Contagious bovine pleuropneumonia: identification of candidate vaccine molecules through inhibition of pathogen-host cell interaction with monoclonal antibodies

Contagious bovine Pleuropneumonia (CBPP) is a severe respiratory disease of cattle that causes economic loses of up to 40 million Euros annually in sub-Saharan Africa. The preferred method of control is vaccination however the currently available vaccine confers insufficient and short term immunity hence there is need to develop a better vaccine. The disease is caused by Mycoplasma mycoides subsp. mycoides (Mmm) a pathogen that belongs to a group of closely related pathogens, the M. mycoides cluster. Mmm only causes pneumonia in cattle and related species but not in sheep or goats, suggesting that there must be a specific interaction between bovine lung cells and Mmm. Calves younger than six months on the other hand do not develop pneumonia but rather arthritis and associated lameness. The aim of thesis is to assess the adherence of Mmm to host cells and to further identifiy Mmm specific monoclonal antibodies that block this binding. This is the first study to describe the adhesion process for Mmm. Our hypothesis is that prevention of binding between Mmm and bovine lung epithelial cells in vivo will prevent severe disease. The identification of the Mycoplasma adhesin(s) that mediate this interaction could be candidate vaccine targets. The specific objectives of this study are to assess the manifestation of CBPP in 7 month old calves and to compare in- contact and intubation methods of infection, establish an indirect flow cytometry assay to measure Mycoplasma adherence to different host cells and produce a panel of Mmm- specific monoclonal antibodies, and select for mAbs that inhibit Mmm adherence to bovine lung epithelial cells; select carbohydrate substances with different functional groups and test their ability to inhibit Mmm cyto-adherence. The antigens to antibodies that inhibit adherence could be potential vaccine candidates