title: A live-attenuated chlamydial vaccine protects against trachoma in nonhuman primates.
abstract: Blinding trachoma is an ancient neglected tropical disease caused by Chlamydia trachomatis for which a vaccine is needed. We describe a live-attenuated vaccine that is safe and efficacious in preventing trachoma in nonhuman primates, a model with excellent predictive value for humans. Cynomolgus macaques infected ocularly with a trachoma strain deficient for the 7.5-kb conserved plasmid presented with short-lived infections that resolved spontaneously without ocular pathology. Multiple infections with the attenuated plasmid-deficient strain produced no inflammatory ocular pathology but induced an anti-chlamydial immune response. Macaques vaccinated with the attenuated strain were either solidly or partially protected after challenge with virulent plasmid-bearing organisms. Partially protected macaques shed markedly less infectious organisms than controls. Immune correlates of protective immunity were not identified, but we did detect a correlation between MHC class II alleles and solid versus partial protection. Epidemiological models of trachoma control indicate that a vaccine with this degree of efficacy would significantly reduce the prevalence of infection and rates of reinfection, known risk factors which drive blinding disease.
authors: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors: Laszlo
authors: L
authors: Kari
authors: William M
authors: WM
authors: Whitmire
authors: Norma
authors: N
authors: Olivares-Zavaleta
authors: Morgan M
authors: MM
authors: Goheen
authors: Lacey D
authors: LD
authors: Taylor
authors: John H
authors: JH
authors: Carlson
authors: Gail L
authors: GL
authors: Sturdevant
authors: Chunxue
authors: C
authors: Lu
authors: Lauren E
authors: LE
authors: Bakios
authors: Linnell B
authors: LB
authors: Randall
authors: Michael J
authors: MJ
authors: Parnell
authors: Guangming
authors: G
authors: Zhong
authors: Harlan D
authors: HD
authors: Caldwell
mesh_terms: D000818:Animals; D002692:Chlamydia trachomatis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D008252:Macaca fascicularis / Q000235:genetics / Q000276:immunology; D008285:Major Histocompatibility Complex; D014141:Trachoma / Q000453:epidemiology / Q000382:microbiology* / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000627:therapeutic use*
chemical_list: D000949:Histocompatibility Antigens Class II; D014613:Vaccines, Attenuated