WHAT CAN BE LEARNED FROM VETERINARY VACCINES; THE DIVA CONCEPT Professor Paul-Pierre PASTORET WORLD ORGANISATION FOR ANIMAL HEALTH (OIE)
RINDERPEST A DREADFUL DISEASE HIGH MORTALITY ECONOMIC AND SOCIAL DISASTER ORIGINATING FROM ASIA AND SPREADING TO EUROPE EXTENDED TO AFRICA LOCAL INCURSIONS IN BRAZIL AND AUSTRALIA
RINDERPEST READY TO BE ERADICATED
DEFINITIONS CONTROL ELIMINATION ERADICATION
RINDERPEST A BIG SCIENTIFIC CHALLENGE: Geert REINDERS Henri BOULEY Robert KOCH Jules BORDET Arnold THEILER Maurice NICOLLE Alexandre YERSIN
THE WAY TO CONTROL RINDERPEST INOCULATION AND THE DISCOVERY OF MATERNAL TRANSMISSION OF IMMUNITY PROPHYLACTIC HYGIENIC MEASURES HETEROLOGOUS VACCINES SERUMINIZATION HOMOLOGOUS VACCINES PLOWRIGHT S ATTENUATED VACCINE
A PLEA FOR VACCINES WHY SHOULD WE DEVELOP VETERINARY VACCINES?: To protect animal health To improve animal welfare To protect public health To protect consumers To protect environment and biodiversity To avoid resistance of pathogens To promote sustainable agriculture and animal production
MASS SLAUGHTERING OF ANIMALS FOR DISEASE CONTROL Ethical and public concerns in developed countries Unacceptable in developing countries
HOWEVER MASS SLAUGHTERING MAY BE NECESSARY
COMING BACK TO RINDERPEST ACCORDING TO FRANK FENNER, TO BE ERADICATED A DISEASE MUST: Be important and serious Absence of sub-clinical infection or silent excretion Absence of contagion during the incubation or prodromic periods Absence of asymptomatic carriers or recurrent access of excretion or disease One virus serotype Seasonal incidence No alternative reservoir THE AVAILABILITY OF AN EFFICACIOUS AND STABLE VACCINE
MARKER VACCINES AND COMPANION DIAGNOSTIC TESTS To cope with asymptomatic carriers of wild virus or recurrent infections Marker (DIVA) vaccines have been developed together with companion diagnostic tests
MARKER VACCINES TWO SYSTEMS PRESENTLY USED: Detection of a serological response against a deleted protein in the vaccine strain Detection of a serological response against a non-structural protein (purified vaccines)
EXAMPLES OF MARKER VACCINES Pseudorabies Infectious bovine rhinotracheitis Classical swine fever Foot-and-mouth disease Equine influenza Several vectored vaccines
Classical swine fever
THE EXAMPLE OF INFECTIOUS BOVINE RHINOTRACHEITIS Previously Vaccines against infectious bovine rhinotracheitis were mainly designed to protect the animal against the clinical signs of the disease following infection; nowadays it is designed for the elimination of the infection in the European Union
BOVINE HERPESVIRUS 1 LATENCY All the naïve animals infected with a wild virus strains become latent carriers All the animals previously vaccinated with an inactivated vaccine become latent carriers after infection with a wild virus strain All the animals vaccinated with an attenuated vaccine become latent carriers after infection with a wild virus strain All the latent wild virus carriers remain so following vaccination with either an inactivated or an attenuated vaccine All the attenuated vaccine strains remain latent in the animal after vaccination
IN AN AREA WHERE THE ANIMALS ARE NOT VACCINATED All the seropositive animals must be considered as latent carriers of a wild virus strain
IN AN AREA WHERE THE ANIMALS ARE VACCINATED WITH A CONVENTIONAL, UNDELETED VACCINE A SEROPOSITIVE ANIMAL MAY BE: Latent carrier of a wild virus strain Latent carrier of an attenuated vaccine strain Latent carrier of a wild virus strain after vaccination with an inactivated vaccine Latent carrier of a wild virus strain after vaccination with an attenuated vaccine
THE SOLUTION: A DELETED VACCINE STRAIN CHARACTERISTICS OF THE PROTEIN CODED BY THE DELETED GENE IN THE VACCINE STRAIN: Be a structural protein (inactivated vaccines) Not be essential in order to produce the vaccine Not be an essential protective immunogen to still have an effective vaccine Induce a significant and long-lasting humoral immune response when present Be present in all wild virus strains Induce an humoral immune response in vaccinated animals when infected by a wild virus strain
MARKER (DIVA) IBR VACCINES WHEN AN ANIMAL IS SEROPOSITIVE AGAINST THE DELETED PROTEIN, IT MUST BE CONSIDERED AS INFECTED BY A WILD VIRUS STRAIN
FOOT AND MOUTH DISEASE THANKS TO VACCINATION FOOT-AND- MOUTH DISEASE WAS ELIMINATED FROM WESTERN EUROPE MASS VACCINATION WAS INTERRUPTED IN 1991 LEADING TO A COMPLETELY NAÏVE POPULATION
THE SOLUTION: A MARKER VACCINE A MARKER VACCINE AGAINST FOOT- AND-MOUTH DISEASE IS BASED ON PURIFICATION OF THE ANTIGEN AND DETECTION OF ANTIBODIES AGAINST NON-STRUCTURAL PROTEINS
Distribution of bluetongue outbreaks PAYS-BAS BELGIQUE ALLEMAGNE FRANCE LUXEMBOURG 0 50 Kilomètres 100 Foyers de FCO (BT8) par date de confirmation Source ADNS 15/09/2006 02/09/2006-15/09/2006 28/08/2006-02/09/2006 27/08/2006-28/08/2006 24/08/2006-27/08/2006 17/08/2006-24/08/2006
Clinical bluetongue in cattle: face Muzzle: ulcerous and necrotic lesions, scabs Nose: ulcers in the nostrils, mucous to mucopurulent nasal discharge Oral cavity: ulcers in the gengiva and the tongue, with hypersalivation Peri-ocular oedema and erythema, lacrymation Submandibular swelling
Clinical bluetongue in cattle: limbs and udder Limbs Œdema Muscular rigidity Interdigital lesions Lameness Udder Œdema and erythema of udder Ulcers on the teats
ELIMINATION OF TERRESTRIAL RABIES IN EUROPE THE LIFE OF A RECOMBINANT VACCINE