Developments in biologicals最新文献

Foot-and-mouth disease virus (FMDV) exists as multiple serotypes and strains that infect a range of cloven-hoofed animals with variable severity. Clinical diagnosis reinforced by diagnostic tests support timely intervention, whilst virus characterisation helps trace routes of spread and select appropriate vaccine strains. To speed up and simplify diagnosis, penside tests have recently been developed. Serology is used to identify undisclosed infection and substantiate freedom from infection and specific tests are needed to detect infected animals in vaccinated populations. Serology is also used to estimate post-vaccinal population immunity. Contingency plans are required to enable countries to scale up diagnosis at short notice. Improvements are needed in preclinical and penside diagnosis and in our ability to model vaccine effectiveness.

African swine fever virus is a large DNA virus which can cause an acute haemorrhagic fever in pigs resulting in high mortality. No vaccine is available, limiting options for control. The virus encodes up to 165 genes and virus particles are multi-layered and contain more than 50 proteins. Pigs immunised with natural low virulence isolates or attenuated viruses produced by passage in tissue culture and by targeted gene deletions can be protected against challenge with virulent viruses. CD8+ cells are required for protection induced by attenuated strain OURT88/3. Passive transfer of antibodies from immune to naïve pigs can also induce protection. Knowledge of the genome sequences of attenuated and virulent strains and targeted gene deletions from virulent strains have identified a number of virus genes involved in virulence and immune evasion. This information can be used to produce rationally attenuated vaccine strains. Virus antigens that are targets for neutralising antibodies have been identified and immunisation with these recombinant proteins has been shown to induce partial protection. However knowledge of antigens which encode the dominant protective epitopes recognised by CD8+ T cells is lacking.

Since 1959, 32 epizootics of high pathogenicity avian influenza (HPAI) have occurred in birds. Rapid detection and accurate identification of HPAI has been critical to controlling such epizootics in poultry. Specific paradigms for the detection and diagnosis of avian influenza virus (AIV) in poultry vary somewhat among different countries and industry compartments depending on specific needs and resources. Importantly, since HPAI and low pathogenicity (LP) AI of the H5 and H7 subtypes are reportable to the World Organization for Animal Health (OIE), diagnostic procedures are implemented for regulatory purposes and are harmonized to some degree. Most current tests are adequate and have been in use for some time, therefore they have been well validated and presently there is no reported new technology that will completely replace the current tests. However, some modifications, updates or additional tests could be beneficial. The element of AIV diagnostics that is most in need of improvement is in determining the hemagglutinin and neuraminidase subtype specificity of antibody to AIV. Most HPAI epizootics have been eradicated using traditional stamping-out programs, but beginning in 1995, five epizootics have added vaccination as an additional, interim control tool. From 2002-2010, >113 billion doses of AI vaccine have been used in poultry; 95.5% as oil-emulsified, inactivated whole AIV vaccines and 4.5% as live vectored vaccines. The majority of vaccine has been used in the four H5N1 HPAI enzootic countries (China [91%], Egypt [4.7%], Indonesia [2.3%], and Vietnam [1.4%]) where vaccination programs are directed to all poultry. The 10 other countries/regions have used less than 1% of the vaccine, administered in a focused, risk- based approach. Some vaccine "failures" have resulted from antigenic drift of field viruses away from the vaccine viruses, but most have resulted from failures in the vaccination process; i.e. failure to adequately administer the vaccine to at risk poultry resulting in lack of population immunity. China, as the major AIV vaccine user, will drive innovation and commercialization of new vaccine technologies, but because of the low-cost to manufacture the current high quality inactivated whole AIV vaccines, such vaccines will continue to dominate the market for the next 10 years.

Disease outbreaks caused by arthropod-borne animal viruses (arboviruses) resulting in significant livestock and economic losses world-wide appear to be increasing. Rift Valley fever (RVF) virus is an important arbovirus that causes lethal disease in cattle, camels, sheep and goats in Sub-Saharan Africa. There is concern that this virus could spread because of global warming, increased animal trade or through bioterrorism. This paper discusses the current and developing approaches to diagnosis of RVF. Diagnostic assays are available for RVF, but availability can be limited and there is a need for global harmonization. Continued improvement of standard serological and viral genome amplification approaches, including new embedded/syndromic testing, biosensor, emerging virus detection and characterization technologies is needed.

African swine fever (ASF) is one of the most complex livestock diseases. The significant losses that it causes, coupled with the lack of a vaccine against ASF virus and the possible resemblance with other swine hemorrhagic diseases, make early detection and laboratory diagnosis essential for controlling and managing the disease. All the techniques currently used to diagnose ASF have been fully validated showing high sensitivity and specificity to detect both antigen and antibodies against all 22 known genotypes; and enable the correct diagnosis of ASF in all possible epidemiological situations. Because no vaccine is available, the presence of antibodies always indicates previous infection, and serological diagnosis must always be performed in parallel with antigen detection to increase the sensitivity and specificity of the analyses. Recent developments in ASF diagnosis, specifically the new field diagnostic tests, have improved and facilitated the likelihood of ASF early detection, essential to fighting the disease.

Ebola viruses (EBOV; genus Ebolavirus, family Filoviridae) cause often fatal, hemorrhagic fever in several species of simian primates including human. While fruit bats are considered a natural reservoir, the involvement of other species in the EBOV transmission cycle is unclear, especially for domesticated animals. Dogs and pigs are so far the only domestic animals identified as species that can be infected with EBOV. In 2009 Reston-EBOV was the first EBOV reported to infect swine with indicated transmission to humans; and a survey in Gabon found over 30% seroprevalence for EBOV in dogs during the Ebola outbreak in 2001-2002. While infections in dogs appear to be asymptomatic, pigs experimentally infected with EBOV can develop clinical disease, depending on the virus species and possibly the age of the infected animals. In the experimental settings, pigs can transmit Zaire-Ebola virus to naive pigs and macaques; however, their role during Ebola outbreaks in Africa needs to be clarified. Attempts at virus and antibody detection require as a prerequisite validation of viral RNA and antibody detection methods especially for pigs, as well as the development of a sampling strategy. Significant issues about disease development remain to be resolved for EBOV. Evaluation of current human vaccine candidates or development of veterinary vaccines de novo for EBOV might need to be considered, especially if pigs or dogs are implicated in the transmission of an African species of EBOV to humans.

The development of countermeasures to support an effective response to Transboundary Animal Diseases (TAD) poses a challenge on a global scale and necessitates the coordinated involvement of scientists from government, industry and academia, as well as regulatory entities. The Agricultural Defense Branch under the Chemical and Biological Defense Division (CBD) of the Department of Homeland Security (DHS), Science and Technology Directorate (S&T) supports this important mission within the United States. This article provides an overview of the Agricultural Defense Branch's vaccine and diagnostic TAD project.

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.

Veterinary diagnostic products generated ~$3 billion US dollars in global sales in 2010. This industry is poised to undergo tremendous changes in the next decade as technological advances move diagnostic products from the traditional laboratory-based and handheld immunologic assays towards highly technical, point of care devices with increased sensitivity, specificity, and complexity. Despite these opportunities for advancing diagnostic products, the industry continues to face numerous challenges in developing diagnostic products for emerging and foreign animal diseases. Because of the need to deliver a return on the investment, research and development dollars continue to be focused on infectious diseases that have a negative impact on current domestic herd health, production systems, or companion animal health. Overcoming the administrative, legal, fiscal, and technological barriers to provide veterinary diagnostic products for the National Veterinary Stockpile will reduce the threat of natural or intentional spread of foreign diseases and increase the security of the food supply in the US.

The need for better foot-and-mouth disease (FMD) vaccines is not new, a report from the Research Commission on FMD, authored by F. Loeffler and P. Frosch in 1897, highlighted the need for developing a vaccine against FMD and qualified this as a devastating disease causing "severe economic damage to the country's agriculture" [1]. Inactivated antigen vaccines have been available since the early 1900s and have been instrumental in eradicating FMD from parts of the world and repressing clinical disease in others. However, these vaccines require using live virulent FMDV for manufacturing, fail to prevent infection resulting in the establishment of carrier animals, require multiple vaccination schedules (every six months) and have limited coverage to the specific serotype and in many cases subtype of FMDV. Therefore, FMD vaccinology continues to be a very active research field. Research-based novel vaccine approaches over the last decade have resulted in at least one novel molecular vaccine being licensed for emergency use in the US and multiple other vaccine approaches being actively pursued as alternatives to current vaccines. Here we will review and update the main research efforts on FMD vaccines, including subunit and peptide vaccines, DNA vaccines, empty capsid vaccines (directly delivered or vector delivered), novel inactivated antigen production platforms and live attenuated vaccines. Each of these approaches will be discussed in terms of their safety and efficacy characteristics, product transition feasibility as well as their applicability to global control and eradication efforts.