RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to impose a serious burden on health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of the virus is ongoing. One of the mechanisms by which neutralizing antibodies (NAbs) block virus entry into cells encompasses interaction inhibition between the cell surface receptor angiotensin-converting enzyme 2 (ACE2) and the spike (S) protein of SARS-CoV-2. SARS-CoV-2-specific NAb development can be induced in the blood of cattle. Pregnant cows produce NAbs upon immunization, and antibodies move into the colostrum immediately before calving. Here, we immunized cows with SARS-CoV-2 S1 receptor binding domain (RBD) protein in proper adjuvant solutions, followed by one boost with SARS-CoV-2 trimeric S protein and purified immunoglobulins from colostrum. We demonstrate that this preparation indeed blocks the interaction between the trimeric S protein and ACE2 in different in vitro assays. Moreover, we describe the formulation of purified immunoglobulin preparation into a nasal spray. When administered to human subjects, the formulation persisted on the nasal mucosa for at least 4 hours, as determined by a clinical study. Therefore, we are presenting a solution that shows great potential to serve as a prophylactic agent against SARS-CoV-2 infection as an additional measure to vaccination and wearing masks. Moreover, our technology allows for rapid and versatile adaptation for preparing prophylactic treatments against other diseases using the defined characteristics of antibody movement into the colostrum.
Assuntos
COVID-19 , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2 , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Bovinos , Colostro/metabolismo , Feminino , Humanos , Gravidez , Glicoproteína da Espícula de CoronavírusRESUMO
OBJECTIVE: The butorphanol-azaperone-medetomidine fixed-dose combination (BAM, respectively, 30-12-12 mg mL-1) with subsequent antagonism by naltrexone-atipamezole was evaluated for reversible immobilization of captive cheetahs (Acinonyx jubatus). STUDY DESIGN: Prospective, clinical trial. ANIMALS: Twelve cheetahs (six males and six females, weighing 37-57 kg) housed in enclosures, were immobilized at Hoedspruit Endangered Species Centre in the Republic of South Africa. METHODS: BAM volume dose rate was 0.009-0.014 mL kg-1 (mean ± standard deviation 0.010 ± 0.001 mL kg-1). Total dose in all animals was 0.5 mL. The actual doses were as follows: butorphanol (0.29 ± 0.04 mg kg-1), azaperone (0.12 ± 0.01 mg kg-1) and medetomidine (0.12 ± 0.01 mg kg-1). Physiologic variables and quality of immobilization were recorded every 5 minutes beginning at 15-20 minutes after darting. Arterial blood samples were collected three times at 20, 30 and 40 minutes after darting from all animals for analysis of blood oxygenation and acid-base status. RESULTS: The inductions were calm and smooth and mean induction time was 4.0 ± 1.1 minutes. Heart rate (50 ± 9 beats minute-1) and respiratory frequency (20 ± 3 breaths minute-1) were stable throughout immobilization. The recovery time after reversing with naltrexone and atipamezole was 9.1 ± 3.6 minutes. CONCLUSIONS: and clinical relevance BAM proved to be a reliable and cardiovascular stable drug combination for immobilization of cheetahs.
Assuntos
Acinonyx/fisiologia , Anestesia/veterinária , Azaperona/farmacologia , Butorfanol/farmacologia , Hipnóticos e Sedativos/farmacologia , Imobilização/veterinária , Medetomidina/farmacologia , Anestésicos Combinados , Animais , Animais de Zoológico/fisiologia , Azaperona/administração & dosagem , Butorfanol/administração & dosagem , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Medetomidina/administração & dosagem , Estudos Prospectivos , Taxa Respiratória/efeitos dos fármacos , Resultado do TratamentoRESUMO
OBJECTIVE: The fixed-dose combination of butorphanol, azaperone and medetomidine (BAM; 30, 12 and 12 mg mL-1, respectively) with subsequent antagonism by naltrexone-atipamezole was evaluated for reversible immobilization of captive blesbok (Damaliscus pygargus phillipsi). STUDY DESIGN: Prospective, clinical trial. ANIMALS: Sixteen blesbok (four males and twelve females), weighing 52.5-71.0 kg, were immobilized in South Africa. METHODS: The total dose of BAM ranged from 0.5 to 0.7 mL for females and 0.7 to 0.9 mL for males. In seven animals chosen randomly, 8000 units of hyaluronidase was added to the dart. Physiologic variables were recorded every 5 minutes beginning at 10-20 minutes after darting. Arterial blood samples were collected three times at 20, 30 and 40 minutes after darting for analysis of blood acid-base status. RESULTS: The mean administered doses of BAM were as follows: butorphanol (0.34 ± 0.08 mg kg-1), azaperone (0.14 ± 0.03 mg kg-1) and medetomidine (0.14 ± 0.03 mg kg-1). The inductions were calm and smooth. The mean induction time was 9.6 ± 3.2 minutes with just BAM and 5.1 ± 0.8 minutes with BAM and hyaluronidase combination. Heart rate (45 ± 6 beats minute-1) and respiratory frequency (38 ± 4 breaths minute-1) were stable throughout immobilization. The mean arterial blood pressure for all animals was stable but elevated (137 ± 7 mmHg). Rectal temperature slightly increased over time but remained within an acceptable range. The recovery time after administering naltrexone and atipamezole was 4.8 ± 0.7 minutes. CONCLUSION AND CLINICAL RELEVANCE: The BAM combination proved to be reliable and effective in blesbok.
Assuntos
Antílopes , Azaperona/administração & dosagem , Butorfanol/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Imobilização/veterinária , Medetomidina/administração & dosagem , Anestésicos Combinados/administração & dosagem , Animais , Animais Selvagens , Feminino , Imobilização/métodos , Injeções Intramusculares/métodos , Injeções Intramusculares/veterinária , MasculinoRESUMO
EFSA and EMA have jointly reviewed measures taken in the EU to reduce the need for and use of antimicrobials in food-producing animals, and the resultant impacts on antimicrobial resistance (AMR). Reduction strategies have been implemented successfully in some Member States. Such strategies include national reduction targets, benchmarking of antimicrobial use, controls on prescribing and restrictions on use of specific critically important antimicrobials, together with improvements to animal husbandry and disease prevention and control measures. Due to the multiplicity of factors contributing to AMR, the impact of any single measure is difficult to quantify, although there is evidence of an association between reduction in antimicrobial use and reduced AMR. To minimise antimicrobial use, a multifaceted integrated approach should be implemented, adapted to local circumstances. Recommended options (non-prioritised) include: development of national strategies; harmonised systems for monitoring antimicrobial use and AMR development; establishing national targets for antimicrobial use reduction; use of on-farm health plans; increasing the responsibility of veterinarians for antimicrobial prescribing; training, education and raising public awareness; increasing the availability of rapid and reliable diagnostics; improving husbandry and management procedures for disease prevention and control; rethinking livestock production systems to reduce inherent disease risk. A limited number of studies provide robust evidence of alternatives to antimicrobials that positively influence health parameters. Possible alternatives include probiotics and prebiotics, competitive exclusion, bacteriophages, immunomodulators, organic acids and teat sealants. Development of a legislative framework that permits the use of specific products as alternatives should be considered. Further research to evaluate the potential of alternative farming systems on reducing AMR is also recommended. Animals suffering from bacterial infections should only be treated with antimicrobials based on veterinary diagnosis and prescription. Options should be reviewed to phase out most preventive use of antimicrobials and to reduce and refine metaphylaxis by applying recognised alternative measures.