REVERSE IMMUNOGENOMICS FOR DEVELOPMENT OF AN ANTITICK VACCINE FOR CATTLE

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REVERSE IMMUNOGENOMICS FOR DEVELOPMENT OF AN
ANTI-TICK VACCINE FOR CATTLE

• A combination of in silico and in vivo screening
  for antigen discovery

Isabel de Miranda Santos Department of
Biochemistry and Immunology Ribeirão Preto
Medical School University of São Paulo
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Ticks - Control and Problems

• Current Control Methods
• ACARICIDES
• Cattle and dog ticks are becoming resistant to
  all acaricides
• Residues of acaricides contaminate beef, milk and
  environment
• Sanitary barriers for exports No certification
  for organic products Acaricides affect
  enthomofauna
• Costs for Livestock
• Global US 17 BILLION (FAO)
• Brazil (largest commercial herd gt200 million
  cattle)
• Losses US 2 BILLION/year (Exports beef US 2,
  419 billion)
• Problems for Public Health
• Tick Borne Diseases (TBDs) Spotted/hemorrhagic
  fevers, encephalitis, tick paralysis, Lyme
  Disease
• Problems for Pets (expanding market)
• TBDs e.g., erlichiosis
• Problems for Ecotourism
• Infestations of properties TBDs
• Global Warming
• Geographic distribution, number of peaks and of
  intensities of infestations are increasing

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Ticks - Causes of Losses for Livestock

• Ticks are hematophagous ectoparasites
• Bites cause stress and blood loss
• Tick saliva is toxic and transmits pathogens
  (TBDs)
• Expense of acaricide poor quality of leather
  
• One tick spits 0,5 ml of saliva into its host
  and ingests 3 ml of blood
• A susceptible bovine can harbor 1000 females
  each lays 4000 eggs

tick
cement
skin
Cortesia de Matias Szabó UFU
CBIOT-UFRGS
Cortesia Ligia Miranda UFGo

• 2005 R 577 million SINDAN

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Alternatives for Acaricides- Vaccines -

• Premises for an anti-ECTOparasite vaccine
• Ticks induce immune responses in their hosts
• Host immunity hampers the blood meal and
  reproductive efficiency of the parasite

Gut of Rhipicephalus sanguineus fed on 3 x
infested resistant host (guinea pig) No iron and
vacuolized gut cells
Gut of Rhipicephalus sanguineus fed on 3 x
infested susceptible host (dog) Presence of iron
in gut intact gut cells
Micrografias são cortesia de Matias Szabó UFU
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Alternatives for Acaricides- Vaccines -

• Current Vaccines on the Market
• 2 vaccines for cattle
• TickGard and TickGard Plus Australia (Willadsen
  et al.)
• Gavac Cuba (de la Fuente et al.)
• Bm86 gut protein from Rhipicepahlus (Boophilus)
  microplus
• TickGard Plus Bm86 Bm95 (also from gut)
• Development used concept of concealed antigen

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Concealed Antigens

• Antigens to which the host is not exposed during
  infestations
• Advantage of concealed antigens
• No evolutionary pressure on tick to
• develop escape mechanisms

Non-immune sera
Immune sera
Endocytosis of fluorescein-labeled BSA by tick
gut cells treated with bovine serum. A and C
normal bovine serum B and D immune serum from
bovines immunized with Bm86 Willadsen et al., J.
Immunol., 1989
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Alternatives for Acaricides- Vaccines -

• Current Vaccines on the Market
• 19 years later efficacy is below needs of
  producers
• Less than 20 efficacy - e.g., 400 down to 300
  ticks/host still intolerable
• Difficult to manage
• requires concomitant use of acaricides (albeit
  lesser amounts)
• weak memory requires revaccinations every THREE
  MONTHS!
• Other vaccines under development
• Peptides derived from Bm86 (Patarroyo et al.)
• Cement protein p64 (Nuttal et al., with Merial)

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Alternatives for Acaricides- Vaccines -

• Why are current commercial anti-tick vaccines
  ineffcient?
• Wrong paradigm for chosing antigens
• Only 1- 2 candidate antigens out of a universe of
  
• several hundred possibilities
• Lack of knowledge about immune correlates of
  protection
• One consequence is lack of good readouts
  /surrogates of protection for screening large
  repertoire of antigens