A Listeria monocytogenes-Based Vaccine That Secretes Sand Fly Salivary Protein LJM11 Confers Long-Term Protection against Vector-Transmitted Leishmania major

Abstract

c Cutaneous leishmaniasis is a sand fly-transmitted disease characterized by skin ulcers that carry significant scarring and social stigmatization. Over the past years, there has been cumulative evidence that immunity to specific sand fly salivary proteins confers a significant level of protection against leishmaniasis. In this study, we used an attenuated strain of Listeria monocytogenes as a vaccine expression system for LJM11, a sand fly salivary protein identified as a good vaccine candidate. We observed that mice were best protected against an intradermal needle challenge with Leishmania major and sand fly saliva when vaccinated intravenously. However, this protection was short-lived. Importantly, groups of vaccinated mice were protected long term when challenged with infected sand flies. Protection correlated with smaller lesion size, fewer scars, and better parasite control be-

Phlebotomus papatasi Yellow-Related and Apyrase Salivary Proteins Are Candidates for Vaccination against Human Cutaneous Leishmaniasis

“…The efficacy of the “yellow proteins” in conferring protection against leishmaniasis has been well documented in the New World. In fact, the protective effect of LJM11 was demonstrated in mice infected with L. major (Abi Abdallah et al, 2014; Gomes et al, 2012). LJM11 induced a systemic Th1 immunity and a strong local delayed- type hypersensitivity reaction that correlated with protection (Abi Abdallah et al, 2014).…”

“…In fact, the protective effect of LJM11 was demonstrated in mice infected with L. major (Abi Abdallah et al, 2014; Gomes et al, 2012). LJM11 induced a systemic Th1 immunity and a strong local delayed- type hypersensitivity reaction that correlated with protection (Abi Abdallah et al, 2014). Moreover, immunization of dogs with LJM17 induced a strong cellular and humoral immunity mediated by Th1 lymphocytes (Collin et al, 2009).…”

TetR‐dependent gene regulation in intracellular Listeria monocytogenes demonstrates the spatiotemporal surface distribution of ActA

“…A recent and very interesting research area are the attempts to employ L. monocytogenes as a model organism for development of live attenuated vaccines for human applications (Le et al, 2012;Guirnalda et al, 2012;Abi Abdallah et al, 2014;Lizotte et al, 2014;Yang et al, 2014;Miller et al, 2015). This is a challenging task, because specially adapted, attenuated pathogens need to be able to persist intracellularly and express recombinant antigens for immune recognition, yet without negatively affecting the host organism.…”

Some Good and Some Bad: Sand Fly Salivary Proteins in the Control of Leishmaniasis and in Autoimmunity

“…longipalpis, LJM-19 protected hamsters from fatal VL caused by L. infantum (Gomes et al, 2008) as well as in the context of cutaneous disease caused by Leishmania braziliensis (Tavares et al, 2011). The LJM-11 protein (from Lu.longipalpis) attenuated CL caused by L. major (and L. braziliensis) in mice (Xu et al, 2011) (Abi Abdallah et al, 2014Cunha et al, 2018), as did LJL-14 (Cecilio et al, 2020). Notably, LJL-143 and LJM-17 were proposed as good vaccine candidates against canine Leishmaniasis caused by L. infantum, although an in vivo protective phenotype is yet to be demonstrated (Collin et al, 2009;Abbehusen et al, 2018).…”