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

A live-attenuated chlamydial vaccine protects against trachoma in nonhuman primates.
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DOI:
10.1084/jem.20111266
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发表时间:
2011-10-24
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Caldwell HD
Caldwell HD
中科院分区:
其他
文献类型:
--
作者:
Kari L;Whitmire WM;Olivares-Zavaleta N;Goheen MM;Taylor LD;Carlson JH;Sturdevant GL;Lu C;Bakios LE;Randall LB;Parnell MJ;Zhong G;Caldwell HD

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In cynomolgus macaques, ocular infection with a live trachoma strain lacking the conserved 7.5-kb plasmid induced no ocular pathology but facilitated solid or partial protection from subsequent infection with a virulent strain of trachoma. 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.
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