An overview of the sand fly salivary proteins in vaccine development against leishmaniases
Abstract
Leishmaniases are a group of vector-borne parasitic diseases transmitted through the infected sand flies. Leishmania parasites are inoculated into the host skin along with sand fly saliva. The sand fly saliva consists of biologically active molecules with anticoagulant, anti-inflammatory, and immunomodulatory properties. Such properties help the parasite circumvent the host's immune responses. The salivary compounds support the survival and multiplication of the parasite and facilitate the disease progression. It is documented that frequent exposure to uninfected sand fly bites produces neutralizing antibodies against specific salivary proteins and further activates the cellular mechanisms to prevent the establishment of the disease. The immune responses due to sand fly saliva are highly specific and depend on the composition of the salivary molecules. Hence, thorough knowledge of these compounds in different sand fly species and information about their antigenicity are paramount to designing an effective vaccine. Herein, we review the composition of the sand fly saliva, immunomodulatory properties of some of its components, immune responses to its proteins, and potential vaccine candidates against leishmaniases.
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2. Kamhawi S. The biological and immunomodulatory properties of sand fly saliva and its role in the establishment of Leishmania infections. Microbes Infect 2000; 2: 1765-1773.
3. Oliveira F, De Carvalho AM, De Oliveira CI. Sand-fly saliva-Leishmania-man: the trigger trio. Front Immunol 2013; 4: 375.
4. Rohoušová I, Volf P. Sand fly saliva: effects on host immune response and Leishmania transmission. Folia Parasitol (Praha) 2006; 53: 161-171.
5. Assumpção TCF, Ma D, Schwarz A, Reiter K, Santana JM, Andersen JF, et al. Salivary antigen-5/CAP family members are Cu2+-dependent antioxidant enzymes that scavenge O2— and inhibit collagen-induced platelet aggregation and neutrophil oxidative burst. J Biol Chem 2013; 288: 14341-14361.
6. Kamhawi S, Belkaid Y, Modi G, Rowton E, Sacks D. Protection against cutaneous leishmaniasis resulting from bites of uninfected sand flies. Science 2000; 290: 1351-1354.
7. Gomes R, Teixeira C, Teixeira MJ, Oliveira F, Menezes MJ, Silva C, et al. Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model. Proc Natl Acad Sci U S A 2008; 105: 7845-7850.
8. Sima M, Ferencova B, Warburg A, Rohousova I, Volf P. Recombinant salivary proteins of Phlebotomus orientalis are suitable antigens to measure exposure of domestic animals to sand fly bites. PLoS Negl Trop Dis 2016; 10(3): e0004553.
9. Kostalova T, Lestinova T, Maia C, Sumova P, Vlkova M, Willen L, et al. The recombinant protein r SP03B is a valid antigen for screening dog exposure to P hlebotomus perniciosus across foci of canine leishmaniasis. Med Vet Entomol 2017; 31: 88-93.
10. Lerner EA, Ribeiro JM, Nelson RJ, Lerner MR. Isolation of maxadilan, a potent vasodilatory peptide from the salivary glands of the sand fly Lutzomyia longipalpis. J Biol Chem 1991; 266: 11234-11236.
11. Hamasaki R, Kato H, Terayama Y, Iwata H, Valenzuela JG. Functional characterization of a salivary apyrase from the sand fly, Phlebotomus duboscqi, a vector of Leishmania major. J Insect Physiol 2009; 55: 1044-1049.
12. Chagas AC, Oliveira F, Debrabant A, Valenzuela JG, Ribeiro JM, Calvo E. Lundep, a sand fly salivary endonuclease increases Leishmania parasite survival in neutrophils and inhibits XIIa contact activation in human plasma. PLoS Pathog 2014; 10(2): e1003923.
13. Kato H, Gomez EA, Fujita M, Ishimaru Y, Uezato H, Mimori T, et al. Ayadualin, a novel RGD peptide with dual antihemostatic activities from the sand fly Lutzomyia ayacuchensis, a vector of Andean-type cutaneous leishmaniasis. Biochimie 2015; 112: 49-56.
14. Jablonka W, Kim IH, Alvarenga PH, Valenzuela JG, Ribeiro JMC, Andersen JF. Functional and structural similarities of D7 proteins in the independently-evolved salivary secretions of sand flies and mosquitoes. Sci Rep 2019; 9: 5340.
15. Lestinova T, Rohousova I, Sima M, De Oliveira CI, Volf P. Insights into the sand fly saliva: Blood-feeding and immune interactions between sand flies, hosts, and Leishmania. PLoS Negl Trop Dis 2017; 11(7): e0005600.
16. Alvarenga PH, Xu X, Oliveira F, Chagas AC, Nascimento CR, Francischetti IMB, et al. Novel family of insect salivary inhibitors blocks contact pathway activation by binding to polyphosphate, heparin, and dextran sulfate. Arterioscler Thromb Vasc Biol 2013; 33: 2759-2770.
17. Abdeladhim M, Coutinho-Abreu IV, Townsend S, Pasos-Pinto S, Sanchez L, Rasouli M, et al. Molecular diversity between salivary proteins from New World and Old World sand flies with emphasis on Bichromomyia olmeca, the sand fly vector of Leishmania mexicana in Mesoamerica. PLoS Negl Trop Dis 2016; 10(7): e0004771.
18. Ribeiro JM, Katz O, Pannell LK, Waitumbi J, Warburg A. Salivary glands of the sand fly Phlebotomus papatasi contain pharmacologically active amounts of adenosine and 5′-AMP. J Exp Biol 1999; 202: 1551-1559.
19. Valenzuela JG, Garfield M, Rowton ED, Pham VM. Identification of the most abundant secreted proteins from the salivary glands of the sand fly Lutzomyia longipalpis, vector of Leishmania chagasi. J Exp Biol 2004; 207: 3717-3729.
20. Collin N, Assumpção TCF, Mizurini DM, Gilmore DC, Dutra-Oliveira A, Kotsyfakis M, et al. Lufaxin, a novel factor Xa inhibitor from the salivary gland of the sand fly Lutzomyia longipalpis blocks protease-activated receptor 2 activation and inhibits inflammation and thrombosis in vivo. Arterioscler Thromb Vasc Biol 2012; 32: 2185-2198.
21. Volfova V, Hostomska J, Cerny M, Votypka J, Volf P. Hyaluronidase of bloodsucking insects and its enhancing effect on leishmania infection in mice. PLoS Negl Trop Dis 2008; 2(9): e294.
22. Teixeira C, Gomes R, Collin N, Reynoso D, Jochim R, Oliveira F, et al. Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America. PLoS Negl Trop Dis 2010; 4(3): e638.
23. Xu X, Oliveira F, Chang BW, Collin N, Gomes R, Teixeira C, et al. Structure and function of a “yellow” protein from saliva of the sand fly Lutzomyia longipalpis that confers protective immunity against Leishmania major infection. J Biol Chem 2011; 286: 32383-32393.
24. Spitzova T, Sumova P, Volfova V, Polanska N, Poctova L, Volf P. Interactions between host biogenic amines and sand fly salivary yellow-related proteins. Parasit Vectors 2020; 13: 237.
25. Soares MB, Titus RG, Shoemaker CB, David JR, Bozza M. The vasoactive peptide maxadilan from sand fly saliva inhibits TNF-α and induces IL-6 by mouse macrophages through interaction with the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor. J Immunol 1998; 160: 1811-1816.
26. Sumova P, Polanska N, Lestinova T, Spitzova T, Kalouskova B, Vanek O, et al. Phlebotomus perniciosus recombinant salivary proteins polarize murine macrophages toward the anti-inflammatory phenotype. Front Cell Infect Microbiol 2020; 10: 427.
27. Ferreira VP, Fazito Vale V, Pangburn MK, Abdeladhim M, Mendes-Sousa AF, Coutinho-Abreu IV, et al. SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis. Sci Rep 2016; 6: 19300.
28. Guimaraes-Costa AB, Shannon JP, Waclawiak I, Oliveira J, Meneses C, De Castro W, et al. A sand fly salivary protein acts as a neutrophil chemoattractant. Nat Commun 2021; 12: 3213.
29. Charlab R, Rowton ED, Ribeiro JM. The salivary adenosine deaminase from the sand fly Lutzomyia longipalpis. Exp Parasitol 2000; 95: 45-53.
30. Quinnell RJ, Soremekun S, Bates PA, Rogers ME, Garcez LM, Courtenay O. Antibody response to sand fly saliva is a marker of transmission intensity but not disease progression in dogs naturally infected with Leishmania infantum. Parasit Vectors 2018; 11: 7.
31. Souza AP, Andrade BB, Aquino D, Entringer P, Miranda JC, Alcantara R, et al. Using recombinant proteins from Lutzomyia longipalpis saliva to estimate human vector exposure in visceral Leishmaniasis endemic areas. PLoS Negl Trop Dis 2010; 4(3): e649.
32. Soares BR, Souza APA, Prates DB, De Oliveira CI, Barral-Netto M, Miranda JC, et al. Seroconversion of sentinel chickens as a biomarker for monitoring exposure to visceral leishmaniasis. Sci Rep 2013; 3: 2352.
33. Martín-Martín I, Molina R, Rohoušová I, Drahota J, Volf P, Jiménez M. High levels of anti-Phlebotomus perniciosus saliva antibodies in different vertebrate hosts from the re-emerging leishmaniosis focus in Madrid, Spain. Vet Parasitol 2014; 202: 207-216.
34. Drahota J, Martin-Martin I, Sumova P, Rohousova I, Jimenez M, Molina R, et al. Recombinant antigens from Phlebotomus perniciosus saliva as markers of canine exposure to visceral leishmaniases vector. PLoS Negl Trop Dis 2014; 8(1): e2597.
35. Kostalova T, Lestinova T, Sumova P, Vlkova M, Rohousova I, Berriatua E, et al. Canine antibodies against salivary recombinant proteins of Phlebotomus perniciosus: A longitudinal study in an endemic focus of canine leishmaniasis. PLoS Negl Trop Dis 2015; 9(6): e0003855.
36. Carvalho AM, Fukutani KF, Sharma R, Curvelo RP, Miranda JC, Barral A, et al. Seroconversion to Lutzomyia intermedia LinB-13 as a biomarker for developing cutaneous leishmaniasis. Sci Rep 2017; 7: 3149.
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| Files | ||
| Issue | Vol 14 No 6 (2022) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v14i6.11253 | |
| Keywords | ||
| Sand fly; Salivary proteins; Leishmania; Vaccine; Immunity | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Fayaz S, Bahrami F, Parvizi P, Fard-Esfahani P, Ajdary S. An overview of the sand fly salivary proteins in vaccine development against leishmaniases. Iran J Microbiol. 2022;14(6):792-801.
