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| ISV Paper of the Month |
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October 2011 |
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A live-attenuated chlamydial vaccine protects
against trachoma in nonhuman primates |
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Laszlo Kari, William M. Whitmire, Norma Olivares-Zavaleta,
Morgan M. Goheen, Lacey D. Taylor, John H. Carlson, Gail L. Sturdevant, Chunxue
Lu, Lauren E. Bakios, Linnell B. Randall,Michael J. Parnell, Guangming Zhong, and
Harlan D. Caldwell |
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J. Exp. Med. Vol. 208 No. 11, 2217-2223 |
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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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