Papers by Randall L. Levings
Animal Health Research Reviews, Jun 1, 2013
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Veterinary Microbiology, Nov 1, 1993
Each finished batch or serial of veterinary vaccine must be potency tested to assure the quality ... more Each finished batch or serial of veterinary vaccine must be potency tested to assure the quality of marketed product. The potency assay must be correlated to efficacy in the target species. Potency assays of nonreplicating vaccines have traditionally measured the immune response to the vaccine in host or laboratory animals by serology or protection from challenge. Such tests are expensive, time-consuming, and raise animal welfare concerns. As disease agent protective antigens are described, in vitro techniques for quantitating them can be applied to vaccine potency measurement. However, in many cases the immunological adjuvants critical to the efficacy of the biological interfere with in vitro antigen quantitation techniques. The development of techniques that remove or compensate for the effect of adjuvants on the assays, sham vaccines containing no antigen, reference preparations containing a proven protective immunogen dose, characterization of the immunological reactants, and appropriate design and data analysis have contributed to the development of rapid, reproducible, humane, and relatively inexpensive in vitro potency assays to be used in the evaluation of veterinary biologicals.
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PubMed, 1991
Bovine viral diarrhea virus (BVDV) infection is common in the bovine population. Infection in ute... more Bovine viral diarrhea virus (BVDV) infection is common in the bovine population. Infection in utero leads to virus and antibody contamination of the fetal bovine serum used in cell cultures. These contaminants can interfere with diagnosis of viral infection. The high frequency of virus and antibody detection in individual animal or small pool samples suggests that any large pool of unscreened sera will be contaminated. Infection of cell cultures with BVDV can lead to interference with the growth of other viruses. Vaccine produced on contaminated cells may in turn be contaminated, leading to seroconversion or disease in the vaccine. The safety, purity, and efficacy of viral vaccines require BVDV testing of ingredients, cell substrates and final product. Methods for detection of BVDV in nutrient serum, cell cultures, seed viruses, and viral vaccines, and the frequency of their detection at the National Veterinary Services Laboratories are discussed.
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Journal of Veterinary Diagnostic Investigation, Jul 1, 1994
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PubMed, 1999
Infection with bovine viral diarrhoea virus (BVDV) and other viruses is frequent in the bovine po... more Infection with bovine viral diarrhoea virus (BVDV) and other viruses is frequent in the bovine population. In utero infection leads to virus and antibody contamination of foetal and other serum used in cell culture production. The use of contaminated cells for vaccine production may result in contaminated vaccines, which may lead to seroconversion or disease in the vaccinated animal. Contaminated serum or cell cultures may also interfere with the diagnosis of viral infections. Methods for the detection of BVDV and other viruses in serum, cell cultures, seed viruses and vaccines at the CVB-L, and the frequency of detection are described. Reasons for continued use of serum in cell culture production, and the risks of using serum, are discussed.
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PubMed, Jun 1, 1991
We report here genetic recombination between 2 USDA-licensed vaccine strains of pseudorabies viru... more We report here genetic recombination between 2 USDA-licensed vaccine strains of pseudorabies virus co-inoculated into swine. The vaccine strains, one of which was a conventionally attenuated strain and the other, a genetically engineered deleted strain containing a negative immunologic marker, had complementary genomes. Co-inoculation resulted in the creation of novel strains of pseudorabies virus containing negative immunologic markers with restored virulence genes. Plaque-purified recombinant progeny viruses were found in 2 litters of pigs in which both strains were co-inoculated IM, a litter in which both strains were co-inoculated oronasally, and a litter in which the conventionally attenuated strain was inoculated oronasally and the genetically engineered strain was inoculated IM. Recombinant phenotypes and recombinant restriction fragment patterns were observed. The creation, spread, and potential misdiagnosis of these types of recombinant strains could disrupt control and eradication programs that are based on the serologic identification of swine infected with potentially virulent strains of pseudorabies virus.
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Veterinary Microbiology, Aug 1, 1984
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Veterinary Immunology and Immunopathology, Apr 1, 2015
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Animal Health Research Reviews, Jun 1, 2013
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Current applications of cell culture engineering, 1998
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Journal of Immunology, May 1, 2014
The cDNA of heterohybridoma mRNA encoding the variable domains of the light (VL) and heavy (VH) c... more The cDNA of heterohybridoma mRNA encoding the variable domains of the light (VL) and heavy (VH) chains of an IgG1 bovine monoclonal antibody (MAb) neutralizing bovine herpesvirus 1 was commercially synthesized, cloned and sequenced. The variable (V) light chain sequence had highest identity with members of the V lambda family, 1a subfamily, and the joining (J) gene JL3, both commonly expressed in cattle. The V heavy chain sequence had highest identity with members of the VH1 gene family and JH1, also both commonly expressed in cattle. The VH nucleotide sequence had highest identity with the bovine diversity (D) gene DH3. The derived amino acid sequences were used to examine the complementarity-determining regions (CDRs) according to multiple systems. CDRL1-3 and CDRH1-2 were identified as belonging to or being similar to known canonical classes, and results from “H3 rules” were determined for CDRH3. Models of the Fv structure were derived using three on-line software packages. Overlapping sets of rodent and human MAb were used by the packages as templates for each framework and CDR structure individually. Predictions of the CDRL3 and CDRH3 configurations were more variable than that of other CDRs, and resulted in different paratope models. The results suggest sequences and crystal structures of MAb from a variety of species may be useful in describing additional canonical structures of immunoglobulins.
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Veterinary Immunology and Immunopathology, May 1, 2014
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Journal of Immunology, May 1, 2014
The cDNA of heterohybridoma mRNA encoding the variable domains of the light (VL) and heavy (VH) c... more The cDNA of heterohybridoma mRNA encoding the variable domains of the light (VL) and heavy (VH) chains of an IgG1 bovine monoclonal antibody (MAb) neutralizing bovine herpesvirus 1 was commercially synthesized, cloned and sequenced. The variable (V) light chain sequence had highest identity with members of the V lambda family, 1a subfamily, and the joining (J) gene JL3, both commonly expressed in cattle. The V heavy chain sequence had highest identity with members of the VH1 gene family and JH1, also both commonly expressed in cattle. The VH nucleotide sequence had highest identity with the bovine diversity (D) gene DH3. The derived amino acid sequences were used to examine the complementarity-determining regions (CDRs) according to multiple systems. CDRL1-3 and CDRH1-2 were identified as belonging to or being similar to known canonical classes, and results from “H3 rules” were determined for CDRH3. Models of the Fv structure were derived using three on-line software packages. Overlapping sets of rodent and human MAb were used by the packages as templates for each framework and CDR structure individually. Predictions of the CDRL3 and CDRH3 configurations were more variable than that of other CDRs, and resulted in different paratope models. The results suggest sequences and crystal structures of MAb from a variety of species may be useful in describing additional canonical structures of immunoglobulins.
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Animal health research reviews / Conference of Research Workers in Animal Diseases, 2013
Bovine herpesvirus 1 (BHV-1) infection is widespread and causes a variety of diseases. Although s... more Bovine herpesvirus 1 (BHV-1) infection is widespread and causes a variety of diseases. Although similar in many respects to the human immune response to human herpesvirus 1, the differences in the bovine virus proteins, immune system components and strategies, physiology, and lifestyle mean the bovine immune response to BHV-1 is unique. The innate immune system initially responds to infection, and primes a balanced adaptive immune response. Cell-mediated immunity, including cytotoxic T lymphocyte killing of infected cells, is critical to recovery from infection. Humoral immunity, including neutralizing antibody and antibody-dependent cell-mediated cytotoxicity, is important to prevention or control of (re-)infection. BHV-1 immune evasion strategies include suppression of major histocompatibility complex presentation of viral antigen, helper T-cell killing, and latency. Immune suppression caused by the virus potentiates secondary infections and contributes to the costly bovine respir...
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Animal health research reviews / Conference of Research Workers in Animal Diseases, 2013
Bovine herpesvirus 1 (BHV-1) causes a variety of diseases and is globally distributed. It infects... more Bovine herpesvirus 1 (BHV-1) causes a variety of diseases and is globally distributed. It infects via mucosal epithelium, leading to rapid lytic replication and latent infection, primarily in sensory ganglia. Large amounts of virus can be excreted by the host on primary infection or upon recrudescence of latent infection, resulting in disease spread. The bovine immune response to BHV-1 is rapid, robust, balanced, and long-lasting. The innate immune system is the first to respond to the infection, with type I interferons (IFNs), inflammatory cytokines, killing of infected host cells, and priming of a balanced adaptive immune response. The virus possesses a variety of immune evasion strategies, including inhibition of type I IFN production, chemokine and complement binding, infection of macrophages and neutrophils, and latency. BHV-1 immune suppression contributes to the severity of its disease manifestations and to the bovine respiratory disease complex, the leading cause of cattle d...
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Cytotechnology, 1998
Contamination of animal-derived raw materials with viruses, mycoplasmas, bacteria and fungi is co... more Contamination of animal-derived raw materials with viruses, mycoplasmas, bacteria and fungi is common. These contaminants can interfere with the diagnosis of viral infection, and vaccines produced using infected cell cultures could lead to seroconversion or disease in the vaccinated animal. The purity, safety and efficacy of viral vaccines requires testing of the ingredients, cell substrates and final product. Methods for detection of viruses, especially bovine viral diarrhea virus, in nutrient serum, cell cultures, seed viruses and viral vaccines, and the frequency of their detection at the Center for Veterinary Biologics are discussed.
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Journal of the American Veterinary Medical Association, 1994
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Veterinary Immunology and Immunopathology, 2015
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Papers by Randall L. Levings