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Necrotic enteritis (NE) is a widespread infectious disease caused by Clostridium perfringens that inflicts major economic losses on the global poultry industry. Due to regulations on antibiotic use in poultry production, there is an urgent need for alternative strategies to mitigate the negative effects of NE. This paper presents a passive immunization technology that utilizes hyperimmune egg yolk immunoglobulin Y (IgY) specific to the major immunodominant antigens of C. perfringens. Egg yolk IgYs were generated by immunizing hens with 4 different recombinant C. perfringens antigens, and their protective effects against NE were evaluated in commercial broilers. Six different spray-dried egg powders were produced using recombinant C. perfringens antigens: α-toxin, NE B-like toxin (NetB; EB), elongation factor-Tu (ET), pyruvate:ferredoxin oxidoreductase, a mixture of 4 antigens (EM-1), and a nonimmunized control (EC). The challenged groups were either provided with different egg powders at a 1% level or no egg powders (EN). The NE challenge model based on Eimeria maxima and C. perfringens dual infection was used. In Experiments 1 and 2, the EB and ET groups exhibited increased body weight gain (BWG; P < 0.01), decreased NE lesion scores (P < 0.001), and reduced serum NetB levels (P < 0.01) compared to the EN and EC groups. IgY against NetB significantly reduced Leghorn male hepatocellular cytotoxicity in an in vitro test (P < 0.01). In Experiment 3, the protective effect of the IgYs mixture (EM-2) against C. perfringens antigens (NetB and EFTu) and Eimeria antigens (elongation factor-1-alpha: EF1α and Eimeria profilin: 3-1E) was tested. The EM-2 group showed similar body weight, BWG, and feed intake from d 7 to 22 compared to the NC group (P < 0.05). On d 20, the EM-2 group showed comparable intestinal permeability, NE lesion scores, and jejunal NetB and collagen adhesion protein levels to the NC group (P < 0.05). In conclusion, dietary mixture containing antibodies to NetB and EFTu provides protection against experimental NE in chickens through passive immunization., (Published by Elsevier Inc.)

There is a critical need in animal agriculture to develop novel antimicrobials and alternative strategies that will help to reduce the use of antibiotics and address the challenges of antimicrobial resistance. High-throughput gene expression analysis is providing new tools that are enabling the discovery of host-derived antimicrobial peptides. Examples of gene-encoded natural antibiotics that have gained attention include antimicrobial peptides such as human granulysin and its multi-species homolog, namely NK-lysin, which provide a protective response against a broad range of microbes and are a principal component of innate immunity in vertebrates. Both granulysin and NK-lysin are localised in cytolytic granules in natural killer and cytotoxic T lymphocytes. Host-derived NK-lysins that were first described in mammals are also found in avian species, and they have been shown to have antimicrobial activities that could potentially be used to control important poultry pathogens. Morphological alterations observed following chicken NK-lysin binding to Eimeria sporozoites and Escherichia coli membranes indicate damage and disruption of cell membranes, suggesting that NK-lysin kills pathogenic protozoans and bacteria by direct interaction. Genotype analysis revealed that chicken NK-lysin peptides derived from certain alleles were more effective at killing pathogens than those derived from others, which could potentially affect susceptibility to diseases. Although the host-derived antimicrobial peptides described in this paper may not, by themselves, be able to replace the antibiotics currently used in animal production, their use as specific treatments based on their known mechanisms of action is showing promising results.

This review covers the basic biology of the West Nile virus and the host-vector-pathogen interactions that result in significant disease in wild birds, horses and humans. The review describes the basic properties of the virus, cellular infection and the pathogenesis of the disease, and the ecology of virus maintenance, amplification and transmission. Disease epidemiology and risk estimation strategies that are currently in use are also examined, and host immune responses and vaccination practices described. The principles of vector control, exposure control and long-term risks caused by climatic and habitat factors are also included.

The National Animal Health Program at the Agricultural Research Service (ARS), United States Department of Agriculture (USDA), includes research programs dedicated to the defense of animal agriculture against the treat of biological agents with the potential of significant economic harm and/or public health consequences. This article provides a summary of the program and identifies its relevance to national initiatives to protect livestock and poultry as well as global food security. An introduction to setting research priorities and a selection of research accomplishments that define the scope of the biodefense research program is provided.

The first International Symposium on Animal Genomics for Animal Health (AGAH) provided an excellent venue for scientists working in the field of genomics to interact with animal health experts. This paper provides an introduction to genome-enabled tools and highlights some of the research projects in the AGAH proceedings. A brief review of animal genomes, the next generation of genetic markers, and the versatility of genome-enabled technologies and their many applications are discussed.

The current explosion in new high-throughput technologies arising from microbial and animal genomics studies is enabling the analysis of the genome, transcriptome, and proteome and offers the opportunity to gain a better understanding of the molecular pathways underlying pathogen biology, the host immune system, and host-pathogen interactions. These new tools can be applied to veterinary pathogens to overcome some of the current hurdles in the discovery of highly effective vaccines for farmed livestock and poultry.

Veterinary pharmaceutical products generated 14.5 billion U.S. Dollars (USD) in worldwide sales in 2000, with biological products contributing 16.2 percent or 2.3 billion USD. The leading biological products were foot-and-mouth disease (FMD) vaccines, with 284 million USD in sales, representing 26.4 percent of the entire livestock biological business. Despite the potential opportunities for the biologicals industry, non-vaccination policies and undefined control and eradication strategies have deterred the private sector from significant investments in the research and development of vaccines against List A diseases. The primary research focus remains vaccines for infectious diseases that have an impact on current domestic herd health management systems. Changing the vaccine paradigm, investing in new technologies, and creating the future by integrating into key alliances with producers and regulatory authorities will be paramount in protecting our poultry and livestock industries against highly infectious diseases and potential acts of bioterrorism.

International trade in veterinary biological products has been restricted by the following factors: a) concerns that contaminated products could result in the introduction of foreign animal disease agents into the importing country b) differences between countries in the technical requirements for product registration. The provisions of the North American Free Trade Agreement (NAFTA) and the General Agreement on Tariffs and Trade (GATT: now the World Trade Organisation [WTO]) require importation decisions to be science-based and transparent. This requires regulatory agencies to implement valid, credible, and science-based risk analysis models for decision-making. The Veterinary Biologics section of the United States Department of Agriculture, Animal and Plant Health Inspection Service, currently uses a formalized risk analysis model to evaluate the safety risks associated with proposals to field test and license new and biotechnology-derived veterinary biological products. This model for evaluating field tests has been modified to evaluate proposals to import veterinary biological products into the United States of America. The authors describe this risk analysis model, which was specifically designed to evaluate the risks of importing veterinary biological products potentially contaminated with foreign animal disease agents.

Regulatory guidelines for experimental vaccines should encourage scientists in the biological industry to consider safety at the onset of product development. They should aid scientists to develop the necessary information to confirm conclusively the safety characteristics of the vaccine micro-organism. Moreover, these guidelines should be incorporated into a standardized regulatory process. Veterinary Biologics (VB) provides these guidelines in Summary Information Formats. These Summary Information Formats specify the relevant information to submit with a product licence application for conventional and recombinant vector vaccines. This paper compares two Summary Information Formats to demonstrate that, apart from the construction process, the information required to confirm the safety characteristics of conventional and recombinant vaccines is equivalent. A short discussion on the availability of established safety studies for experimental veterinary vaccines is included.

The establishment of appropriate procedures for regulating the commercialization of biotechnology products is an international issue which has been debated extensively in many countries. This paper will discuss the current procedures that have been established for the regulation of biotechnology-derived veterinary biologicals within the United States Department of Agriculture (USDA) and more specifically within Biotechnology, Biologics, and Environmental Protection (BBEP) of the Animal and Plant Health Inspection Service (APHIS). These procedures implement recent BBEP regulatory policy that has been developed to ensure risk-based regulation and avoid excessive restrictions that might curtail the development of biotechnology products.

Vascular smooth muscle cell proliferation is regarded as a key early event in the pathogenesis of atherosclerosis. Heparin-binding growth factor (HBGF)-1 and HBGF-2, also referred to as acidic and basic fibroblast growth factor, are potent mitogens for human vascular smooth muscle cells. These cells coexpress HBGF-1 and HBGF-2 and thus represent a vessel wall source for both polypeptides. In this report, we demonstrate that HBGF-1 and HBGF-2 expression is increased when quiescent human smooth muscle cells are treated with fetal bovine serum. The kinetics of HBGF-1 and HBGF-2 mRNA accumulation following serum treatment are distinct. In addition, HBGF-1 transcripts remain elevated for a longer time period; this may reflect the different decay rates of the HBGF-1 and HBGF-2 mRNAs. Serum-inducible HBGF-1 and HBGF-2 mRNA expression does not occur when RNA synthesis is repressed by actinomycin D but can occur in the presence of cycloheximide, an inhibitor of protein synthesis. Immunoprecipitation experiments indicate that serum treatment also increases HBGF-1 and HBGF-2 production. Smooth muscle cells treated with phorbol 12-myristate 13-acetate or certain combinations of polypeptide growth factors also express increased levels of HBGF-1 and HBGF-2 transcripts. Potential sources for these growth factors in vivo include platelets, macrophages, and T lymphocytes; thus, smooth muscle cells located at sites of vascular injury or inflammation may express elevated levels of HBGF-1 and HBGF-2.

Platelet-derived growth factor (PDGF) may be an important regulator of vascular smooth muscle cell (SMC) replication and migration in vivo. Platelets, macrophages, endothelial cells, and SMC are all potential sources of PDGF in the vessel wall. In this study, we have examined the regulation of PDGF gene expression using human SMC cultured in vitro. These cells express transcripts encoding the PDGF A-chain, but not the B-chain. The addition of serum, phorbol ester, acidic fibroblast growth factor, transforming growth factor-beta, or tumor necrosis factor-alpha to serum-starved SMC increased PDGF A-chain mRNA levels. The cytokines interleukin-1 and -6 had no detectable effect. These results indicate that SMC present at sites of injury or inflammation may express elevated levels of PDGF-AA, which could act locally in an autocrine or paracrine manner.

Platelet-derived growth factor (PDGF) is mitogenic and chemotactic for vascular smooth muscle cells cultured in vitro, and, thus, may play a role in the smooth muscle cell proliferation and migration that occurs during atherosclerotic lesion development. Two related PDGF polypeptides, designated as the A and B chains, form functionally active PDGF-AA, AB, or BB dimers. The PDGF A- and B-chain genes are both transcribed in human umbilical vein endothelial (HUVE) cells and their expression is regulated by cytokines, growth factors, endotoxin, and phorbol ester. We reported previously that the angiogenic polypeptide heparin-binding growth factor (HBGF)-1 induces PDGF A-chain gene expression, but does not affect PDGF B-chain gene expression. In this study, we determined whether mRNA stabilization contributed to this induction by measuring the half-life of PDGF A-chain mRNA in quiescent, HBGF-1-stimulated, and proliferating HUVE cells. PDGF A-chain mRNA levels increase when quiescent HUVE cells are treated with the protein synthesis inhibitor cycloheximide; therefore, the effect of cycloheximide on PDGF A-chain mRNA decay was also investigated. The half-life of PDGF A-chain transcripts in quiescent cells was approximately 2.4 h and neither HBGF-1 nor cycloheximide significantly altered this decay rate. We also estimated the half-life of PDGF B-chain mRNA under the three different growth conditions and in the absence or presence of cycloheximide. The half-life in quiescent cells was approximately 1.8 h and was unaffected by HBGF-1 or protein synthesis inhibition. Therefore, the PDGF mRNAs have similar decay rates in HUVE cells, even though the 3' untranslated region of B-chain transcripts, but not A-chain transcripts, contains AU-rich sequence motifs postulated to confer rapid turnover in vivo.