth were taken into account. The duration of swing, the total range of protraction and retraction, and the maximum tarsal flexion could be used to predict adult locomotion, because they correlated very well between the foals and adults. The durations of stance and stride in the foals had to be linearly and dynamically scaled to the height at the withers to become predictive for the adult values. The duration of swing, and the total range of protraction and retraction and the maximum tarsal flexion are also indicators of the quality of gait and as a result studies of foal kinematics can be used objectively to predict the locomotor performance of adult horses.

How the horse moves: 1. Significance of graphical representations of equine forelimb kinematics.

The kinematics of 24 two-year-old Dutch Warmblood horses were recorded at the trot (4 m/s) on a high-speed treadmill to study the coordination of joints within the equine forelimb. Joint angle-time, angle-angle, stick, and marker diagrams were used to show forelimb motion graphically. Because the kinematic data referred to the joint angles of the horse standing squarely and were time-standardised to the duration of the stride cycle, mean joint curves could be calculated for the total group. The motion of each segment in the equine forelimb during a complete stride is described and its function in intralimb coordination evaluated. It appeared that the rotation of the scapula and the cranio-caudal movement of the distal forelimb are synchronous and pendular. The carpal joint rapidly snaps into overextension at the beginning of the stance phase to enable the forelimb to work as a propulsive strut. The fetlock joint acts as an elastic spring, thereby conserving energy and, at the same time, absorbs oscillations generated by initial ground contact. Furthermore, the coordination between carpal and fetlock joints in the swing phase appears to be strongly influenced by inertia. Using the graphic tools evaluated in this paper, we were able to visualise the kinematics of the equine forelimb and relate these to specific functions of the forelimb in locomotion. This information can be used to select kinematic variables for clinical studies in which equine forelimb function has to be described and quantified.

How the horse moves: 2. Significance of graphical representations of equine hind limb kinematics.

Kinematic data of the equine hind limb are presented graphically and related to functional aspects of the hind limb in locomotion. The trot of 24 two-year-old Dutch Warmblood horses was recorded at 4 m/s on a high-speed treadmill using kinematic analysis equipment. Joint angle-time, angle-angle, stick and marker diagrams were used to present graphically the data following standardised procedures. As the kinematic data were expressed with reference to the joint angles of the horse standing squarely and were time-standardised to the duration of the stride cycle, mean joint curves for the total group could be calculated and therefore describe the function of the different segments of the equine hind limb. The motion of the hind limb in the sagittal plane appeared to be pendular around a rotation point in the acetabulum. During the stance phase the extension of the fetlock joint and stance flexion of the stifle, tarsal and coffin joints illustrate the shock absorption of the hind limb. In the swing phase the reciprocal apparatus, which forms the coupling mechanism between stifle and tarsal joint, also influences the fetlock joint because synchronous flexion and extension between these 3 joints were demonstrated. By graphically presenting hind limb motion we were able to illustrate the relation between kinematics and function. This graphic analysis can be used in clinical studies involving quantification of equine hind limb coordination in the sagittal plane.

Kinematic detection of superior gait quality in young trotting warmbloods.

This study was conducted to identify objective criteria to select young horses with a good gait, which is a prerequisite for good performance in adult horses. The trot of 24 26-month-old Dutch Warmbloods, led on a loose shank, was subjectively scored by a judge and objectively assessed on a treadmill by using kinematic analysis equipment. It appeared that forelimb and hind limb stride and swing duration, scapula rotation, forelimb maximal fetlock extension, forelimb maximal retraction, hind limb maximal protraction, maximal stifle flexion, and maximal tarsal flexion significantly correlated with a generally accepted gait score in which length, suppleness, and strength are judged. Moreover, the ranking of the individual horses on the basis of gait quality according to their objectively measured kinematic variables was similar to the subjective ranking given by the judge. Thus, a complete picture was obtained of the variables in equine locomotion that determine the quality of the trot in warmbloods.

The effect of toe weights on linear and temporal stride characteristics of standardbred trotters.

Toe weights are applied to influence the stride characteristics of trotters. The quantitative effect of 88-g toe weights on the stride characteristics of Standardbred trotters was evaluated in a kinematic study using a CODA-3 analysis system. Six trotters were studied at a speed of 11 m/s on a treadmill. Temporal gait variables, joint angles, and the trajectories of the forelimb hoof were calculated. The stride patterns of the individual trotters were assessed by a judge and compared to the CODA-output. Those trotters with poor flexion of the carpal joint during the swing phase or with insufficient knee action responded with better carpal flexion and more knee action when toe weights were attached. No effect of toe weights on the protraction of the forelimb could be demonstrated. Stride length, stride duration, and the relative duration of the stance and swing phase as a percentage of the stride did not respond to toe weights. It is concluded that toe weights can be useful in Standardbred trotters, but their effect depends on the individual gait pattern.

Interference of maternal antibodies with the immune response of foals after vaccination against equine influenza.

The purpose of the study was twofold. First, using two groups of 22 foals each, we investigated the extent to which maternal antibodies interfere with the humoral response against equine influenza. The foals were born to mares that had been vaccinated twice yearly against influenza since 1982. Foals of group I were vaccinated three times at early ages (12, 16, and 32 weeks of age), and foals of group II were likewise vaccinated but a later ages (24, 28, and 44 weeks of age). After the first and second vaccinations, neither group showed an increase in antibodies that inhibit haemagglutination. Group II foals, however, had a significantly stronger antibody response against nucleoprotein after the second vaccination than the foals of group I. After the third vaccination, group II foals had a significantly stronger and longer lasting antibody response against haemagglutinin than the foals of group I. However, the antibody response to nucleoprotein was comparable in both groups. Second, the foals of group II were studied to determine the persistence of maternal antibodies directed against a common nucleoprotein and the haemagglutinin of two strains of equine influenza A virus. Biological half-lives of 39, 32, and 33 days were calculated for maternal antibodies directed against haemagglutinin of strains H7N7 Prague and H3N8 Miami, and against the nucleoprotein respectively. Maternal antibody titres at the time of vaccination were closely related to the degree of interference with the immune response. Because even small amounts of maternal antibodies interfered with the efficacy of vaccination, we conclude that foals born to mares vaccinated more than once yearly against influenza virus should not be vaccinated before 24 weeks of age.

[Testing of a deworming scheme for horses]. / Het testen van een ontwormingsschema voor paarden.

In 1983 and 1984 the effect of a deworming scheme, in which horses were treated at turn out and 4 and 8 weeks later, on the egg output, larval differentiation, weight gain, herbage infestation and in 1984, the percentages of some serum proteins were tested. In 1983 the experiment was done with 42 mares, 54 two year old male horses and 42 male yearlings, kept in groups with permanent or rotational grazing. In 1984 only 90 male yearlings were investigated. In 1983 albendazole and ivermectin were used, 1984 ivermectin. The results of the faecal examinations showed that after ivermectin treatment the number of eggs per gram faeces (EPG) remained zero or very low for a longer time. In 1983 an increase was seen during August. In 1984 the increase was observed at the end of August/beginning of September. Treatment with albendazole gave a less efficient suppression of egg output, resulting in a sharp EPG-increase at the end of July/beginning of August. After first treatment either with ivermectin or albendazole, no larvae of great Strongyles were seen. The results of the herbage infestation on the paddocks were according to the EPGs of the horses that grazed the paddocks some time earlier. Infestation was highest in late summer and autumn, lowest in early and mid summer. No significant differences in weight gain were observed between the groups. The percentage of beta 1 + 2-globulin was highest at turn out. After first treatment it decreased, but remained stable thereafter during the season, irrespective of the reinfection in autumn. Post-mortem results of four tracers in 1984 varied from ca. 275,000-2,000,000 small Strongyles. The conclusion was drawn that under the present conditions the system was not satisfactory to prevent a reasonable worm infestation in late summer/autumn. The following advice was given: treatment of horses at least 48 hours before turn out, deworming each four weeks up till July, treatment in September and in November (also against Gasterophilus).