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

被引:132
作者
Kari, Laszlo [1 ]
Whitmire, William M. [1 ]
Olivares-Zavaleta, Norma [1 ]
Goheen, Morgan M. [1 ]
Taylor, Lacey D. [1 ]
Carlson, John H. [1 ]
Sturdevant, Gail L. [1 ]
Lu, Chunxue [3 ,4 ]
Bakios, Lauren E. [1 ]
Randall, Linnell B. [1 ]
Parnell, Michael J. [2 ]
Zhong, Guangming [3 ,4 ]
Caldwell, Harlan D. [1 ]
机构
[1] NIAID, Lab Intracellular Parasites, NIH, Hamilton, MT 59840 USA
[2] NIAID, Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA
[3] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol, San Antonio, TX 78229 USA
[4] Univ Texas Hlth Sci Ctr San Antonio, Dept Immunol, San Antonio, TX 78229 USA
基金
美国国家卫生研究院;
关键词
OUTER-MEMBRANE PROTEIN; IMMUNE-RESPONSE; ANIMAL-MODEL; INFECTION; PLASMID; COMMUNITIES;
D O I
10.1084/jem.20111266
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2217 / 2223
页数:7
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