Immunization with chlamydial type III secretion antigens reduces vaginal shedding and prevents fallopian tube pathology following live C. muridarum challenge.
Chlamydia trachomatis infections in women are often asymptomatic and if left untreated can lead to significant late sequelae including pelvic inflammatory disease and tubal factor infertility. Vaccine development efforts over the past three decades have been unproductive and there is no vaccine approved for use in humans. The existence of serologically distinct strains or serovars of C. trachomatis mandates a vaccine that will provide protection against multiple serovars. Chlamydia spp. use a highly conserved type III secretion system (T3SS) composed of both structural and effector proteins which is an essential virulence factor for infection and intracellular replication. In this study we evaluated a novel fusion protein antigen (BD584) which consists of three T3SS proteins from C. trachomatis (CopB, CopD, and CT584) as a potential chlamydial vaccine candidate. Intranasal immunization with BD584 elicited serum neutralizing antibodies that inhibited C. trachomatis infection in vitro. Following intravaginal challenge with C. muridarum, immunized mice had a 95% reduction in chlamydial shedding from the vagina at the peak of infection and cleared the infection sooner than control mice. Immunization with BD584 also reduced the rate of hydrosalpinx by 87.5% compared to control mice. Together, these results suggest that highly conserved proteins of the chlamydial T3SS may represent good candidates for a Chlamydia vaccine.
M. G. DeGroote Institute for Infectious Disease Research, Canada; St. Joseph's Research Institute, St. Joseph's Healthcare, Hamilton, Ontario, Canada.
David C
DC
Bulir
M. G. DeGroote Institute for Infectious Disease Research, Canada; St. Joseph's Research Institute, St. Joseph's Healthcare, Hamilton, Ontario, Canada.
Steven
S
Liang
St. Joseph's Research Institute, St. Joseph's Healthcare, Hamilton, Ontario, Canada.
Amanda
A
Lee
St. Joseph's Research Institute, St. Joseph's Healthcare, Hamilton, Ontario, Canada.
Sylvia
S
Chong
St. Joseph's Research Institute, St. Joseph's Healthcare, Hamilton, Ontario, Canada.
Elizabeth
E
Simms
St. Joseph's Research Institute, St. Joseph's Healthcare, Hamilton, Ontario, Canada.
Christopher
C
Stone
M. G. DeGroote Institute for Infectious Disease Research, Canada; Department of Pathology and Molecular Medicine, McMaster University, Canada.
Charu
C
Kaushic
M. G. DeGroote Institute for Infectious Disease Research, Canada; Department of Pathology and Molecular Medicine, McMaster University, Canada.
Ali
A
Ashkar
M. G. DeGroote Institute for Infectious Disease Research, Canada; Department of Pathology and Molecular Medicine, McMaster University, Canada; St. Joseph's Research Institute, St. Joseph's Healthcare, Hamilton, Ontario, Canada. Electronic address: mahonyj@mcmaster.ca.
James B
JB
Mahony
D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D057138:Bacterial Shedding; D001428:Bacterial Vaccines / Q000276:immunology*; D002690:Chlamydia Infections / Q000517:prevention & control*; D023502:Chlamydia muridarum; D005187:Fallopian Tubes / Q000382:microbiology / Q000473:pathology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D000069296:Type III Secretion Systems / Q000276:immunology*; D014621:Vagina / Q000382:microbiology; D037521:Virulence Factors / Q000276:immunology
D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D000069296:Type III Secretion Systems; D037521:Virulence Factors
Chlamydia animal model; Chlamydia vaccine; Hydrosalpinx; Type III secretion antigen