Slide1: Lecture No. 20 - April 22nd, 2004
International Aspects of
Veterinary Vaccines and Diagnostics
James Roth
International Aspects of Veterinary Vaccines and Diagnostics April 22, 2004 : International Aspects of Veterinary Vaccines and Diagnostics April 22, 2004 James A. Roth, DVM, PhD
Department of Veterinary Microbiology and Preventive Medicine
College of Veterinary Medicine
Iowa State University, Ames, Iowa 50011
Phone 515 294 8459
E-mail jaroth@iastate.edu
Worldwide Importance of Animal Health Professionals: Worldwide Importance of Animal Health Professionals Need for food production
Zoonotic diseases
Food Safety
Foreign animal diseases
Emerging diseases
Bioterrorism/Agroterrorism
World Population Growth (United Nations Projection): World Population Growth (United Nations Projection)
Past and Projected Consumption Trends of Meat, to the Year 2020: Past and Projected Consumption Trends of Meat, to the Year 2020
Use of Vaccines in the US: Use of Vaccines in the US The US is the largest market for manufacturers of veterinary vaccines and accounts for 23% of the $2 billion per year in worldwide sales of veterinary biologics.
North America and the European Union together account for almost 50% of the worldwide sales of veterinary biologics.
Distribution and Use of Vaccines in the US: Distribution and Use of Vaccines in the US There are over 1220 vaccine formulations approved by the USDA for use in domestic animals in the US.
There are approximately 115 licensed manufacturers of veterinary vaccines in the US.
Veterinary Vaccines Licensed for Production and Sale in the US: Veterinary Vaccines Licensed for Production and Sale in the US
Slide9: Office International des Épizooties
World Organisation for Animal Health
created in 1924 in Paris
OIE List A Diseases are:: OIE List A Diseases are: Transmissible diseases which have the potential for very serious and rapid spread, irrespective of national borders, which are of serious socio-economic or public health consequence and which are of major importance in the international trade of animals and animal products.
OIE List B Diseases are:: OIE List B Diseases are: Transmissible diseases which are considered to be of socio-economic and/or public health importance within countries and which are significant in the international trade of animals and animal products.
OIE List A Diseases that are Presently in the United States: OIE List A Diseases that are Presently in the United States Blue tongue
Vesicular stomatitis
OIE List A Diseases that are not Presently in the United States: OIE List A Diseases that are not Presently in the United States Foot and Mouth Disease
Swine Vesicular Disease
Rinderpest
Peste des Petits Ruminants
Contagious Bovine Pleuropneumonia
Lumpy Skin Disease
OIE List A Diseases that are not Presently in the United States: OIE List A Diseases that are not Presently in the United States Rift Valley Fever
Sheep Pox and Goat Pox
African Horse Sickness
African Swine Fever
Hog Cholera
Highly Pathogenic Avian Influenza
Newcastle Disease
Vaccines for OIE List A and Emerging Animal Diseases: Vaccines for OIE List A and Emerging Animal Diseases September 16-18, 2002, Ames, Iowa
The purpose of the meeting was to review the availability, safety and efficacy of veterinary vaccines for OIE List A diseases and for selected emerging animal diseases
Publication:
Vaccines for OIE List A and Emerging Animal Diseases. Developments in Biologicals, F. Brown and J. A. Roth, Eds. Vol 114, 295 pages, 2003
A Survey of Vaccines Produced for OIE List A Diseases in OIE Member Countries James A. Roth, Anna R. Spickler, Developments in Biologicals, F. Brown and J. A. Roth, Eds. Vol 114:5-25, 2003: A Survey of Vaccines Produced for OIE List A Diseases in OIE Member Countries James A. Roth, Anna R. Spickler, Developments in Biologicals, F. Brown and J. A. Roth, Eds. Vol 114:5-25, 2003
A questionnaire was sent by the OIE to the Chief Veterinary Officer of all OIE member nations: A questionnaire was sent by the OIE to the Chief Veterinary Officer of all OIE member nations For each OIE List A disease:
Does your country manufacture a vaccine?
Strain of organism used?
Type of product?
Adjuvant?
Contact information for the manufacturer?
Response: Response Sixty-four countries responded
31 do not manufacture vaccines for list A disease
33 do manufacture vaccines for list A diseases
Number of Vaccines: Number of Vaccines African Horse Sickness
African Swine Fever
Bluetongue
Classical Swine Fever
Contagious Bovine Pleuropneumonia
Foot and Mouth Disease
Avian Influenza
Lumpy Skin Disease
4
0
2
42
2
30
3
2
Number of Vaccines: Number of Vaccines Newcastle Disease
Peste des Petits Ruminants
Rift Valley Fever
Rinderpest
Sheep and Goat Pox
Swine Vesicular Disease
Vesicular Stomatitis Virus >200
2
4
5
5
0
3
Slide21: Office International des Épizooties
World Organisation for Animal Health
created in 1924 in Paris
Slide22: 162 Member Countries (May 2002) Americas: 28 – Africa: 47 – Europe: 49 – Middle East: 12 – Asia: 26
OIE Objectives: OIE Objectives To ensure transparency in the animal health situation throughout the world.
To collect, analyse and disseminate scientific veterinary information.
To contribute expertise and encourage international solidarity in the control of animal diseases.
Within its mandate under SPS and WTO Agreement, to safeguard world trade by publishing health standards for international trade in animals and animal products.
5. To improve the legal framework and resources of Veterinary Services.
Slide24: INTERNATIONAL COMMITTEE
Administrative Commission Specialist Commissions Code, Standards, Fish, Foot and Mouth Disease Regional Commissions
Africa, Americas, Europe, Asia- Far East and Oceania, Middle East Central Bureau Director General Regional Activities
Department Administrative
and Financial
Department Animal Health
Information
Department Publications
Department Scientific and
Technical
Department International Trade
Department
OIE Information System: OIE Information System Promotes transparency and improves knowledge of Global Animal Disease Situation
OIE Early Warning System based on official reports from Member Countries
Active search and verification of non official information
Improve data quality at the field level
OIE Global Information System
Slide26: The OIE
Early
Warning
System
OIE International Standards: OIE International Standards International Animal Health Code - mammals, birds and bees
International Aquatic Animal Health Code – fish, molluscs and crustaceans
Manual of Standards for Diagnostic Tests and Vaccines
Diagnostic Manual for Aquatic Animal Diseases
Guidelines for the Surveillance of Animal Diseases
OIE International Animal Health Code: OIE International Animal Health Code The OIE International Animal Health Code is a reference document for use by authorities of veterinary departments, import/export services, and anyone involved in international trade.
Manual of Standards: Manual of Standards The purpose of the manual is to contribute to the international harmonization of methods for the surveillance and control of the most important animal diseases. Standards are described for laboratory diagnostic tests and the production and control of biological products for veterinary use across the globe.
Aquatic Code: Aquatic Code The Code provides detailed definitions of minimum health guarantees required of trading partners in order to avoid the risk of spreading aquatic animal diseases, and includes sections on import risk analysis and import/export procedures.
The Bulletin: The Bulletin The Bulletin, published in English, French and Spanish, contains data received each month from national Veterinary Services on the occurrence of new outbreaks of animal diseases, giving priority to the 15 diseases of OIE List A.
World Animal Health in 2002: World Animal Health in 2002 Part 1 compiles the most significant epidemiological events which occurred in 2002 including statistical data on new outbreaks of the most contagious and economically important diseases (OIE List A) which occurred during the year.
World Animal Health in 2002: World Animal Health in 2002 Part 2 is composed of tables providing data by country, on the impact of the 15 List A diseases and the 90 diseases of List B. The tables include the number of outbreaks, cases and death.
Information on the Web www.oie.int: Information on the Web www.oie.int Weekly Disease Information
International Standards (Code, Manual, etc.)
Veterinary biotechnology Database
Scientific and Technical Review (contents and abstracts)
General information
Collaborating Centres and Reference Laboratories: Collaborating Centres and Reference Laboratories Collaborating Centres
Reference laboratories for diagnosis, control, research and training
Slide36: Institute for International Cooperation in Animal Biologics OIE Collaborating Centre for Diagnosis of Animal Disease and Vaccine Evaluation in the Americas
USDA ISU
Ames, Iowa USA
Institute for International Cooperation in Animal Biologics: Institute for International Cooperation in Animal Biologics USDA Animal and Plant Health Inspection Service, Veterinary Services
Center for Veterinary Biologics
National Veterinary Services Laboratories
USDA Agriculture Research Service
National Animal Disease Center
Iowa State University
College of Veterinary Medicine
OIE/IICAB Veterinary Biologics Training Program, May 12-28, 2004: OIE/IICAB Veterinary Biologics Training Program, May 12-28, 2004 Block 1: Basic Immunology and Principles of Vaccination (May 12-14)
Block 2: Procedures for Ensuring Vaccine Safety and Efficacy (May 17-21)
Block 3: Potency and Safety Testing and Diagnostic Test Kit Evaluation (May 24-26)
Block 4: Tours of production facilities (for international government regulatory officials only) (May 27-28)
Agroterrorism: Agroterrorism The Soviet Union and Iraq are both known to have developed biological weapons targeting domestic animals and crops.
Bin Ladin called for attacks on the U.S. economy.
Homeland Security Presidential Directive 9: Defense of US Agriculture and Food: Homeland Security Presidential Directive 9: Defense of US Agriculture and Food Published January 30, 2004
Directs the establishment of a “National Veterinary Stockpile containing sufficient amounts of animal vaccine, antiviral, or therapeutic products to appropriately respond to the most damaging animal diseases”
Characteristics of an Effective Agent Against Animals: Characteristics of an Effective Agent Against Animals Highly contagious, infectious, and pathogenic
Survives well in environment
Easy to obtain and grow
Outbreak attributable to natural circumstances
Cause an import ban by other countries
Induce economic hardship
Foreign animal disease (FAD)
U.S. animals highly susceptible
Potential Agroterrorism Pathogens: Potential Agroterrorism Pathogens Foot-and-mouth disease virus
African horse sickness virus
African swine fever virus
Avian influenza virus
Hog cholera virus
Lumpy skin disease virus
Newcastle disease virus
Peste des petits ruminants virus
Rinderpest virus
Vesicular stomatitis virus
Others
Potential Bioterrorism Pathogens: Potential Bioterrorism Pathogens Zoonotic pathogens
Rift Valley fever virus
Eastern, Western, and Venezuelan Equine Encephalitis
Nipah virus
Bacillus anthracis
Brucella spp.
Burkholderia spp.
Francisella tularensis
Yersinia pestis
Others
Emerging Diseases: Emerging Diseases Over the past 20 years an average of one new serious infectious disease threat of military importance has emerged every year somewhere in the world. HIV/AIDS and Ebola are examples.
Causes of Infectious Disease Emergence: Causes of Infectious Disease Emergence Deforestation
Intensive animal housing
Mixing of species
Increased trade travel and migration
Poor sanitation and hygiene
War and civil disorder
Climate change
Over use of antibiotics
Nipah Virus: Nipah Virus Paramyxovirus first isolated in March 1999 in Malaysia
Respiratory and neurologic syndrome in swine
Encephalitis in humans (more than 200 cases, with more than 100 deaths)
Initially mistaken for Japanese encephalitis virus
Slaughter eradication program (more than a million pigs slaughtered)
Agent: Agent Paramyxovirus
Related to Hendra virus
New genus: Henipavirus
Unusual among Paramyxoviruses
Infection and fatal disease in several species
Human, porcine, equine, canine, feline Photo from CDC
Reservoir: Reservoir Flying foxes (fruit bats)
Carry the virus
Are not affected
Virus found in
Urine
Partially eaten fruit
Migratory in most of SE Asia
Slide51: Nipah Field Investigations - Malaysia
Major Challenges for Vaccine Development: Major Challenges for Vaccine Development Biosafety level 4 pathogen
Access to viral genetic material
Foreign animal disease
Recombinant vaccine work in BL2+ lab and BL3 Ag animal facility
USDA Import permits
Proprietary rights to vaccine vectors
USDA APHIS Center for Veterinary Biologics approval for vaccine transport, use, and export
Funding
Nipah Virus Vaccine and Companion Diagnostic Test Development: Nipah Virus Vaccine and Companion Diagnostic Test Development Collaborative project between
Veterinary Research Institute of Malaysia
ISU College of Veterinary Medicine
US Centers for Disease Control and Prevention
USDA Plum Island Animal Disease Center
USDA APHIS National Veterinary Services Laboratories
Canadian Food Inspection Agency
Merial Animal Health
Collaborators: Collaborators Veterinary Research Institute, Ipoh, Malaysia
Aziz Jamaludin, DVM, PhD; Jasbir Singh, DVM, MS
Experience with Nipah virus diagnostics
Supply known positive swine sera
Design and conduct studies to evaluate vaccine and diagnostic test if there is another outbreak of Nipah
Collaborators: Collaborators Iowa State University, College of Veterinary Medicine
James A, Roth, DVM, PhD; Ratree Platt, DVM, PhD
Coordinate project
Seek funding
USDA ARS
NIH
Evaluate antibody and T cell responses to vaccine
Evaluation of Antibody and T Cell Responses: Evaluation of Antibody and T Cell Responses Biosafety Level 4 Agent
Use 2 different recombinant vectors expressing F and G Proteins (eg. Canarypox virus and Human Adenovirus 5)
Immunize pigs with one live virus vector, and use the other vector for in vitro antibody and CMI assays
Assays for T Cell Mediated Immunity: Assays for T Cell Mediated Immunity Monitor activation marker (CD25) expression on T cell subsets using flow cytometry following in vitro incubation with antigen
Assay gamma interferon and IL10 production in vitro by lymphocytes after incubation with antigen
Collaborators: Collaborators Centers for Disease Control and Prevention, Atlanta, Georgia
Paul Rota, PhD
Provide plasmids with Nipah F and G genes
Clone Nipah N gene into Bacculovirus expression vector
Develop and validate ELISA to detect antibody vs Nipah N protein
Conduct serum neutralization assays
Collaborators: Collaborators USDA ARS Plum Island Animal Disease Center
Dan Rock, PhD; Greg Mayr, PhD
Clone F and G genes into Pseudorabies virus and Human Adenovirus 5 vectors
Confirm expression in vitro
Immunize pigs to confirm expression in vivo and freedom from FMD
Collaborators: Collaborators USDA APHIS National Veterinary Services Laboratories
Sabrina Swenson, DVM, PhD
Monitor Project for APHIS
Consult on serologic assays for antibodies to Nipah F, G, and N
House pigs in BL3 Ag facilities for vaccine response studies
Collaborators: Collaborators Merial Limited, Duluth, Georgia; Lyon, France; Toronto, Canada
Robert Nordgren, PhD, Jean-Christophe Audonnet, DVM, PhD
Construct Canarypox vector expressing Nipah F and G proteins
Manufacture bulk quantities of vaccine in USDA licensed facility
Collaborators: Collaborators Canadian Food Inspection Agency, Winnipeg, Canada
Hana Weingartl, PhD
Conduct vaccination challenge studies in BL4 animal facility
Titrate Nipah virus in vaccinated challenged pigs
Serum neutralization assays
What to Remember: What to Remember Role of the OIE
List A diseases
Disease reporting
International Animal Health Code
Manual of Standards
Characteristics of effective agroterrorism agents
Potential agroterrorism and zoonotic agents
Causes of infectious disease emergence
Importance of Agriculture in the U.S., 1997: Importance of Agriculture in the U.S., 1997 Agricultural industry valued at $224 billion
generated $1 trillion in agricultural activities in 1997
Exports account for $140 billion
860,000 jobs
Heavily tied to other industries and sectors
U.S. Animal Data, 2001: U.S. Animal Data, 2001
Livestock Industry: Livestock Industry Vulnerability
Concentrated and intensive nature of US farming
Livestock auctions
Extensive inter/intrastate transport of animals
Centralized feed supply and distribution
Lack of on farm biosecurity and surveillance
Limited, if any, immunity to FADs
Expanded international trade and travel
Infectious agents are widespread in other countries
Slide72: The OIE Global Information System
OIE International Animal Health Code: OIE International Animal Health Code The appendices of the Code provide a series of recommendations devoted to the hygienic collection and handling of semen and embryos, sanitation of hatcheries and incubators, and transport of animals. In addition, a series of model international health certificates is presented.