The Haemophilus ducreyi trimeric autotransporter adhesin DsrA protects against an experimental infection in the swine model of chancroid.
Adherence of pathogens to cellular targets is required to initiate most infections. Defining strategies that interfere with adhesion is therefore important for the development of preventative measures against infectious diseases. As an adhesin to host extracellular matrix proteins and human keratinocytes, the trimeric autotransporter adhesin DsrA, a proven virulence factor of the Gram-negative bacterium Haemophilus ducreyi, is a potential target for vaccine development. A recombinant form of the N-terminal passenger domain of DsrA from H. ducreyi class I strain 35000HP, termed rNT-DsrAI, was tested as a vaccine immunogen in the experimental swine model of H. ducreyi infection. Viable homologous H. ducreyi was not recovered from any animal receiving four doses of rNT-DsrAI administered with Freund's adjuvant at two-week intervals. Control pigs receiving adjuvant only were all infected. All animals receiving the rNT-DsrAI vaccine developed antibody endpoint titers between 3.5 and 5 logs. All rNT-DsrAI antisera bound the surface of the two H. ducreyi strains used to challenge immunized pigs. Purified anti-rNT-DsrAI IgG partially blocked binding of fibrinogen at the surface of viable H. ducreyi. Overall, immunization with the passenger domain of the trimeric autotransporter adhesin DsrA accelerated clearance of H. ducreyi in experimental lesions, possibly by interfering with fibrinogen binding.
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
William G
WG
Fusco
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Neelima R
NR
Choudhary
College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Patty A
PA
Routh
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Melissa S
MS
Ventevogel
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Valerie A
VA
Smith
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Gary G
GG
Koch
College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Glen W
GW
Almond
College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Paul E
PE
Orndorff
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
Gregory D
GD
Sempowski
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: isabelle_leduc@med.unc.edu.
Isabelle
I
Leduc
D018829:Adhesins, Bacterial / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D002602:Chancroid / Q000517:prevention & control*; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000378:metabolism; D006191:Haemophilus ducreyi; D007106:Immune Sera / Q000276:immunology; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D011994:Recombinant Proteins / Q000276:immunology; D034421:Sus scrofa
D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007106:Immune Sera; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D005340:Fibrinogen
Active protection; DsrA; Haemophilus ducreyi; Trimeric autotransporter adhesin