Protective effect of Water bug saliva against M. ulcerans lesion development

Abstract

International audienceAt this day, no specific vaccine against Buruli ulcer is available. BCG vaccination has first been suggested to have incomplete but significant short-term protective effects. Subsequent studies have provided highly controversial results with some showing partial protection against M. ulcerans osteomyelitis. The only study that did not solely rely on BCG scar for assessing BCG vaccination status (a procedure that has been shown to be unreliable when BCG is given under the age of three months which is the case is most African countries), but used vaccine booklet examination, did not find any significant protective effect of routine BCG vaccination against Buruli ulcer. Vaccination based on mycobacterial antigens (Hsp65, Ag85A) showed a short delay in lesion development and borderline impact on bacterial loads. These results demonstrated that the most efficient vaccine for Buruli ulcer does not solely rely on the Mycobacterium alone but is a combination of bacilli- and vector-based molecules as already shown for other microbial agents such as Borrelia and Leishmania. Recently, we have demonstrated that repeated water bug bites free of M. ulcerans could protect against M. ulceransinduced lesions.&nbsp; To test whether vector salivary proteins can protect against M. ulcerans lesion, a mouse model was developed involving intradermal inoculation in the tail of 1000 bacilli together with Water bug salivary gland homogenate to mimic a potential natural transmission. Before M. ulcerans inoculation, mice were immunized by immunogenic salivary proteins purified by affinity chromatography. &nbsp;We showed that salivary proteins confer protection against the M. ulcerans lesion development in mouse model. Moreover, two candidate proteins (isolated form salivary gland homogenate) that are able to bound M. ulcerans surface, were identified and detected in saliva fluid. These proteins were detected in several water bugs families.&nbsp; This work reinforces the concept of using components of arthropod saliva in vaccine strategies against M. ulcerans lesions.</p

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