Global Therapeutic Research

Portage, MI, United States

Global Therapeutic Research

Portage, MI, United States
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Clawson M.L.,U.S. Department of Agriculture | Murray R.W.,Global Therapeutic Research
Animal Health Research Reviews | Year: 2014

Bovine respiratory disease complex (BRDC) is a major animal health and economic issue that affects cattle industries worldwide. Within the USA, the beef cattle industry loses up to an estimated 1 billion dollars a year due to BRDC. There are many contributors to BRDC, including environmental stressors and viral and/or bacterial infections. One species of bacteria in particular, Mannheimia haemolytica, is recognized as the major cause of severe fibrinonecrotic pneumonia in cattle. M. haemolytica is an opportunistic pathogen that normally populates the upper respiratory tract of cattle, and invades the lower respiratory tract in stressed and/or virally infected cattle by mechanisms that are not completely understood. However, not all M. haemolytica appear to be equally pathogenic to cattle. Thus, a test could be developed to distinguish M. haemolytica genetic subtypes by their propensity to cause respiratory disease, allowing isolation and/or treatment of cattle harboring strains with an increased propensity to cause disease. To that end, the genomes of over 300 M. haemolytica strains are being sequenced. Copyright © Cambridge University Press 2014 This is a work of the U.S. Government and is not subject to copyright protection in the United States..


Rong S.,Global Biologics Research | Lowery D.,Global Therapeutic Research | Lowery D.,Novartis | Floyd-Hawkins K.,Global Development and Operations | King V.,Global Development and Operations
Virus Research | Year: 2014

Highly virulent, systemic strains of Feline calicivirus (vs FCV) have been described in recent years. These vs FCV isolates cause severe edema, cutaneous ulcers, lameness and other upper respiratory and oral clinical signs typically associated with FCV infection in cats. Vs FCV isolates can cause high mortality even in cats vaccinated with currently available commercial vaccines. This study reports identification and characterization of an avirulent FCV strain (FCV 21). This strain offers a broader serum cross-neutralization profile in comparison with the commonly used vaccine strain (FCV F9), as tested with two separate viral panels of FCV isolates. The first viral panel consists of 45 FCV strains isolated around 1993. The second viral panel consists of 26 FCV strains with most isolated around 2003. The potential of using this strain as a vaccine, in a 3-way (FCV. +. FHV. +. FPV) or 4-way (FCV. +. FHV. +. FPV. +. FCp) format, was tested by using a highly virulent vs FCV strain (FCV-33585) as a challenge virus. The mortality induced by this vs FCV in unvaccinated control cats was 78% (7 out of 9 cats). The mortality decreased to 44% (4 out of 9 cats) in cats vaccinated with a 4-way vaccine containing FCV F9. However, when this novel FCV vaccine strain (FCV 21) was used, either in combination with FCV F9 or by itself, the mortality decreased to 0% (0 out of 10 cats). The 3-way vaccine (FCV. +. FHV. +. FPV) that contained both FCV 21 and FCV F9 also had mortality of 0% (0 out of 10 cats). The clinical scores, as calculated taking into consideration the frequency and severity of various clinical signs, correlated with mortality data. The results suggested this FCV vaccine has the potential to be broadly protective against newly emergent FCV isolates, including complete protection against challenge with a highly virulent vs FCV 33585. © 2014 Elsevier B.V.


Yuan Y.,Global Therapeutic Research | Dego O.K.,University of Tennessee at Knoxville | Chen X.,University of Tennessee at Knoxville | Abadin E.,Global Therapeutic Research | And 5 more authors.
Journal of Dairy Science | Year: 2014

The objective was to identify and sequence the sua gene (GenBank no. DQ232760; http://www.ncbi.nlm.nih.gov/genbank/) and detect Streptococcus uberis adhesion molecule (SUAM) expression by Western blot using serum from naturally S. uberis-infected cows in strains of S. uberis isolated in milk from cows with mastitis from geographically diverse areas of the world. All strains evaluated yielded a 4.4-kb sua-containing PCR fragment that was subsequently sequenced. Deduced SUAM AA sequences from those S. uberis strains evaluated shared >97% identity. The pepSUAM sequence located at the N terminus of SUAM was >99% identical among strains of S. uberis. Streptococcus uberis adhesion molecule expression was detected in all strains of S. uberis tested. These results suggest that sua is ubiquitous among strains of S. uberis isolated from diverse geographic locations and that SUAM is immunogenic. © 2014 American Dairy Science Association.


PubMed | Global Therapeutic Research
Type: Comparative Study | Journal: Veterinary immunology and immunopathology | Year: 2013

To date, very little is known about the functional characteristics of the four published canine IgG subclasses. It is not clear how each subclass engages the immune system via complement-dependent cytotoxicity (CDC) or antibody-dependent cell-mediated cytotoxicity (ADCC), or how long each antibody may last in serum. Such information is critical for understanding canine immunology and for the discovery of canine therapeutic monoclonal antibodies. Through both in vitro and ex vivo experiments to evaluate canine Fcs for effector function, complement binding, FcRn binding, and ADCC, we are now able to categorize canine subclasses by function. The subclasses share functional properties with the four human IgG subclasses and are reported herein with their function-based human analog. Canine Fc fusions, canine chimeras, and caninized antibodies were characterized. Canine subclasses A and D appear effector-function negative while subclasses B and C bind canine Fc gamma receptors and are positive for ADCC. All canine subclasses bind the neonatal Fc receptor except subclass C. By understanding canine IgGs in this way, we can apply what is known of human immunology toward translational and veterinary medicine. Thus, this body of work lays the foundation for evaluating canine IgG subclasses for therapeutic antibody development and builds upon the fundamental scholarship of canine immunology.


PubMed | University of Tennessee at Knoxville and Global Therapeutic Research
Type: Journal Article | Journal: Journal of dairy science | Year: 2014

The objective was to identify and sequence the sua gene (GenBank no. DQ232760; http://www.ncbi.nlm.nih.gov/genbank/) and detect Streptococcus uberis adhesion molecule (SUAM) expression by Western blot using serum from naturally S. uberis-infected cows in strains of S. uberis isolated in milk from cows with mastitis from geographically diverse areas of the world. All strains evaluated yielded a 4.4-kb sua-containing PCR fragment that was subsequently sequenced. Deduced SUAM AA sequences from those S. uberis strains evaluated shared >97% identity. The pepSUAM sequence located at the N terminus of SUAM was >99% identical among strains of S. uberis. Streptococcus uberis adhesion molecule expression was detected in all strains of S. uberis tested. These results suggest that sua is ubiquitous among strains of S. uberis isolated from diverse geographic locations and that SUAM is immunogenic.


PubMed | U.S. Department of Agriculture and Global Therapeutic Research
Type: Journal Article | Journal: Animal health research reviews | Year: 2014

Bovine respiratory disease complex (BRDC) is a major animal health and economic issue that affects cattle industries worldwide. Within the USA, the beef cattle industry loses up to an estimated 1 billion dollars a year due to BRDC. There are many contributors to BRDC, including environmental stressors and viral and/or bacterial infections. One species of bacteria in particular, Mannheimia haemolytica, is recognized as the major cause of severe fibrinonecrotic pneumonia in cattle. M. haemolytica is an opportunistic pathogen that normally populates the upper respiratory tract of cattle, and invades the lower respiratory tract in stressed and/or virally infected cattle by mechanisms that are not completely understood. However, not all M. haemolytica appear to be equally pathogenic to cattle. Thus, a test could be developed to distinguish M. haemolytica genetic subtypes by their propensity to cause respiratory disease, allowing isolation and/or treatment of cattle harboring strains with an increased propensity to cause disease. To that end, the genomes of over 300 M. haemolytica strains are being sequenced.

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