scholarly journals Immunity to Sand Fly Salivary Protein LJM11 Modulates Host Response to Vector-Transmitted Leishmania Conferring Ulcer-Free Protection

2012 ◽  
Vol 132 (12) ◽  
pp. 2735-2743 ◽  
Author(s):  
Regis Gomes ◽  
Fabiano Oliveira ◽  
Clarissa Teixeira ◽  
Claudio Meneses ◽  
Dana C. Gilmore ◽  
...  
Keyword(s):  
Host Response ◽  
Salivary Protein ◽  
Sand Fly

scholarly journals A sand fly salivary protein acts as a neutrophil chemoattractant

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anderson B. Guimaraes-Costa ◽  
John P. Shannon ◽  
Ingrid Waclawiak ◽  
Jullyanna Oliveira ◽  
Claudio Meneses ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Calcium Influx ◽  
Parasite Burden ◽  
Salivary Protein ◽  
Sand Fly ◽  
Human Neutrophils ◽  
Chemotactic Protein ◽  
The Impact

AbstractApart from bacterial formyl peptides or viral chemokine mimicry, a non-vertebrate or insect protein that directly attracts mammalian innate cells such as neutrophils has not been molecularly characterized. Here, we show that members of sand fly yellow salivary proteins induce in vitro chemotaxis of mouse, canine and human neutrophils in transwell migration or EZ-TAXIScan assays. We demonstrate murine neutrophil recruitment in vivo using flow cytometry and two-photon intravital microscopy in Lysozyme-M-eGFP transgenic mice. We establish that the structure of this ~ 45 kDa neutrophil chemotactic protein does not resemble that of known chemokines. This chemoattractant acts through a G-protein-coupled receptor and is dependent on calcium influx. Of significance, this chemoattractant protein enhances lesion pathology (P < 0.0001) and increases parasite burden (P < 0.001) in mice upon co-injection with Leishmania parasites, underlining the impact of the sand fly salivary yellow proteins on disease outcome. These findings show that some arthropod vector-derived factors, such as this chemotactic salivary protein, activate rather than inhibit the host innate immune response, and that pathogens take advantage of these inflammatory responses to establish in the host.

LJM19, a salivary protein from the sand fly vector that transmits leishmaniasis, is a novel inhibitor of the classical pathway of complement

Immunobiology ◽  
2012 ◽  
Vol 217 (11) ◽  
pp. 1182
Author(s):  
Viviana P. Ferreira ◽  
Gurpanna Saggu ◽  
Marcos H. Pereira ◽  
Ricardo N. Araújo ◽  
Vladimir F. Vale ◽  
...  
Keyword(s):  
Salivary Protein ◽  
Sand Fly ◽  
Classical Pathway

scholarly journals A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates

2015 ◽  
Vol 7 (290) ◽  
pp. 290ra90-290ra90 ◽  
Author(s):  
Fabiano Oliveira ◽  
Edgar Rowton ◽  
Hamide Aslan ◽  
Regis Gomes ◽  
Philip A. Castrovinci ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Nonhuman Primates ◽  
Mononuclear Cells ◽  
Rhesus Macaques ◽  
Parasite Burden ◽  
Salivary Protein ◽  
Sand Fly ◽  
Protein Vaccine ◽  
Peripheral Blood Mononuclear ◽  
Phlebotomus Duboscqi

Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to salivary proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman primates (NHP) exposed to Phlebotomus duboscqi uninfected sand fly bites or immunized with salivary protein PdSP15 are protected against cutaneous leishmaniasis initiated by infected bites. Uninfected sand fly–exposed and 7 of 10 PdSP15-immunized rhesus macaques displayed a significant reduction in disease and parasite burden compared to controls. Protection correlated to the early appearance of Leishmania-specific CD4+IFN-γ+ lymphocytes, suggesting that immunity to saliva or PdSP15 augments the host immune response to the parasites while maintaining minimal pathology. Notably, the 30% unprotected PdSP15-immunized NHP developed neither immunity to PdSP15 nor an accelerated Leishmania-specific immunity. Sera and peripheral blood mononuclear cells from individuals naturally exposed to P. duboscqi bites recognized PdSP15, demonstrating its immunogenicity in humans. PdSP15 sequence and structure show no homology to mammalian proteins, further demonstrating its potential as a component of a vaccine for human leishmaniasis.

scholarly journals Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model

2008 ◽  
Vol 105 (22) ◽  
pp. 7845-7850 ◽  
Author(s):  
R. Gomes ◽  
C. Teixeira ◽  
M. J. Teixeira ◽  
F. Oliveira ◽  
M. J. Menezes ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Fatal Outcome ◽  
Salivary Protein ◽  
Sand Fly ◽  
Hamster Model

scholarly journals The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B

2017 ◽  
Vol 8 ◽  
Author(s):  
Antonio F. Mendes-Sousa ◽  
Vladimir Fazito do Vale ◽  
Naylene C. S. Silva ◽  
Anderson B. Guimaraes-Costa ◽  
Marcos H. Pereira ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Salivary Protein ◽  
Sand Fly ◽  
Direct Binding ◽  
Alternative Pathway Of Complement

scholarly journals Protective Efficacy in a Hamster Model of a Multivalent Vaccine for Human Visceral Leishmaniasis (MuLeVaClin) Consisting of the KMP11, LEISH-F3+, and LJL143 Antigens in Virosomes, Plus GLA-SE Adjuvant

2021 ◽  
Vol 9 (11) ◽  
pp. 2253
Author(s):  
Laura Fernández ◽  
Jose Carlos Solana ◽  
Carmen Sánchez ◽  
Mª Ángeles Jiménez ◽  
Jose M. Requena ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Process Development ◽  
Protective Efficacy ◽  
Humoral Response ◽  
Cost Effective ◽  
Salivary Protein ◽  
Sand Fly ◽  
Vaccine Formulation ◽  
Hamster Model ◽  
Nucleoside Hydrolase

Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, fatal if untreated. Vaccination is the most cost-effective approach to disease control; however, to date, no vaccines against human VL have been made available. This work examines the efficacy of a novel vaccine consisting of the Leishmania membrane protein KMP11, LEISH-F3+ (a recombinant fusion protein, composed of epitopes of the parasite proteins nucleoside hydrolase, sterol-24-c-methyltransferase, and cysteine protease B), and the sand fly salivary protein LJL143, in two dose ratios. The inclusion of the TLR4 agonist GLA-SE as an adjuvant, and the use of virosomes (VS) as a delivery system, are also examined. In a hamster model of VL, the vaccine elicited antigen-specific immune responses prior to infection with Leishmania infantum. Of note, the responses were greater when higher doses of KMP11 and LEISH-F3+ proteins were administered along with the GLA-SE adjuvant and/or when delivered within VS. Remarkably, hamsters immunized with the complete combination (i.e., all antigens in VS + GLA-SE) showed significantly lower parasite burdens in the spleen compared to those in control animals. This protection was underpinned by a more intense, specific humoral response against the KMP11, LEISH-F3+, and LJL143 antigens in vaccinated animals, but a significantly less intense antibody response to the pool of soluble Leishmania antigens (SLA). Overall, these results indicate that this innovative vaccine formulation confers protection against L. infantum infection, supporting the advancement of the vaccine formulation into process development and manufacturing and the conduction of toxicity studies towards future phase I human clinical trials.

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