Impacts of polyclonal antibody preparations from avian origin as a feed additive to beef cattle: Immune responses during the step-up transition diets

This study investigated the effects of feeding an avian-derived polyclonal antibody preparation (PAP; CAMAS, Inc.) against Streptococcus bovis, Fusobacterium necrophorum, and lipopolysaccharides (40, 35, and 25% of the preparation, respectively) on immune responses [haptoglobin (Hp), serum amyloid A (SAA), rectal temperature (RT), leukocyte counts, and expression of cell adhesion molecules cluster of differentiation (CD) CD11b, CD14, and CD62L] of beef steers during a 21-d step-up adaptation to a high-grain diet. Eight ruminally cannulated Angus crossbred beef steers (658 ± 79 kg of BW) were assigned in a cross-over design and transitioned from a diet containing bermudagrass hay [Cynodon dactylon (L.) Pers.] ad libitum plus 0.45 kg/d of molasses with 0 (CON) or 3 g of PAP (PAP) to a high-grain diet. Transition consisted of three 7-d steps of increased inclusion of cracked corn (35, 60, and 82% of the diet dry matter for STEP1, STEP2, and STEP3, respectively). On each transition day and 7 d after STEP3 (STEP3-7d), RT was obtained every 3 h for a total of 24 h, whereas blood was collected on d 0, 1, and 3, relative to diet transition. There were no effects of PAP inclusion in any of the blood parameters (P > 0.11). However, a tendency for day effect (P = 0.10) was observed for concentrations of Hp, which were greater on d 3 and 7 vs. d 0 relative to the second diet transition (STEP2). Plasma concentrations of SAA were greater on d 1, 3, and 7 compared to d 0 during STEP1 (P = 0.01), while during STEP2 and STEP3, SAA concentrations increased (P < 0.01) from d 0 to 3. During STEP2, PAP steers tended to have lower (P = 0.08) RT than CON steers. Neutrophil and monocyte counts were the least during STEP3 (P < 0.01), whereas expression of CD11b and CD62L was the least through forage feeding (P < 0.01). Concentration of starch in the diet was correlated to all the variables tested (P ≤ 0.01), except for the percentage of B cells (P = 0.22). Yet only ruminal pH, RT, monocyte, and neutrophil counts presented strong correlation coefficients. In conclusion, the step-up transition from forage to high-grain diets triggered systemic inflammation in beef steers as observed by increased plasma concentrations of haptoglobin, serum amyloid A, and expression on adhesion molecules in leukocytes. However, feeding polyclonal antibody preparations against Streptococcus bovis, Fusobacterium necrophorum, and lipopolysaccharide did not provide benefits to mitigate inflammation.

A Review of the Efficacy of FDA-Approved B. anthracis Anti-Toxin Agents When Combined with Antibiotic or Hemodynamic Support in Infection- or Toxin-Challenged Preclinical Models

Anti-toxin agents for severe B. anthracis infection will only be effective if they add to the benefit of the two mainstays of septic shock management, antibiotic therapy and titrated hemodynamic support. Both of these standard therapies could negate benefits related to anti-toxin treatment. At present, three anthrax anti-toxin antibody preparations have received US Food and Drug Administration (FDA) approval: Raxibacumab, Anthrax Immune Globulin Intravenous (AIGIV) and ETI-204. Each agent is directed at the protective antigen component of lethal and edema toxin. All three agents were compared to placebo in antibiotic-treated animal models of live B. anthracis infection, and Raxibacumab and AIGIV were compared to placebo when combined with standard hemodynamic support in a 96 h canine model of anthrax toxin-associated shock. However, only AIG has actually been administered to a group of infected patients, and this experience was not controlled and offers little insight into the efficacy of the agents. To provide a broader view of the potential effectiveness of these agents, this review examines the controlled preclinical experience either in antibiotic-treated B. anthracis models or in titrated hemodynamic-supported toxin-challenged canines. The strength and weaknesses of these preclinical experiences are discussed.

PSXII-6 Supplementation of Angus crossbred steers with avian-derived polyclonal antibody preparations against the ruminal methanogen Methanobrevibacter ruminantium M1 does not alter in vivo methane emissions

An experiment was conducted to evaluate the effect of supplementing twenty Angus crossbred steers with avian-derived polyclonal antibody preparations (PAP) against the ruminal methanogen Methanobrevibacter ruminantium M1 on in vivo methane production, using the sulfur hexafluoride (SF6) tracer technique (Johnson et al., 1994). Steers were fed chopped bermudagrass hay (BGH) ad libitum and 0.7 kg d-1 of corn gluten feed. The experiment followed a change-over design. Treatments were 1) supplementation of 3 mL d-1 of PAP against M. ruminantium M1 (PAP-M1), and 2) supplementation of 3 mL d-1 of a non-immunized egg product (CON). Individual BGH intake was recorded using an electronic radio-frequency monitoring system (GrowSafe System Ltd., Airdrie, Alberta, Canada). There was a 14-d adaptation period to the feeding regime, with no PAP supplementation, followed by an 18-d treatment period. Steers were dosed with brass permeation tubes with a known release rate of SF6 on d 7 of treatment period. Enteric methane emissions were sampled from d 13 to 18 of the treatment period, into N-rinsed pre-evacuated U-shaped polyvinyl chloride canisters (2 L) through a capillary tube. Methane emissions were averaged per animal within period. Data were analyzed as a change-over design using a model with fixed effects of order, period, and treatment and random effect of steer within order. Dry matter intake (DMI) was not different (P = 0.44) between treatments. Methane emissions, expressed as grams per day (P = 0.86), as grams per kilogram of DMI (P = 0.78), or in terms of methane emission factors (Ym, P = 0.78) were not different between PAP-M1 and CON treatments. Supplementation of steers with PAP against M. ruminantium M1 did not decrease enteric methane emissions. Based on preliminary ex situ trials, evaluation of different doses and combinations of PAP against other methanogenic species warrant further investigation.

184 President Oral Presentation Pick: Supplementation of Angus crossbred steers with avian-derived polyclonal antibody preparations against ruminal methanogenic Archaea alters ruminal fermentation and decreases ex situ methane production

An experiment was conducted to evaluate the effect of supplementing fourteen ruminally cannulated Angus crossbred steers with polyclonal antibody preparations (PAP) from avian origin against ruminal methanogens Methanobrevibacter gottschalkii Ho (PAP-Ho) and M. ruminantium M1 (PAP-M1). Steers were fed bermudagrass hay ad libitum and 2 kg d-1 of corn gluten feed. A randomized block design was used, with a 3 × 2 + 1 factorial arrangement, replicated in three periods. Factors were proportions of PAP against Ho and M1 in the mixture (100:0, 50:50, and 0:100 Ho:M1) and level of supplementation of each mixture (3 or 6 mL d-1). Control steers had no PAP supplementation. Steers were adapted to the feeding regimen for 14 d, with no PAP supplementation, followed by a 21-d treatment period. Ruminal fluid (RF) from each steer (experimental unit) was collected before PAP supplementation (h 0) and every 4 h (for a 24-h period) on d 0, 14, and 21 of treatment period for the determination of ruminal fermentation profile. In addition, RF collected at h 0 was individually mixed with McDougall’s Buffer (1:3 ratio) to inoculate serum bottles and polycarbonate tubes for the determination of methane production and in vitro fermentation profile. Treatment means were evaluated by preplanned, non-orthogonal, single-degree-of-freedom contrasts. There was no effect (P ≥ 0.48) of level of inclusion on ex situ methane production (ESMP). When PAP-M1 was used either alone or in combination with PAP-Ho, ESMP decreased (P ≤ 0.05) compared to control. Ex situ ruminal fermentation profile was not different (P ≥ 0.12) across treatments. In vivo molar proportion of propionate tended to be greater (P = 0.10) with supplementation of PAP-M1, alone or combined, compared with control. Polyclonal antibody preparations against ruminal methanogens have the potential to decrease enteric methane emissions.

123 Polyclonal antibody preparations from avian origin did not reduce plasmatic haptoglobin concentrations but increased ruminal NH3-N in beef steers during transition from forage to high-grain diets

This study investigated the effects of feeding an avian-derived polyclonal antibody preparation (PAP; CAMAS, Inc.) against Streptococcus bovis, Fusobacterium necrophorum, and lipopolysaccharides (40, 35, and 25% of the preparation, respectively) on plasmatic haptoglobin, ruminal short chain fatty acids (SCFA), and ammonia-N (NH3-N) concentrations of beef steers during a 21-d step-up adaptation to a high-grain diet. Eight ruminally cannulated Angus crossbred beef steers (658 ± 79 kg BW) were randomly assigned to treatments in a crossover design to be transitioned from a diet containing bermudagrass hay [Cynodon dactylon (L.) Pers.] plus 0.45 kg/d of molasses with 0 (CON) or 3 g/d of PAP (PAP) to a high-grain diet. Transition consisted of three 7-d steps of increased inclusion of cracked corn (35, 60, and 80% diet DM for STEP1, STEP2, and STEP3, respectively). On each transition d and 7 d after STEP3 (STEP3-7d), ruminal fluid samples were obtained every 3 h for 24 h. Blood samples were collected on d 0, 1, and 3 relative to each transition for haptoglobin determinations. Haptoglobin plasmatic concentrations increased (P = 0.03) on d 2 and 3 vs. d 1 during STEP2 and on STEP3 compared to STEP1 and STEP2 (P = 0.01). Steers receiving PAP had greater (P < 0.01) ruminal NH3-N concentration in STEP1; however, there were no effects of treatment on SCFA (P > 0.10). Total SCFA concentrations were affected by the step-up diets (P < 0.01); propionate concentration (Pro) was greater in STEP2 through STEP3-7d vs. STEP1 (P < 0.01), whereas acetate concentration (Ac) and Ac:Pro linearly decreased from STEP1 to STEP3-7d (P < 0.01). Feeding 3 g/d of polyclonal antibody preparations against Streptococcus bovis, Fusobacterium necrophorum, and lipopolysaccharides in a 21-d step-up adaptation to high-grain diets did not affect plasmatic haptoglobin or ruminal SCFA concentrations; however, it increased ruminal NH3-3 concentrations.

Monoclonal antibodies in the treatment of multiple sclerosis: from clinical research to practical application

Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating and neurodegenerative disease with a multifactorial etiology of development. MS in most cases has a wave-like course (periods of exacerbations and remissions), over time, the disease becomes progressive, which worsens the quality of life of patients. The drugs disease-modifying therapies (DMT) has been actively used in clinical practice for more than 30 years to prevent exacerbations and progression of MS. In patients with MS, in which the disease occurs with frequent exacerbations and signs of radiological activity of the demyelinating process, according to magnetic resonance imaging (MRI) of the brain and spinal cord, it is recommended to use monoclonal antibody preparations. The only drug registered for the treatment of primary progressive MS is ocrelizumab. In addition, ocrelizumab is indicated for patients with remitting and secondary progressive MS. Ocrelizumab is a humanized monoclonal antibody that selectively depletes a population of CD20+ B cells. The article presents data from clinical studies of OPERA I and OPERA II and describes a clinical case from the practice of a neurologist. Depletion of the B cell population is achieved by several mechanisms, including antibody-dependent cell-mediated phagocytosis, antibody-dependent T cell-mediated cytotoxicity, complement-dependent cytotoxicity, and apoptosis induction. The issues of efficacy and safety of ocrelizumab therapy in patients with MS are considered.

Use of monoclonal antibodies in patients with multiple sclerosis in the practice of a neurologist

Multiple sclerosis (MS) ranks first for prevalence among diseases affecting the CNS white matter with 2.5 million cases estimated globally. InRussia, the number of cases is about 200 thousand. MS in most cases has a wavy course (periods of exacerbations and remissions), over time the progression of disease worses the quality of life of patients. The “gold standard” at the beginning of MS is first-line drugs disease-modifying therapies (DMT). If they are ineffective, it is necessary to strengthen the effect on the immune processes and the patient is prescribed second-line drugs (escalation of therapy). There is a method of induction therapy, when high activity of MS is recommended to start with drugs that have a strong immunosuppressive effect with a possible subsequent transition to soft supportive treatment. In patients with frequent exacerbations and signs of radiological activity of the disease, according to magnetic resonance imaging (MRI) of the brain and spinal cord, monoclonal antibody preparations are effectively used. Except of escalation and induction, it is also used the method of immune system reconstruction, which leads to a decrease in autoagression in MS. This article discusses a clinical case of using a drug of monoclonal antibodies that selectively bind to CD 52 on the surface of lymphocytes. The issues of efficacy and safety of alemtuzumab therapy in patients with MS are considered.

416 Polyclonal antibody preparations from avian origin increase mean ruminal pH and reduce rectal temperature of beef steers during transition from forage to high-grain diets

This study investigated the effects of feeding an avian-derived polyclonal antibody preparation (PAP; CAMAS, Inc.) against Streptococcus bovis, Fusobacterium necrophorum, and lipopolysaccharides (40, 35, and 25% of the preparation, respectively) on dry matter intake (DMI), mean ruminal pH (pH), and rectal temperature (RT) of beef steers during a 21-d step-up adaptation to a high-grain diet. Eight ruminally cannulated Angus crossbred beef steers (658 ± 79 kg of BW) were randomly assigned in a crossover design to be transitioned from a diet containing bermudagrass hay [Cynodon dactylon (L.) Pers.] ad libitum plus 0.45 kg/d of molasses with 0 (CON) or 3 g of PAP (PAP) to a high-grain diet. Transition consisted of three 7-d steps of increased inclusion of cracked corn (35, 60, and 80% of the diet DM for STEP1, STEP2, and STEP3, respectively). On each transition d and 7 d after STEP3 (STEP3-7d), ruminal pH and RT were measured every 3 h for 24 h and feed intake was recorded daily throughout the study using the GrowSafe feed intake monitoring system. Feed intake was not influenced by PAP on transition days (P ≥ 0.44) or during the wk each transition diet was offered (P ≥ 0.57). However, DMI linearly decreased, whereas RT increased from STEP1 to STEP3 (P < 0.01). Steers receiving PAP in STEP2 had reduced RT (P = 0.05). Additionally, steers receiving PAP on STEP3 had greater ruminal pH (P = 0.03), nevertheless, pH was similar between treatments in STEP3-7d (P = 0.39). Feeding 3 g of polyclonal antibody preparations against Streptococcus bovis, Fusobacterium necrophorum, and lipopolysaccharides in a 21-d step-up adaptation to high-grain diets may stabilize ruminal pH and reduce rectal temperature of beef steers. Future studies should characterize the effects of PAP on immune response to elucidate potential modes of action of these feed additives.