Immunization with LJM11 salivary protein protects against infection with Leishmania braziliensis in the presence of Lutzomyia longipalpis saliva

Abstract

Leishmania is transmitted in the presence of sand fly saliva. Protective immunity generated by saliva has encouraged identification of a vector salivary-based vaccine. Previous studies have shown that immunization with LJM11, a salivary protein from Lutzomyia longipalpis, is able to induce a Th1 immune response and protect mice against bites of Leishmania major-infected Lutzomyia longipalpis. Here, we further investigate if immunization with LJM11 recombinant protein is able to confer cross-protection against infection with Leishmania braziliensis associated with salivary gland sonicate (SGS) from Lutzomyia intermedia or Lu. longipalpis. Mice immunized with LJM11 protein exhibited an increased production of anti-LJM11 IgG, IgG1 and IgG2a and a DTH response characterized by an inflammatory infiltrate with the presence of CD4 IFN-γ T cells. LJM11-immunized mice were intradermally infected in the ear with L. braziliensis in the presence of Lu. longipalpis or Lu. intermedia SGS. A significant reduction of parasite numbers in the ear and lymph node in the group challenged with L. braziliensis plus Lu. longipalpis SGS was observed, but not when the challenge was performed with L. braziliensis plus Lu. intermedia SGS. A higher specific production of IFN-γ and absence of IL-10 by lymph node cells were only observed in LJM11 immunized mice after infection. After two weeks, a similar frequency of CD4 IFN-γ T cells was detected in LJM11 and BSA groups challenged with L. braziliensis plus Lu. longipalpis SGS, suggesting that early events possibly triggered by immunization are essential for protection against Leishmania infection. Our findings support the specificity of saliva-mediated immune responses and reinforce the importance of identifying cross-protective salivary antigens.

RNA-sequencing of the Nyssomyia neivai sialome: a sand fly-vector from a Brazilian endemic area for tegumentary leishmaniasis and pemphigus foliaceus

“…LJM17 from Lu. longipalpis elicited leishmanicidal Th1 cytokines in immunized dogs 74 , 75 , and LJM11 protected laboratory animals against L. (L.) infantum (Nicolle 1908), L. (L.) major, and L. (V.) braziliensis 70 , 76 , 77 .…”

Phlebotomus perniciosus Recombinant Salivary Proteins Polarize Murine Macrophages Toward the Anti-Inflammatory Phenotype

“…In general, sand fly salivary proteins in a recombinant form might be used to understand the possible function of their native counterparts. Importantly, if the recombinant proteins are tested as candidates for leishmaniasis vaccine (Collin et al, 2009 ; Gomes et al, 2012 ; Abbehusen et al, 2018 ; Cunha et al, 2018 ), their possible immunogenic nature should be also considered since it may negatively influence the vaccinated individuals (Reagan et al, 2012 ), e.g., by initiating an autoimmune disease in susceptible recipients (Qian et al, 2016 ). Thus, any vaccine candidate molecules should be thoroughly tested to validate their overall beneficial status for the host immunity.…”

Engineering a vector-based pan-Leishmania vaccine for humans: proof of principle

“…One of the most recently explored possibilities of “anti- Leishmania ” vaccines are the vector-based ones. An anti-vector-saliva immune response, elicited by exposure to uninfected sand fly bites, conferred protection against vector-transmitted cutaneous disease 13 , opening the door to testing defined sand fly-salivary proteins as vaccines that demonstrated effectiveness in the context of cutaneous 14 – 18 or visceral 19 disease. Protection is thought to be mediated by saliva-specific IFN-γ secretion by CD4 + T cells at the bite site, early after transmission, via the generation of a robust Th1 delayed-type hypersensitivity (DTH) reaction, that negatively (and indirectly) affects parasites’ establishment 20 .…”