Identification of the hemolysis-associated protein 1 as a cross-protective immunogen of Leptospira interrogans by adenovirus-mediated vaccination.
New vaccine strategies are needed for the prevention of leptospirosis, a widespread human and animal disease caused by pathogenic leptospires. Our previous work determined that a protein leptospiral extract conferred cross-protection in a gerbil model of leptospirosis. The 31- to 34-kDa protein fraction of Leptospira interrogans serovar autumnalis was shown sufficient for this purpose. In the present study, N-terminal sequencing of a 32-kDa fraction and Southern blotting of genomic DNA with corresponding degenerated oligonucleotide probes identified two of its constituents: hemolysis-associated protein 1 (Hap1) and the outer membrane Leptospira protein 1 (OmpL1). Adenovirus-mediated Hap1 vaccination induces significant protection against a virulent heterologous Leptospira challenge in gerbils, whereas a similar OmpL1 construct failed to protect the animals. These data indicate that Hap1 could be a good candidate for developing a new generation of vaccines able to induce broad protection against leptospirosis disease.
Branger
C
C
Unité de Bactériologie Médicale et Moléculaire des Leptospires, Ecole Nationale Vétérinaire de Nantes, 44307 Nantes Cedex 03, France.
Sonrier
C
C
Chatrenet
B
B
Klonjkowski
B
B
Ruvoen-Clouet
N
N
Aubert
A
A
André-Fontaine
G
G
Eloit
M
M
D000256:Adenoviridae; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D001428:Bacterial Vaccines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D001483:Base Sequence; D005591:Chemical Fractionation; D003429:Cross Reactions; D004269:DNA, Bacterial; D005822:Genetic Vectors; D005849:Gerbillinae; D006460:Hemolysin Proteins; D006461:Hemolysis; D007921:Leptospira interrogans / Q000276:immunology*; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014895:Weil Disease / Q000517:prevention & control
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D006460:Hemolysin Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C439630:hemolysis-associated protein 1