Everett Webster, Department of Biological Sciences, Mount Holyoke College, 50 College St., South Hadley, MA 01075, USA
Kyra W. Seiger, Department of Biological Sciences, Mount Holyoke College, 50 College St., South Hadley, MA 01075, USA
Susan B. Core, Department of Molecular Genetics and Microbiology, School of Medicine, University of New Mexico, MSC 08-4660, 1 University of New Mexico, Albuquerque, NM 87131, USA
Amanda L. Collar, Department of Molecular Genetics and Microbiology, School of Medicine, University of New Mexico, MSC 08-4660, 1 University of New Mexico, Albuquerque, NM 87131, USA
Hannah Knapp-Broas, Department of Biological Sciences, Mount Holyoke College, 50 College St., South Hadley, MA 01075, USA
June Graham, Department of Biological Sciences, Mount Holyoke College, 50 College St., South Hadley, MA 01075, USA
Muskan Shrestha
Sarah Afzaal, Department of Biological Sciences, Mount Holyoke College, 50 College St., South Hadley, MA 01075, USA
William M. Geisler, Department of Medicine, University of Alabama at Birmingham, 703 19th St. S, ZRB 242, Birmingham, AL 35294, USA
Cosette M. Wheeler, Center for HPV Prevention, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, MSC 08-4640, 1 University of New Mexico, Albuquerque, NM 87131, USA
Bryce Chackerian, Department of Molecular Genetics and Microbiology, School of Medicine, University of New Mexico, MSC 08-4660, 1 University of New Mexico, Albuquerque, NM 87131, USA
Kathryn M. Frietze, Department of Molecular Genetics and Microbiology, School of Medicine, University of New Mexico, MSC 08-4660, 1 University of New Mexico, Albuquerque, NM 87131, USA,Clinical and Translational Science Center, University of New Mexico Health Sciences, MSC 08-4635, 1 University of New Mexico, Albuquerque, NM 87131, US
Rebeccah S. Lijek, Department of Biological Sciences, Mount Holyoke College, 50 College St., South Hadley, MA 01075, USA

Document Type

Article

Publication Date

1-12-2022

Abstract

An effective vaccine against Chlamydia trachomatis is urgently needed as infection rates continue to rise and C. trachomatis causes reproductive morbidity. An obligate intracellular pathogen, C. trachomatis employs a type 3 secretion system (T3SS) for host cell entry. The tip of the injectosome is composed of the protein CT584, which represents a potential target for neutralization with vaccine-induced antibody. Here, we investigate the immunogenicity and efficacy of a vaccine made of CT584 epitopes coupled to a bacteriophage virus-like particle (VLP), a novel platform for Chlamydia vaccines modeled on the success of HPV vaccines. Female mice were immunized intramuscularly, challenged transcervically with C. trachomatis, and assessed for systemic and local antibody responses and bacterial burden in the upper genital tract. Immunization resulted in a 3-log increase in epitope-specific IgG in serum and uterine homogenates and in the detection of epitope-specific IgG in uterine lavage at low levels. By contrast, sera from women infected with C. trachomatis and virgin controls had similarly low titers to CT584 epitopes, suggesting these epitopes are not systemically immunogenic during natural infection but can be rendered immunogenic by the VLP platform. C. trachomatis burden in the upper genital tract of mice varied after active immunization, yet passive protection was achieved when immune sera were pre-incubated with C. trachomatis prior to inoculation into the genital tract. These data demonstrate the potential for antibody against the T3SS to contribute to protection against C. trachomatis and the value of VLPs as a novel platform for C. trachomatis vaccines.

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