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Design of Mycoplasma vaccines employing synthetic biology tools

Elise Schieck, Paul Ssajjakambwe, Cecilia Muriuki, Joerg Jores

ILRI BioSciences Day, Nairobi, 27 November 2013

Design of Mycoplasma vaccines employing synthetic biology tools

• Introduction• Why is this research important for ILRI-a vaccine against one of the most important livestock diseases in Africa is important to ILRI-This research is putting ILRI on the map of institutes with world-class cutting edge bioscience• Who are the recipients of the outcomes-Stakeholders in the livestock sector: smallholder farmers, pastoralists, animal health workers, milk-drinkers and beef-eaters in the countries affected• How will it change their lives-farmers will generate more profit, nutrition will improve

The problem: its significance

• What is the state of the problem?-CBPP is widespread in Africa, and the affected region is still expanding.• How will this project change the outcomes?-An effective vaccine will be included in control measures against the disease, including possible eradication• What are the links to ILRI’s strategy (SLOs and Strategic

Outcomes)?:-Reduce rural poverty, Improve food security, Improve nutrition and health, Sustainably manage natural resources

Scientific approach

• Genome transplantation• Allows seamless deletions• GMO vaccine possible• Kill-switch or temperature sensitive • Allows identification of virulence genes, a step to rational subunit vaccine design

Scientific approach

• Targeting polysaccharide capsule

• Capsule hides the bacteria from the immune system• Sugars are very inefficient immunogens• Immunity to CBPP is very shortlived

We are deleting genes involved in capsule biosynthesis

Cell membrane

Nuclear material

Capsule

Results-1

• Deleting genes involved in capsule biosynthesis

• 3 genes deleted:

Mmc GM12genome

1,089,202bp

glf

bgl

glycosyltransferase

Results-2

• Backtransplantation of altered genomes

• Mycoplasma mutants:• glf deletion mutant

glf mutants wildtype

Conclusions and discussion points

• We have introduced genome transplantation to ILRI and Africa

• Will substantially accelerate CBPP research towards a better vaccine

• First mutants have been made• Next step:• Do these mutations have an effect on virulence? If so

a glycoconjugated vaccine is a promising and novel approach to control Mycoplasma related diseases

Where to from now?

• How will it contribute to the four CGIAR System Level Outcomes (Reduce poverty, improve nutrition, improve food security and Sustainably manage natural resources) and link with CRP/value chains?

CRPs: 4.3 and 3.7Value chains: dairy and beef, small ruminants

• Our Partners:JCVI, INRA, FLI, Alberta Glycomics Centre, UoB, TiHo

General discussion

• Funding:-Approved BMZ grant on development of CBPP vaccines and diagnostics (German Federal Ministry for Economic Cooperation and Development)-BMZ Postdoc (myself)-NSF (US National Science Foundation)

• Resource mobilization• What support do you expect from ILRI and the

BioScience Directorate?

The presentation has a Creative Commons licence. You are free to re-use or distribute this work, provided credit is given to ILRI.

better lives through livestock

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