Foot and mouth Disease Vaccines Current Status

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Foot and mouth Disease Vaccines - Current Status

• R.Venkataramanan, M.Hosamani, B.P.Sreenivasa
• Indian Veterinary Research Institute
• Hebbal, Bangalore 560 024

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Foot and Mouth Disease in IndiaPresent Status

• Susceptible population
• Cattle 185 millions
• Buffaloes 98 millions
• Sheep 62 millions
• Goats 125 millions
• Pigs 14 millions
• Total Domestic animals 484 millions
• Plus all wild ungulates

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Foot and Mouth Disease in IndiaPresent Status

• Endemic -Serotypes O,A and Asia1 are prevalent
• Serotype C not recorded since 1995
• Direct annual losses gt Rs.20,000 Crores
• Indirect losses (work capacity, growth etc.) much
  more
• Embargo on trade in animals and animal products
• Economically most important disease
• Globally No.1 priority for Control

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Foot and Mouth Disease Control

• Large scale repeated vaccination of animals in
  the identified areas to build up the herd
  immunity
• As the vaccination coverage increases the disease
  incidence comes down and finally gets eliminated
• Europe, South American countries followed this
  strategy to eradicate FMD

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Foot and Mouth Disease Control in IndiaPresent
Status

• FMD CP 100 Govt of India funded
• Started in 10th Plan -Implemented in 54 Districts
  in 8 states
• Full vaccination of all Cattle Buffaloes in the
  target districts
• About 30 Million animals covered
• Vaccination schedule followed twice in a year
• Visible reduction in disease incidence
• Already 8 rounds of vaccination completed
• ASCAD Programme of GOI State Govts
• Implemented in all states
• About 70-85 million animals covered under this
  programme

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FMD Vaccines- History

• 1925 (Vallee Carr) Infected tissue from calves
  inactivated by formaldehyde and used as vaccine
• Waldmann et al (late 1920s) used aluminium
  hydroxide gel as adjuvant with above approach and
  found it useful to improve the immunity
• This vaccine was used in Argentina to immunise
  200,000 cattle and 100,000 sheep and found
  effective but not in pigs

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FMD Vaccines- History

• 1947, Frankel demonstrated that the FMD virus can
  be grown in bovine tongue epithelial cells in
  vitro. This led to increased production of
  vaccine in Holland, Germany France
• 1962, Mowat Chapman - BHK 21 pig kidney cell
  lines for growing FMD virus
• 1962, Capstick et al BHK21 suspension cells for
  growing FMD virus in large scale. This is the
  most important milestone in FMD vaccine
  production

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FMD Vaccines- History

• 1979 Bahnemann - BEI Inactivation of FMD virus in
  large scale. Safe and complete, no tailing effect
• 1980s Work on adjuvants, concentration of
  antigens, dose reduction
• 1990s till date Oil Adjuvanted vaccines
  widely used for all species of animals
• More than 1 Billion doses produced and used
  annually

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Poly A

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Structural proteins
Non-structural proteins (NSPs)
Figure 1. Diagram showing the genomic regions of
the FMDV coding for the structural proteins and
non-structural proteins (NSPs). Polyprotein
undergoes specific cleavage mediated by virus
coded proteases viz. Lpro, 2A and 3C at sites
marked , ?, ? respectively. Structural proteins
self assemble to form capsids following post
translational processing of the polyprotein by
these proteases.
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New generation FMD Vaccines

• 1963, Brown Cartwright - Purification of the
  FMD Virus particle
• 1977, Sanger et al. - Biochemical mapping of the
  virus genome
• 1981, Kleid et al. Expression of the VP1
  protein in E. coli and the fusion protein
  elicited neutralising antibodies in experiment
  animals
• 1989, Acharya et al. - Structure of the virus
  revealed by X ray crystallography
• 1990, Zibert et al. Infectious cDNA

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New generation FMD Vaccines

• Subunit vaccines
• Expression of VP1 in different host systems and
  studying their immunogenicity including plants
  (Wang et al., 2008)
• Expression of P1-2A3C to generate empty virus
  particles in bacteria/yeast/baculovirus systems
  by several workers and testing in animals showing
  limited neutralising antibodies during the last
  8-10 years

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New generation FMD Vaccines

• DNA Vaccines
• Two approaches of using DNA vaccine have been
  used
• P1-2A only or P1-2A 3C DNA constructs tried as
  vaccine. The constructs with 3C works better
• Synthetic Peptide Vaccines
• Bittle et al., 1982 140-160 aa region of VP1
  protein
• Geysen et al., 1984 - Pepscan method-overlapping
  peptides of VP1

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New generation FMD Vaccines

• Hybrid viruses
• Availability of the infectious cDNA against all
  serotypes by now
• Construction of hybrids P1 region from one
  serotype into another by appropriate manipulation
  to produce infectious hybrid viruses
• Presently being attempted by different groups

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New generation FMD Vaccines

• Vectored vaccines
• Saiz et al., 1994 VP1/P1 constructs in vaccinia
  virus used in g pigs showed poor response
• Berinstein et al., 2000 -Recombinant vaccinia
  virus expressing FMDV-P1 has been shown to be
  highly immunogenic in mice inducing antibody
  response lasting for 2 months
• Fowl pox virus also tried using FMDV-P1 region
• In animal experiments, these vaccines did not
  show response equal to conventional vaccines

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New generation FMD Vaccines

• Adenovirus vector vaccine
• Grubman et al., 2003 - Replication defective
  human adenovirus vectors, which lack ability to
  replicate on their own, have been produced. These
  vectors can only grow productively in specific
  cell cultures that provide the missing functions,
  i.e. 293 cells. However, they can infect cells of
  several animal species, including cattle and
  swine.
• Used P1-2A3CD region of FMD virus in these adeno
  virus (HAd5) have been tested successfully in
  cattle
• Holds immense potential

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Ideal Vaccine
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Ideal Vaccine
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Ideal Vaccine
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Conclusion

• FMD Vaccine is one single vaccine produced in the
  largest quantity and used for control
• The present vaccines are effective
• Several newer approaches have been tried with no
  success
• The HAd5 Vector vaccine is the most promising new
  generation vaccine developed and is awaiting
  licence in US
• Good quality vaccines is the need of the day to
  effectively control and eradicate FMD

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Thank you