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Infection and Immunity, January 2000, p. 192-196, Vol. 68, No. 1
0019-9567/0/$04.00+0

Subclinical Chlamydial Infection of the Female Mouse Genital Tract Generates a Potent Protective Immune Response: Implications for Development of Live Attenuated Chlamydial Vaccine Strains

Hua Su,dagger Ronald Messer, William Whitmire, Scott Hughes, and Harlan D. Caldwell*

Laboratory of Intracellular Parasites, Rocky Mountain Laboratory, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840

Received 3 August 1999/Returned for modification 4 October 1999/Accepted 20 October 1999

Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) for which a vaccine is needed. CD4+ T-helper type 1 (Th1) cell-mediated immunity is an important component of protective immunity against murine chlamydial genital infection. Conventional vaccine approaches have not proven effective in eliciting chlamydial-specific CD4 Th1 immunity at the genital mucosa. Thus, it is possible that the development of a highly efficacious vaccine against genital infection will depend on the generation of a live attenuated C. trachomatis vaccine. Attenuated strains of C. trachomatis do not exist, so their potential utility as vaccines cannot be tested in animal models of infection. We have developed a surrogate model to study the effect of chlamydial attenuation on infection and immunity of the female genital tract by treating mice with a subchlamydiacidal concentration of oxytetracycline following vaginal infection. Compared to untreated control mice, antibiotic-treated mice shed significantly fewer infectious organisms (3 log10) from the cervico-vagina, produced a minimal inflammatory response in urogenital tissue, and did not experience infection-related sequelae. Antibiotic-treated mice generated levels of chlamydia-specific antibody and cell-mediated immunity equivalent to those of control mice. Importantly, antibiotic-treated mice were found to be as immune as control untreated mice when rechallenged vaginally. These findings demonstrate that subclinical chlamydial infection of the murine female genital tract is sufficient to stimulate a potent protective immune response. They also present indirect evidence supporting the possible use of live attenuated chlamydial organisms in the development of vaccines against chlamydial STDs.

* Corresponding author. Mailing address: Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratory, 903 South Fourth St., Hamilton, MT 59840. Phone: (406) 363-9333. Fax: (406) 363-9355. E-mail: hcaldwell{at}atlas.niaid.nih.gov.

dagger Present address: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Laboratory of Host Defenses, Tuberculosis Research Section, Rockville, MD 20852.

Infection and Immunity, January 2000, p. 192-196, Vol. 68, No. 1
0019-9567/0/$04.00+0


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