A live-attenuated chlamydial vaccine protects against trachoma in nonhuman primates

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 mac...

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Bibliographic Details
Published in:The Journal of experimental medicine 2011-10, Vol.208 (11), p.2217-2223
Main Authors: Kari, Laszlo, Whitmire, William M, Olivares-Zavaleta, Norma, Goheen, Morgan M, Taylor, Lacey D, Carlson, John H, Sturdevant, Gail L, Lu, Chunxue, Bakios, Lauren E, Randall, Linnell B, Parnell, Michael J, Zhong, Guangming, Caldwell, Harlan D
Format: Article
Language:English
Subjects:
Animals
Brief Definitive Report
Chlamydia trachomatis
Chlamydia trachomatis - genetics
Chlamydia trachomatis - immunology
Chlamydia trachomatis - pathogenicity
Cynomolgus
Histocompatibility Antigens Class II - genetics
Histocompatibility Antigens Class II - immunology
Humans
Macaca
Macaca fascicularis - genetics
Macaca fascicularis - immunology
Major Histocompatibility Complex
Trachoma - epidemiology
Trachoma - microbiology
Trachoma - prevention & control
Vaccines, Attenuated - therapeutic use
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Summary: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20111266