Volume 70, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


The salivary protein maxadilan (MAX) is a vasodilator and immunomodulator from the sand fly vector of the protozoan parasite . Vaccinating BALB/c mice with sand fly salivary gland extracts or with MAX protects the host against infection. Because of the potential use of MAX in an anti- vaccine, we characterized the vertebrate host IgG response to MAX in the present study. Our immunochemical analysis indicated that antibodies to MAX were detected in BALB/c mice, as well as in pigs and humans, from a area in Nicaragua endemic for . Previous studies demonstrate that the MAX protein is polymorphic on the amino acid level. Our findings suggested that naturally occurring MAX variants were recognized specifically by the host immune system and antigenicity appeared to be associated with amino-acid sequence variability. Thus, antigenic diversity of MAX and possibly of other arthropod salivary proteins may dictate the development of vector-based vaccines(s).


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  1. Lanzaro GC, Ostrovska K, Herrero MV, Lawyer PG, Warburg A, 1993. Lutzomyia longipalpis is a species complex: genetic divergence and interspecific hybrid sterility among three populations. Am J Trop Med Hyg 48 : 839–847. [Google Scholar]
  2. Ward R, Phillips A, Burnet B, 1986. Genetic isolating mechanisms between different forms of the sandfly Lutzomyia longipalpis (Diptera: Psychodidae). Ann Ist Super Sanita 22 : 69–72. [Google Scholar]
  3. Ribeiro JM, 1987. Role of saliva in blood-feeding by arthropods. Annu Rev Entomol 32 : 463–478. [Google Scholar]
  4. Lerner EA, Shoemaker CB, 1992. Maxadilan. Cloning and functional expression of the gene encoding this potent vasodilator peptide. J Biol Chem 267 : 1062–1066. [Google Scholar]
  5. Lerner EA, Ribeiro JM, Nelson RJ, Lerner MR, 1991. Isolation of maxadilan, a potent vasodilatory peptide from the salivary glands of the sand fly Lutzomyia longipalpis. J Biol Chem 266 : 11234–11236. [Google Scholar]
  6. Kamhawi S, 2000. The biological and immunomodulatory properties of sand fly saliva and its role in the establishment of Leishmania infections. Microbes Infect 2 : 1765–1773. [Google Scholar]
  7. Titus RG, Ribeiro JM, 1988. Salivary gland lysates from the sand fly Lutzomyia longipalpis enhance Leishmania infectivity. Science 239 : 1306–1308. [Google Scholar]
  8. Theodos CM, Titus RG, 1993. Salivary gland material from the sand fly Lutzomyia longipalpis has an inhibitory effect on macrophage function in vitro. Parasite Immunol 15 : 481–487. [Google Scholar]
  9. Qureshi AA, Asahina A, Ohnuma M, Tajima M, Granstein RD, Lerner EA, 1996. Immunomodulatory properties of maxadilan, the vasodilator peptide from sand fly salivary gland extracts. Am J Trop Med Hyg 54 : 665–671. [Google Scholar]
  10. Soares MB, Titus RG, Shoemaker CB, David JR, Bozza M, 1998. The vasoactive peptide maxadilan from sand fly saliva inhibits TNF- alpha and induces IL-6 by mouse macrophages through interaction with the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor. J Immunol 160 : 1811–1816. [Google Scholar]
  11. Bozza M, Soares MB, Bozza PT, Satoskar AR, Diacovo TG, Brombacher F, Titus RG, Shoemaker CB, David JR, 1998. The PACAP-type I receptor agonist maxadilan from sand fly saliva protects mice against lethal endotoxemia by a mechanism partially dependent on IL-10. Eur J Immunol 28 : 3120–3127. [Google Scholar]
  12. Gillespie RD, Mbow ML, Titus RG, 2000. The immunomodulatory factors of bloodfeeding arthropod saliva. Parasite Immunol 22 : 319–331. [Google Scholar]
  13. Morris RV, Shoemaker CB, David JR, Lanzaro GC, Titus RG, 2001. Sandfly maxadilan exacerbates infection with Leishmania major and vaccinating against it protects against L. major infection. J Immunol 167 : 5226–5230. [Google Scholar]
  14. Lanzaro GC, Lopes AH, Ribeiro JM, Shoemaker CB, Warburg A, Soares M, Titus RG, 1999. Variation in the salivary peptide, maxadilan, from species in the Lutzomyia longipalpis complex. Insect Mol Biol 8 : 267–275. [Google Scholar]
  15. Wikel S, 1982. Immune responses to arthropods and their products. Annu Rev Entomol 27 : 21–48. [Google Scholar]
  16. Wikel S, 1996. Host immunity to ticks. Annu Rev Entomol 41 : 1–22. [Google Scholar]
  17. Ghosh KN, Mukhopadhyay J, 1998. The effect of anti-sandfly saliva antibodies on Phlebotomus argentipes and Leishmania donovani. Int J Parasitol 28 : 275–281. [Google Scholar]
  18. Sanders ML, Glass GE, Scott AL, Schwartz BS, 1998. Kinetics and cross-species comparisons of host antibody responses to lone star ticks and American dog ticks (Acari: Ixodidae). J Med Entomol 35 : 849–856. [Google Scholar]
  19. Lane RS, Moss RB, Hsu YP, Wei T, Mesirow ML, Kuo MM, 1999. Anti-arthropod saliva antibodies among residents of a community at high risk for Lyme disease in California. Am J Trop Med Hyg 61 : 850–859. [Google Scholar]
  20. Peng Z, Simons FE, 1997. Cross-reactivity of skin and serum specific IgE responses and allergen analysis for three mosquito species with worldwide distribution. J Allergy Clin Immunol 100 : 192–198. [Google Scholar]
  21. Barral A, Honda E, Caldas A, Costa J, Vinhas V, Rowton ED, Valenzuela JG, Charlab R, Barral-Netto M, Ribeiro JM, 2000. Human immune response to sand fly salivary gland antigens: a useful epidemiological marker? Am J Trop Med Hyg 62 : 740–745. [Google Scholar]
  22. Young DG, Duncan MA, 1994. Guide to the Identification and Geographic Distribution of Lutzomyia Sand Flies in Mexico, the West Indies, Central and South America (Diptera: Psychodidae). Gainesville, FL: Associated Publishers.
  23. Post RJ, Flook PK, Millest AL, 1993. Methods for the preservation of insects for DNA studies. Biochem Syst Ecol 21 : 85–92. [Google Scholar]
  24. Warburg A, Saraiva E, Lanzaro GC, Titus RG, Neva F, 1994. Saliva of Lutzomyia longipalpis sibling species differs in its composition and capacity to enhance leishmaniasis. Philos Trans R Soc Lond B Biol Sci 345 : 223–230. [Google Scholar]
  25. Jameson BA, Wolf H, 1988. The antigenic index: a novel algorithm for predicting antigenic determinants. Comput Appl Biosci 4 : 181–186. [Google Scholar]
  26. Soong L, Duboise SM, Kima P, McMahon-Pratt D, 1995. Leishmania pifanoi amastigote antigens protect mice against cutaneous leishmaniasis. Infect Immun 63 : 3559–3566. [Google Scholar]
  27. Mutebi JP, Alexander B, Sherlock I, Wellington J, Souza AA, Shaw J, Rangel EF, Lanzaro GC, 1999. Breeding structure of the sand fly Lutzomyia longipalpis (Lutz & Neiva) in Brazil. Am J Trop Med Hyg 61 : 149–157. [Google Scholar]
  28. Nevo E, 1978. Genetic variation in natural population: patterns and theory. Theor Popul Biol 13 : 121–177. [Google Scholar]
  29. Endo T, Ikeo K, Gojobori T, 1996. Large-scale search for genes on which positive selection may operate. Mol Biol Evol 13 : 685–690. [Google Scholar]
  30. Zeledon R, Murillo J, Gutierrez H, 1984. Ecology of Lutzomyia longipalpis (Lutz & Neiva, 1912) and possibilities of the existence of visceral leishmaniasis in Costa Rica. Mem Inst Oswaldo Cruz 79 : 455–459. [Google Scholar]
  31. Morrison AC, Ferro C, Tesh RB, 1993. Host preferences of the sand fly Lutzomyia longipalpis at an endemic focus of American visceral leishmaniasis in Colombia. Am J Trop Med Hyg 49 : 68–75. [Google Scholar]
  32. Moro O, Wakita K, Ohnuma M, Denda S, Lerner EA, Tajima M, 1999. Functional characterization of structural alterations in the sequence of the vasodilatory peptide maxadilan yields a pituitary adenylate cyclase-activating peptide type 1 receptor-specific antagonist. J Biol Chem 274 : 23103–23110. [Google Scholar]
  33. Tatsuno I, Uchida D, Tanaka T, Saeki N, Hirai A, Saito Y, Moro O, Tajima M, 2001. Maxadilan specifically interacts with PAC1 receptor, which is a dominant form of PACAP/VIP family receptors in cultured rat cortical neurons. Brain Res 889 : 138–148. [Google Scholar]
  34. Nara PL, 1999. Deceptive imprinting: insights into mechanisms of immune evasion and vaccine development. Adv Vet Res 41 : 115–134. [Google Scholar]
  35. Nara PL, Garrity R, 1998. Deceptive imprinting: a cosmopolitan strategy for complicating vaccination. Vaccine 16 : 1780–1787. [Google Scholar]
  36. Kamhawi S, Belkaid Y, Modi G, Rowton E, Sacks D, 2000. Protection against cutaneous leishmaniasis resulting from bites of uninfected sand flies. Science 290 : 1351–1354. [Google Scholar]
  37. Valenzuela JG, Belkaid Y, Garfield MK, Mendez S, Kamhawi S, Rowton ED, Sacks DL, Ribeiro JM, 2001. Toward a defined anti-Leishmania vaccine targeting vector antigens: characterization of a protective salivary protein. J Exp Med 194 : 331–342. [Google Scholar]

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  • Received : 14 May 2002
  • Accepted : 03 Mar 2003

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