Toward a defined anti-Leishmania vaccine targeting vector antigens: characterization of a protective salivary protein.
Leishmania parasites are transmitted to their vertebrate hosts by infected phlebotomine sand fly bites. Sand fly saliva is known to enhance Leishmania infection, while immunity to the saliva protects against infection as determined by coinoculation of parasites with vector salivary gland homogenates (SGHs) or by infected sand fly bites (Kamhawi, S., Y. Belkaid, G. Modi, E. Rowton, and D. Sacks. 2000. Science. 290:1351-1354). We have now characterized nine salivary proteins of Phlebotomus papatasi, the vector of Leishmania major. One of these salivary proteins, extracted from SDS gels and having an apparent mol wt of 15 kD, was able to protect vaccinated mice challenged with parasites plus SGH. A DNA vaccine containing the cDNA for the predominant 15-kD protein (named SP15) provided this same protection. Protection lasted at least 3 mo after immunization. The vaccine produced both intense humoral and delayed-type hypersensitivity (DTH) reactions. B cell-deficient mice immunized with the SP15 plasmid vaccine successfully controlled Leishmania infection when injected with Leishmania plus SGH. These results indicate that DTH response against saliva provides most or all of the protective effects of this vaccine and that salivary gland proteins or their cDNAs are viable vaccine targets against leishmaniasis.
Valenzuela
J G
JG
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Center Dr., Rm. 4/126, Bethesda, MD 20892, USA.
Belkaid
Y
Y
Garfield
M K
MK
Mendez
S
S
Kamhawi
S
S
Rowton
E D
ED
Sacks
D L
DL
Ribeiro
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000302:isolation & purification; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D019476:Insect Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D007303:Insect Vectors / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology; D018320:Leishmania major / Q000276:immunology* / Q000472:pathogenicity; D007896:Leishmaniasis / Q000276:immunology* / Q000517:prevention & control* / Q000635:transmission; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010691:Phlebotomus / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology; D016052:Protozoan Vaccines / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification
D000941:Antigens; D017931:DNA Primers; D019476:Insect Proteins; D016052:Protozoan Vaccines; D012471:Salivary Proteins and Peptides; D019444:Vaccines, DNA