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Blocking naturally acquired infection

Blocking naturally acquired infection. Glyn Hewinson. Experimental Challenge vs ‘Natural’ (transmission blocking) models of infection. Experimental Challenge Un-natural challenge High dose to ensure all controls are infected. One dose at one time point Challenge organism grown in culture

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Blocking naturally acquired infection

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  1. Blocking naturally acquired infection Glyn Hewinson

  2. Experimental Challenge vs ‘Natural’ (transmission blocking) models of infection Experimental Challenge • Un-natural challenge • High dose to ensure all controls are infected. • One dose at one time point • Challenge organism grown in culture • Readout: Reduction in disease burden (cfu, pathology) ’Natural’ Challenge • Dose may vary over time – natural route • Constant challenge over months/years often from multiple sources • Challenge organism transmitted following growth in host. • Potential to study herd immunity • Readout: Blocking of naturally acquired infection (and reduction in disease burden).

  3. BCG Danish vaccination experiments in cattle after intra-tracheal infection conducted at AHVLA/IAH over the last 6 years: Duration of immunity? N N N N 1-year DOI 2-years DOI 1 year M. bovis BCG 2 years M. bovis BCG

  4. Ethiopian ‘Natural transmission model’ • Evaluation of the efficacy of BCG in bovine neonates under natural transmission in Ethiopia • Vaccinated and control calves in contact with infected cows (12 - 22 months)

  5. BCG vaccination experiment in Ethiopia (2007-09) • Study site: High-intensity farm, central highlands west of Addis Ababa (Oromiya Province) • Vaccine, dose and route: BCG SSI (freeze-dried), 106 CFU, subcutaneous • Breed of donors and vaccinates: Pure-bred Holsteins • Neonatal vaccination (<3 weeks of age) • Type of challenge: In-contact with reactor animals, standard farming/husbandry conditions • Exposure to reactors: about 3 months post-vaccination • In-contact period: 10 – 22 months • Read-out: Gross pathology/M. bovis culture 5

  6. ‘Natural Transmission’ study Findings • 69 % of vaccinated animals were fully protected from infection having no signs of visible lesions and being culture-negative compared to 21 % of cattle in the control group. (Ameni et al. 2010). • When the condemnation rate at meat inspection was used as additional read-out system, 73 % of the control cows would have been condemned compared to 23 % of the vaccinated group. • This study suggested that duration of immunity may be longer in the field than the minimum of one year demonstrated through the experimental vaccination and challenge experiments.

  7. ‘Natural transmission model’ • Repeat evaluation of the efficacy of BCG in bovine neonates under natural transmission in Ethiopia on-going - Gates Foundation and DFID funded • Vaccinated and control calves introduced into dairy farm with high prevalence of BTB experiment ongoing. • Establish reproducible methodology and skills/capacity/capability to test other vaccine candidates. • Large scale field trials are being planned for GB.

  8. Badgers were not killed for post-mortem confirmation of TB; relied on three ‘live’ tests • 2010: Significant reduction (of 74%) in new incidence of antibody positive results at social group level as a result of vaccination • Consistent with protective effect of vaccination, as antibody production positively correlated with extent & severity of TB in badgers • 2012: Further analysis of study data identifies a direct beneficial effect of vaccination in individual badgers and an indirect protective effect in unvaccinated cubs (‘herd effect’) • 54% reduction (Odds ratio = 0.46) in incidence of a ‘triple test’ result • Risk of unvaccinated badger cubs testing positive to TB decreased significantly as the proportion of vaccinated individuals in their social group increased (Odds ratio = 0.08) • When more than a third of their social group had been vaccinated, the risk to unvaccinated cubs was reduced by 79% (Odds ratio = 0.21) • But, blood tests are not an absolute indicator of protection from disease so the results cannot tell us the degree of vaccine efficacy

  9. Acknowledgements AHVLA Martin Vordermeier Adam Wheeler Gareth Jones Mick Coad Derek Clifford Bernardo Villarreal-Ramos Bagwati Upadhyay Stefan Berg AHRI/IOB Gobena Ameni Abraham Aseffa NIMR Douglas Young Funding: Wellcome Trust, Gates Foundation, DIFD • Funding: • Defra • FERA: • Woodchester Field Team • Stats Team • AHVLA • Badger Research Team led by Mark Chambers • TB Diagnostic Laboratory • Pathology Department • Animal Services Unit

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