Research roadmap for contagious bovine pleuropneumonia (CBPP) vaccine development

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Rationally attenuated candidates

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Dependencies

8 Attenuated organisms

Next steps

1 Vaccine

Rationally attenuated candidates

Research Question

Live attenuated organism-based vaccines can provoke robust and long duration of immunity against disease.

Research Gaps and Challenges

Need to improve the control of CBPP using existing LAVs as it is unlikely that effort will be put into identifying new “natural” LAVs.
Issues such as need for a cold chain, short duration of immunity after a single vaccine dose, the incidence of side effects, access to vaccine, diluent composition and short shelf life after reconstitution and policies restrict the routine use of current LAVs.
Lack of in vitro tests that correlate/associate with different clinical manifestations of and immunity to CBPP.

Solution Routes

Resolve conflicting data on the quality, safety and use of T1/44 and T1sr
Develop disease related metrics that do not rely on postmortem data to assess vaccine efficacy.
Establish if there is a dose response in cattle breeds between route of immunization and interval between primary and booster vaccinations to obtain the best safety, efficacy and duration of immunity in different age groups of cattle.
Field evaluation of improved vaccination regimens and protocols.
Develop tests to allow differentiation of infected from vaccinated animals (DIVA).
Develop biomarkers for improved diagnosis of different clinical phases of CBPP.
Increase quality and quantity of immune response in the lungs.

Dependencies

Agreement on whether to use T1/44 or T1sr would simplify developing solution routes.
Need to increase vaccine production as it is estimated that only 16% of the vaccine required to vaccinate 80% of Africa’s 370 million at-risk cattle population was produced in 2022.
Harmonize regional, national, and continental wide vaccination policies and campaigns for better manufacture and delivery of LAVs.
Improve fragmented veterinary services and vaccine supply chain.
Incentivize use of GMP and AU-PANVAC certified vaccines and pharmacovigilance in disease control.

State Of the Art

Several attenuated Mmm strains have been isolated by passage but only T1/44 and T1sr are recommended by WOAH for vaccination.
Deployment of a bivalent CBPP-rinderpest vaccine led to control of CBPP in many countries, but regular CBPP vaccination was discontinued after the rinderpest eradication campaign leading to re-emergence of CBPP.
Sustained vaccination can result in control of CBPP; modelling data suggest need >80% vaccine coverage and booster doses.
T1/44 and T1sr are produced as freeze-dried vaccines by seven certified laboratories in Africa.
The minimal required titre is 10⁷ mycoplasmas per vaccine dose, but higher titres of at least 10⁸ are recommended.
T1/44 induces higher efficacy and a longer duration of immunity than T1sr.
Vaccine efficacy for T1/44 ranges from ~40-60% after a single dose given subcutaneously in the neck and efficacy levels increase on boosting.
“Willems reaction” can occur in ~10% of animals 2 to 3 weeks post vaccination with T1/44 but is not evident on boosting. The percentage of reactors varies greatly from one region to another.
Recommended to vaccinate animals over 6 months old except in case of a severe outbreak, as calves less than 3 months can develop arthritis or valvular heart disease.
T1/44 was attenuated by passaging a mild field strain 44 times in embryonated eggs. T1/44 retains low level of virulence.
Strain T1sr is a direct derivative of T1/44, adapted to streptomycin resistance by four serial passages in growth medium with increasing concentrations of streptomycin. T1sr has no residual virulence.

Contavax (KEVAVAPI): Freeze-dried vaccine. Stored at -20°C the shelf life is 2 years. At 2°C to 8°C the shelf life is one month. Once the vaccine has been reconstituted, it must be kept cool and used immediately. 50-100 dose pks with diluent.
BoviVax (MCI): Freeze-dried vaccine. No shelf-life data. Once the vaccine has been reconstituted, it must be kept cool and used immediately. 50-100 dose pks with diluent.