Eranet LEAP Agri - Eranet LEAP Agri 2018

Multivalent inactivated vaccine against heartwater in Africa – MuVHA

Multivalent inactivated Vaccine against Heartwater in Africa

Heartwater (HW), transmitted by Amblyomma ticks, is a tropical fatal disease of ruminants, caused by Ehrlichia ruminantium (ER) and constitute a major threat to livestock production in Africa. An efficient, cost-effective and safe vaccine against HW to alleviate poverty of smallholder farmers, particularly women and children, and contribute to a sustainable agriculture in Africa is urgently needed.

Develop an efficient inactivated vaccine against Heartwater, adapted to a specific geographical region, easy to produce by regional manufacturers and easy to use by vet services and farmers.

The project aims at providing an efficient multivalent inactivated vaccine against heartwater to improve animal health of ruminants, particularly small ruminants that are important for local economy in Africa. The development, acceptance and use of this new vaccine will not only participate in improving knowledge in Animal sciences and in targeting disease control, but will also bring new insights in sustainable food security as well as rural development and agricultural economy.<br />Our consortium propose to tackle the drawback of antigenic diversity of Ehrlichia ruminantium (ER, etiologic agent of heartwater) strains, by including a cocktail of strains of different regional genotypes newly isolated within the project. Also, process of production of improved vaccine formulations at industrial level will be available at the end of the project.<br />The specific objectives are: (i) evaluate the efficacy of the inactivated regional<br />cocktail vaccine in Western and Southern Africa, (ii) identify and validate<br />biomarkers associated to protection and/or vaccination and (iii) design a rapid test to differentiate vaccinated/protected animals from naïve animals.<br />The current project will also allow increasing regional heartwater diagnostic and research capacities. Special efforts will be done to share the research products with stakeholders such as farmers and local vaccine manufacturers.

- Strengthened capacity of regional partners for Ehrlichia ruminantium diagnostic and research through the creation of an experts network shared between South and West Africa and Europe
- Transdisciplinary communication strategy and capacity building (scientists and students, farmers associations, regional vaccine manufacturers, policy makers, …) to achieve both scientific and technical knowledge on the vaccine production and adoption of its use
- Definition of Ehrlichia ruminantium current genetic diversity in West and South Africa and isolation of up to date Ehrlichia ruminantium strains to be targeted by the vaccine
- Establishment of standardised protocol and conditions for production of the emulsified vaccine and an efficient quality control protocol, with scale-up consideration for further industrial production by regional manufacturers
- An efficient improved (geographically adapted) inactivated multivalent vaccine against Heartwater
- Identification of biomarkers associated with protective immune responses for vaccine efficacy follow-up

The current progresses of the project are: (i) the organization of meetings with stakeholder on livestock infectious diseases and the start of socio-economic studies to aid decision making for vaccine development and establish preferences of farmers and potential impact of vaccine, (ii) the sampling of Amblyomma ticks for Ehrlichia ruminantium current main regional strains isolation and evaluation of Ehrlichia ruminantium diversity in Western and Southern Africa, (iii) capacity building with the training of students and technical staff and (iv) the development of a quality control protocol for vaccine production allowing the dose to be adapted according to the Ehrlichia ruminantium strain produced.

The last challenge will be to prove the effectiveness of our multivalent vaccine
cocktails through its use in the field, then at the end of the project, to find new funding to support the transfer of production technology and quality control to partners (local vaccine manufacturers) and the deployment and monitoring of the vaccine in target populations.

4 publications are in preparation:
- Development of a goat micro-array (V Rodrigues, Y Sun, E Loire, P Holzmuller, L Manso-Silvan)

- The perception and the means of controlling Heartwater in ruminants by breeders: a socio-economics consideration. (A Biguezoton, P Chaminuka, A Kaboré)

- New adjuvant for inactivated vaccine against heartwater (V Rodrigues, M Jean Marie Flore, Damien Meyer, E Albina, N Vachiery, P Holzmuller, L Manso Silvan)

- Use of proteomics for quality control of multivalent vaccine against Heartwater (P Holzmuller, L Mounier, B Fernandez, K El Koulali, M Séveno, N Vachiery, V Rodrigues)

Heartwater, caused by Ehrlichia ruminantium (ER) , constitute a major threat to ruminant production in Africa, affecting mainly small ruminants. Although a commercial vaccine is available, it presents so many drawbacks that its use is limited. An efficient, cost-effective and safe vaccine against
heartwater to alleviate poverty of smallholder farmers and contribute to a sustainable agriculture in Africa is needed. The inactivated vaccine constitutes the most advanced experimental vaccine against heartwater. The main drawback of any experimental vaccine is the high antigenic diversity of ER strains, limiting its efficacy under field conditions. Our consortium composed of 2 European and 4 African partners propose to tackle this limitation by including a cocktail of strains of different regional genotypes newly isolated within the project. First, the genetic diversity of ER strains from Benin, Burkina Faso, Niger and South Africa, will be assessed during the first two years of the project allowing a follow-up and identification of predominant strain variations circulating over time. New ER strains from different genotypes will be isolated and included in two regional multivalent vaccines. Finally, the efficacy of the inactivated vaccine will be evaluated in field conditions, tested in Burkina Faso and South Africa, respectively, with a new promising oil adjuvant and with a single injection and protection-associated biomarkers will be identify to minimize the need for challenges after any new vaccine trials. Process of production of improved vaccine formulations at industrial level and efficient quality controls will be available at the end of the project. Current project will also allow increasing regional heartwater diagnostic and research capacities. Special efforts will be done to share the research products with stakeholders and end-users such as farmers and local manufacturers.

Project coordination

Philippe Holzmuller (Animal, Santé, Territoires, Risques et Ecosystèmes)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partnership

ASTRE Animal, Santé, Territoires, Risques et Ecosystèmes
CIRDES
IBET - Instituto de Biologia Experimental e Technologica
INERA - Institut de l Environnement et de Recherches Agricoles

Help of the ANR 421,889 euros
Beginning and duration of the scientific project: August 2018 - 36 Months

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