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OS18 FOOT-AND-MOUTH DISEASE RESEARCH GAP ANALYSIS WORKSHOP 2018 June 12 th -14 th INTA – Buenos Aires, Argentina Mariano Pérez-Filgueira Institute of Virology, INTA - CONICET

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  • OS18

    FOOT-AND-MOUTH DISEASE RESEARCH

    GAP ANALYSIS WORKSHOP 2018 June 12th-14th INTA – Buenos Aires, Argentina

    Mariano Pérez-FilgueiraInstitute of Virology, INTA - CONICET

  • OS18

    2018

    2010

    2006?

    FOOT-AND-MOUTH DISEASE GAP ANALYSIS WORKSHOPS

  • OS18

    NAME AFFILIATION COUNTRYCharles Nfon CFIA CanadaAlejandra Capozzo INTA-CONICET ArgentinaGuido Konig INTA-CONICET ArgentinaMariano Pérez Filgueira INTA-CONICET ArgentinaMaría Ines Gismondi INTA-CONICET ArgentinaPatricia Zamorano INTA-CONICET ArgentinaSergio Duffy CECSA-UNR ArgentinaSabrina Galdo Novo SENASA ArgentinaIngrid Bergmann CEVAN-CONICET ArgentinaEliana Smitsaart Biogénesis-Bagó ArgentinaAna María Espinoza Biogénesis-Bagó ArgentinaMarianna Ióppolo ZoetisJustin Widener MerialAlasdair King MerckFrançois Maree OVI-ARC S. AfricaFrank Mwiine Makerere Univ. UgandaAbraham Sangula Vet. Serv. Dict. Kenya

    NAME AFFILIATION COUNTRYCyril Gay USDA USAElizabeth Rieder PIADC-ARS USAJonathan Arzt PIADC-ARS USATeresa De Los Santos PIADC-ARS USAConsuelo Carrillo PIADC-APHIS USALuis Rodríguez PIADC-ARS USAManuel Borca PIADC-ARS USAAndrés Perez Univ. of Minnesota USARichard Reeve Univ. of Glasgow UKDonald King Pirbright Inst./WRL UKWilna Vosloo CSIRO AustraliaDah Dung Min. Agri. & Rural Dev. VietnamZhidong Zhang Lanzhou Inst. ChinaStefano Messori OIEM. Sánchez Vázquez PANAFTOSA

    ü Researchers from different areas of knowledge

    ü Government officials

    ü Regulatory officers

    ü Vaccine manufacturers

  • OS18

    TUESDAY 12 JUNE WEDNESDAY 13 JUNE THURSDAY 14 JUNE

    Introduction and presentations Host-Pathogen interactions: FDMV/host interactome. Pathogenesis and persistence: mechanisms related to the carrier state (MAREE/ARZT)

    Epidemiology: global distribution and burden of FMD /changes in the seven pools? (KING/NFON)Virology: viral evolution and discovery of

    determinants of virulence (RIEDER/DE LOS SANTOS) Coffee break Coffee break

    Coffee break Host-Pathogen interactions: protective responses, breadth of protection (heterologous protection) (CAPOZZO/ M.PEREZ)

    Epidemiology: molecular epidemiology and modelling (transmission, outbreaks) (KONIG/A.PEREZ)Virology: host range/adaptation (ARZT/MAREE)

    Wrap-up by thematic unitsLunch Lunch Lunch

    Diagnostics: in vitro assays for assessing vaccine quality (matching and potency) (CARRILLO/CAPOZZO)

    Vaccines: commercial vaccines, new vaccine technologies, and biotherapeutics/antivirals (DE LOS SANTOS/RIEDER)

    Closure

    Coffee break Coffee break

    Diagnostics: for detection, freedom from infection (with or without vaccination), AND herd immunity (NFON/ZHANG)

    Vaccines: protection according to the target species. Challenges in global supplies of FMD vaccines (VOSLOO/SMITSAART)

    FOOT-AND-MOUTH DISEASE RESEARCH GAP ANALYSIS WORKSHOP 2018 June 12th-14th INTA – Buenos Aires, Argentina

  • OS18

    FOOT-AND-MOUTH DISEASE VACCINES: CURRENT OBSTACLES ü Conventional inactivated FMD vaccines cannot be manufactured outside BSL3

    containment facilities

    ü Current monovalent vaccines provide only serotype/strain-specific protection

    ü Antigen drift within serotypes requires ongoing expense to stockpile newly emerging antigens.

    ü Current vaccines allow a window of vulnerability at the beginning of the responses and do not provide long-lasting immunity

    ü No currently available vaccine provides “sterile immunity” (preventing subsequent infections and/or persistently infected animals)

    ü Absence of different vaccine alternatives “fit for purpose” according to regional needs and ecological settings

    ü Presence of residual NSPs in some commercial formulations prevents the implementation of effective DIVA strategies

    ü Absence of standardized vaccine QC tests (potency, purity, strain identity, antigen payload) allow significant variations among commercial FMD vaccines

    ü Harmonized QC methods tailored for antigen banks

  • OS18

    ü New and improved methods to concentrate and purify vaccine whole capsid antigens from NSP allowing conventional formulations to be used as high

    potency DIVA vaccines (in process NSP content control assays also available for

    vaccine manufacturers)

    ü Ad5-vectored vaccines (replication defective)• tested in cattle and swine with good protective results (3ABC companion

    test also developed for DIVA use)

    • vaccines developed for strains from the A, O, Asia 1 and SAT2 serotypes • minimum immunizing dose studies completed and a vaccine release dose

    has been approved

    • Combination with Ad5-vectored IFNs may promote the onset of protective responses from 1 or 2 days post-vaccination

    FOOT-AND-MOUTH DISEASE VACCINES: DEVELOPMENTS SINCE 2010

  • OS18

    ü VLP-based vaccines• Development of reliable platforms (baculovirus, mammalian cell cultures) • New gene constructions to produce VLP-based vaccines for different strains with

    improved production yields• Structural studies on the viral capsid revealed new strategies to improve thermal

    stability for selected strains• Successful efficacy studies in target species

    ü DIVA marker cDNA-derived inactivated FMDV vaccine (FMD-LL3B3D) • Includes negative markers for DIVA use (no need to remove NSP for production)• Leader-less design renders a highly attenuated virus (reduced escape risk)• Designed for easy swapping of capsid protein sequences from different strains• Sequence backbone derived from a strain well-adapted to BHK growth• Platform easily adaptable to current vaccine manufacturing processes

    FOOT-AND-MOUTH DISEASE VACCINES: DEVELOPMENTS SINCE 2010

  • OS18

    ü Testing and development of new adjuvants and formulations: improve interaction between private sectors and researchers (public organizations)

    ü Vaccines promoting sterile immunity

    ü New vaccine delivery methods

    ü Define relevant immunological parameters (besides antibody titers) for:i. indirect assessment of vaccine efficacy (avoiding challenge) in different

    target speciesii. vaccine design “fit for purpose” according to animal species and

    ecological/geographical settings

    FOOT-AND-MOUTH DISEASE VACCINES: CURRENT GAPS

  • OS18FOOT-AND-MOUTH DISEASE IMMUNITY: ADVANCES SINCE 2010

    ü Immune response against FMDV infection in cattle is T-independent and IgM responses drives virus clearance

    ü Aerogenous infection promotes genuine local responses in cattle

    ü Parenteral vaccination in cattle induces mucosal adaptive responses as well as secondary responses upon aerosol infection

    ü CD4+ T-cell responses are required for inducing protection after vaccination

    ü IFN-γ T-cell responses are cross-reactive and depend on the capsid integrity

    ü Maternal immunity may counteract the development of neutralizing antibodies in calves but does not affect virus-specific T-cell responses

    ü Protection can be achieved with low antibody titers (immunological memory); quality of the antibodies induced is related to cross-protection (avidity, IgG subtypes)

    ü Circulating systemic antibodies, in the absence of other immunological processes, can prevent FMD after aerogenous challenge

  • OS18FOOT-AND-MOUTH DISEASE IMMUNITY: CURRENT GAPS

    ü Define immunological mechanisms involved in protection against homologous and heterologous virus infection

    ü Study the mechanisms that lead to the establishment and longevity of memory responses

    ü Define the importance of cell-mediated immune responses and innate immunity in protection

    ü Identify immunological parameters induced by multivalent vaccines, vaccination schedules, and antigen payload in protection against heterologous infections

    ü Big data analysis for identification of genes involved in immune responses: understand protective immunity and help in design of new strategies (vaccines, adjuvants, etc.) targeting innate and adaptive responses (rapid onset and long-lasting protection)

    ü Understanding the structural rules governing Ab-Ag interactions to provide molecular basis for vaccine design

  • OS18

    ACKOWLEDGEMENTS

    Cyril Gay

    Luis Rodríguez

    Guido Konig

    Alejandra Capozzo

    The Participants!Jonathan Arzt, Ingrid Bergmann, Manuel Borca, Consuelo Carrillo,

    Teresa De Los Santos, Sergio Duffy, Dah Dung, Ana María Espinoza,

    Sabrina Galdo Novo, María Ines Gismondi, Marianna Ióppolo,

    Alasdair King, Donald King, François Maree, Stefano Messori, Frank

    Mwiine, Charles Nfon, Andrés Perez, Richard Reeve, Elizabeth Rieder,

    Abraham Sangula, Eliana Smitsaart, Manuel Sánchez Vázquez, Wilna

    Vosloo, Justin Widener, Patricia Zamorano and Zhidong Zhang

    FOOT-AND-MOUTH DISEASE RESEARCH

    GAP ANALYSIS WORKSHOP 2018 June 12th-14th INTA – Buenos Aires, Argentina


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